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[ { "id": "PMID-8640445__text", "type": "abstract", "text": [ "Cell surface binding characteristics correlate with consensus type I interferon enhanced activity.\nThe binding characteristics of a genetically engineered consensus interferon with unusually high biologic activity were compared to the characteristics of recombinant interferon-alpha 2. Both interferon-alpha 2 and the consensus interferon produced typical biphasic Scatchard plots, indicating multiple independent binding sites. The consensus interferon, which exhibited a biologic potency more than 10-fold greater than all other type I interferons, also exhibited binding site affinities greater than those for IFN-alpha 2b. In addition, a larger number of high, and low-affinity cell surface sites were recognized by the consensus interferon, resulting in equivalent numbers of sites at reduced molar concentrations compared to IFN-a2b. Thus, at any given biologic activity, similar numbers of sites were bound by the consensus interferon and IFN-alpha 2, despite differences in their molar concentrations. No differences in internalization kinetics were identified between the two interferons, indicating that the differences in cell surface binding may be sufficient to produce the differences in biologic activity.\n" ], "offsets": [ [ 0, 1221 ] ] } ]

[ { "id": "PMID-8640445_T1", "type": "Cellular_component", "text": [ "Cell surface" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "PMID-8640445_T2", "type": "Cellular_component", "text": [ "cell surface" ], "offsets": [ [ 682, 694 ] ], "normalized": [] }, { "id": "PMID-8640445_T3", "type": "Cellular_component", "text": [ "cell surface" ], "offsets": [ [ 1133, 1145 ] ], "normalized": [] } ]

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[ { "id": "PMC-2988921-caption-02__text", "type": "caption", "text": [ "Selective SMA angiography was performed 5 h from onset. Before therapy, the SMA was completely occluded by an embolus at the proximal portion (a), and after the bolus infusion of urokinase (600,000 IU) into the SMA, peripheral blood flow was improved. However, the thrombus decreased in size, but remained (b). Asterisks indicate thrombus.\n" ], "offsets": [ [ 0, 340 ] ] } ]

[ { "id": "PMC-2988921-caption-02_T1", "type": "Organism_substance", "text": [ "embolus" ], "offsets": [ [ 110, 117 ] ], "normalized": [] }, { "id": "PMC-2988921-caption-02_T3", "type": "Organism_substance", "text": [ "peripheral blood" ], "offsets": [ [ 216, 232 ] ], "normalized": [] }, { "id": "PMC-2988921-caption-02_T4", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 265, 273 ] ], "normalized": [] }, { "id": "PMC-2988921-caption-02_T5", "type": "Pathological_formation", "text": [ "thrombus" ], "offsets": [ [ 330, 338 ] ], "normalized": [] } ]

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[ { "id": "PMID-14613080__text", "type": "abstract", "text": [ "Microvascular density and vascular endothelial growth factor immunoreactivity as predictors of regional lymph node metastasis from betel-associated oral squamous cell carcinoma. \nPURPOSE: Neovascularization has profound effects on tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a mitogen that acts exclusively on endothelial cells. The roles of miscrovascularity density (MVD) and VEGF expression in the progression of oral squamous cell carcinoma (OSCC) have been controversial. The purpose of the present study was to measure the MVD and VEGF expression in a cohort of patients with betel-associated OSCC and to evaluate for possible clinicopathologic correlations. PATIENTS AND METHODS: The paraffin sections from 49 subjects with OSCC were subjected to immunohistochemical studies to measure the highest MVD (h-MVD) and cytoplasmic immunoreactivity of VEGF. The findings in the tissue samples were analyzed with regard to the patients' risk factors and clinical course. RESULTS: The OSCC samples had an average h-MVD score of 27.7/mm(2). VEGF immunoreactivity was positive in 75.5% of samples. Both h-MVD and VEGF immunoreactivity were statistically associated with lymph node metastasis (P =.012 and.037, respectively). A marginally significant association was also noted between the h-MVD and patient survival (P =.056). The age and oral habits of patients, as well as the tumor site and size, did not appear to be correlated with h-MVD or VEGF immunoreactivity. CONCLUSION: The data suggest that both h-MVD and VEGF immunoreactivity may be useful predictors for the progression of a subset of OSCC associated mostly with betel use. Antiangiogenesis therapy might have a role in reducing regional metastasis.\n" ], "offsets": [ [ 0, 1742 ] ] } ]

[ { "id": "PMID-14613080_T1", "type": "Tissue", "text": [ "Microvascular" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-14613080_T3", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 104, 114 ] ], "normalized": [] }, { "id": "PMID-14613080_T4", "type": "Organism_subdivision", "text": [ "betel" ], "offsets": [ [ 131, 136 ] ], "normalized": [] }, { "id": "PMID-14613080_T5", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 148, 176 ] ], "normalized": [] }, { "id": "PMID-14613080_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 231, 236 ] ], "normalized": [] }, { "id": "PMID-14613080_T9", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 340, 357 ] ], "normalized": [] }, { "id": "PMID-14613080_T10", "type": "Tissue", "text": [ "miscrovascularity" ], "offsets": [ [ 372, 389 ] ], "normalized": [] }, { "id": "PMID-14613080_T12", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 446, 474 ] ], "normalized": [] }, { "id": "PMID-14613080_T13", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 476, 480 ] ], "normalized": [] }, { "id": "PMID-14613080_T16", "type": "Organism_subdivision", "text": [ "betel" ], "offsets": [ [ 612, 617 ] ], "normalized": [] }, { "id": "PMID-14613080_T17", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 629, 633 ] ], "normalized": [] }, { "id": "PMID-14613080_T18", "type": "Cancer", "text": [ "paraffin sections" ], "offsets": [ [ 721, 738 ] ], "normalized": [] }, { "id": "PMID-14613080_T20", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 761, 765 ] ], "normalized": [] }, { "id": "PMID-14613080_T21", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 851, 862 ] ], "normalized": [] }, { "id": "PMID-14613080_T23", "type": "Cancer", "text": [ "tissue samples" ], "offsets": [ [ 909, 923 ] ], "normalized": [] }, { "id": "PMID-14613080_T25", "type": "Cancer", "text": [ "OSCC samples" ], "offsets": [ [ 1014, 1026 ] ], "normalized": [] }, { "id": "PMID-14613080_T27", "type": "Cancer", "text": [ "samples" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "PMID-14613080_T29", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1197, 1207 ] ], "normalized": [] }, { "id": "PMID-14613080_T31", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 1366, 1370 ] ], "normalized": [] }, { "id": "PMID-14613080_T33", "type": "Cancer", "text": [ "tumor site" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [] }, { "id": "PMID-14613080_T36", "type": "Cancer", "text": [ "OSCC" ], "offsets": [ [ 1627, 1631 ] ], "normalized": [] }, { "id": "PMID-14613080_T37", "type": "Organism_subdivision", "text": [ "betel" ], "offsets": [ [ 1655, 1660 ] ], "normalized": [] } ]

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[ { "id": "PMID-16720995__text", "type": "abstract", "text": [ "GDP and AGE receptors: mechanisms of peritoneal damage.\nLong-term peritoneal dialysis (PD) is limited by morphological changes of the peritoneal membrane. Structural changes were promoted by toxicity of glucose degradation products (GDPs) which are generated during heat sterilization in peritoneal dialysis fluids (PDFs). Besides their direct toxicity GDPs promote formation of advanced glycation endproducts (AGEs). RAGE (receptor for AGE) is the best characterized signal transduction receptor for AGEs and is expressed on mesothelial cells. The effects of PDFs with different amounts of GDPs were compared on morphological changes in the peritoneal membrane in a RAGE -/- mouse model. It could be demonstrated that RAGE plays a pivotal role in structural damage (e.g. inflammation, neoangiogenesis and fibrosis) of the peritoneal membrane. Further investigations of this pathway with regard to preventing peritoneal fibrosis should be performed to maintain the integrity of the peritoneal membrane in peritoneal dialysis patients.\n" ], "offsets": [ [ 0, 1035 ] ] } ]

[ { "id": "PMID-16720995_T3", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 37, 47 ] ], "normalized": [] }, { "id": "PMID-16720995_T4", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 66, 76 ] ], "normalized": [] }, { "id": "PMID-16720995_T5", "type": "Multi-tissue_structure", "text": [ "peritoneal membrane" ], "offsets": [ [ 134, 153 ] ], "normalized": [] }, { "id": "PMID-16720995_T8", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "PMID-16720995_T15", "type": "Cell", "text": [ "mesothelial cells" ], "offsets": [ [ 526, 543 ] ], "normalized": [] }, { "id": "PMID-16720995_T17", "type": "Multi-tissue_structure", "text": [ "peritoneal membrane" ], "offsets": [ [ 642, 661 ] ], "normalized": [] }, { "id": "PMID-16720995_T21", "type": "Multi-tissue_structure", "text": [ "peritoneal membrane" ], "offsets": [ [ 823, 842 ] ], "normalized": [] }, { "id": "PMID-16720995_T22", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 909, 919 ] ], "normalized": [] }, { "id": "PMID-16720995_T23", "type": "Multi-tissue_structure", "text": [ "peritoneal membrane" ], "offsets": [ [ 982, 1001 ] ], "normalized": [] }, { "id": "PMID-16720995_T24", "type": "Multi-tissue_structure", "text": [ "peritoneal" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] } ]

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[ { "id": "PMID-17145768__text", "type": "abstract", "text": [ "p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. \nMutant mice lacking both cyclin-dependent kinase (CDK) inhibitors p18(Ink4c) and p27(Kip1) develop a tumor spectrum reminiscent of human multiple endocrine neoplasia (MEN) syndromes. To determine how p18 and p27 genetically interact with Men1, the tumor suppressor gene mutated in familial MEN1, we characterized p18-Men1 and p27-Men1 double mutant mice. Compared with their corresponding single mutant littermates, the p18(-/-); Men1(+/-) mice develop tumors at an accelerated rate and with an increased incidence in the pituitary, thyroid, parathyroid, and pancreas. In the pituitary and pancreatic islets, phosphorylation of the retinoblastoma (Rb) protein at both CDK2 and CDK4/6 sites was increased in p18(-/-) and Men1(+/-) cells and was further increased in p18(-/-); Men1(+/-) cells. The remaining wild-type Men1 allele was lost in most tumors from Men1(+/-) mice but was retained in most tumors from p18(-/-); Men1(+/-) mice. Combined mutations of p27(-/-) and Men1(+/-), in contrast, did not exhibit noticeable synergistic stimulation of Rb kinase activity, cell proliferation, and tumor growth. These results demonstrate that functional collaboration exists between p18 and Men1 and suggest that Men1 may regulate additional factor(s) that interact with p18 and p27 differently.\n" ], "offsets": [ [ 0, 1382 ] ] } ]

[ { "id": "PMID-17145768_T4", "type": "Cancer", "text": [ "neuroendocrine organ tumors" ], "offsets": [ [ 62, 89 ] ], "normalized": [] }, { "id": "PMID-17145768_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 193, 198 ] ], "normalized": [] }, { "id": "PMID-17145768_T14", "type": "Cancer", "text": [ "multiple endocrine neoplasia" ], "offsets": [ [ 229, 257 ] ], "normalized": [] }, { "id": "PMID-17145768_T15", "type": "Cancer", "text": [ "MEN" ], "offsets": [ [ 259, 262 ] ], "normalized": [] }, { "id": "PMID-17145768_T19", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 340, 345 ] ], "normalized": [] }, { "id": "PMID-17145768_T20", "type": "Cancer", "text": [ "MEN1" ], "offsets": [ [ 382, 386 ] ], "normalized": [] }, { "id": "PMID-17145768_T30", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 545, 551 ] ], "normalized": [] }, { "id": "PMID-17145768_T31", "type": "Organ", "text": [ "pituitary" ], "offsets": [ [ 614, 623 ] ], "normalized": [] }, { "id": "PMID-17145768_T32", "type": "Organ", "text": [ "thyroid" ], "offsets": [ [ 625, 632 ] ], "normalized": [] }, { "id": "PMID-17145768_T33", "type": "Organ", "text": [ "parathyroid" ], "offsets": [ [ 634, 645 ] ], "normalized": [] }, { "id": "PMID-17145768_T34", "type": "Organ", "text": [ "pancreas" ], "offsets": [ [ 651, 659 ] ], "normalized": [] }, { "id": "PMID-17145768_T35", "type": "Organ", "text": [ "pituitary" ], "offsets": [ [ 668, 677 ] ], "normalized": [] }, { "id": "PMID-17145768_T36", "type": "Multi-tissue_structure", "text": [ "pancreatic islets" ], "offsets": [ [ 682, 699 ] ], "normalized": [] }, { "id": "PMID-17145768_T42", "type": "Cell", "text": [ "p18(-/-) and Men1(+/-) cells" ], "offsets": [ [ 799, 827 ] ], "normalized": [] }, { "id": "PMID-17145768_T45", "type": "Cell", "text": [ "p18(-/-); Men1(+/-) cells" ], "offsets": [ [ 857, 882 ] ], "normalized": [] }, { "id": "PMID-17145768_T48", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 937, 943 ] ], "normalized": [] }, { "id": "PMID-17145768_T51", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 989, 995 ] ], "normalized": [] }, { "id": "PMID-17145768_T58", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1160, 1164 ] ], "normalized": [] }, { "id": "PMID-17145768_T59", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1184, 1189 ] ], "normalized": [] } ]

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[ { "id": "PMID-3930969__text", "type": "abstract", "text": [ "The effect of aflatoxin B1 on the utilization of serum calcium.\nThe mathematical analysis for plasma disappearance curve of aflatoxicosed animals, subsequently injected with 45Ca was determined. The analysis showed that the three main compartments of the calcium pool (plasma, bone and the labile calcium pool on the surface of bone and soft tissues) had been affected. Specifically, the fractional rate constant for migration of 45Ca from plasma pool to the labile pool had been diminished to its third value. This led to a corresponding reduction in the calcium content of the bone ash. The probable mechanism by which aflatoxin B1 affects calcium dynamics may be interpreted by the inhibitory effect of aflatoxin in the hydroxylation mechanism of vitamin D3 into an active intermediate. During aflatoxicosis (induction of 15 days) the animals entered a state of calcium deficiency, secondary to intestinal absorption inhibition. This was followed by bone resorption and disturbance of the fractional removal rate constant among different calcium compartments.\n" ], "offsets": [ [ 0, 1063 ] ] } ]

[ { "id": "PMID-3930969_T1", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 49, 54 ] ], "normalized": [] }, { "id": "PMID-3930969_T2", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 94, 100 ] ], "normalized": [] }, { "id": "PMID-3930969_T3", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 269, 275 ] ], "normalized": [] }, { "id": "PMID-3930969_T4", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 277, 281 ] ], "normalized": [] }, { "id": "PMID-3930969_T5", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 328, 332 ] ], "normalized": [] }, { "id": "PMID-3930969_T6", "type": "Tissue", "text": [ "soft tissues" ], "offsets": [ [ 337, 349 ] ], "normalized": [] }, { "id": "PMID-3930969_T7", "type": "Organism_substance", "text": [ "plasma" ], "offsets": [ [ 440, 446 ] ], "normalized": [] }, { "id": "PMID-3930969_T8", "type": "Organism_substance", "text": [ "bone ash" ], "offsets": [ [ 579, 587 ] ], "normalized": [] }, { "id": "PMID-3930969_T9", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 898, 908 ] ], "normalized": [] }, { "id": "PMID-3930969_T10", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 953, 957 ] ], "normalized": [] }, { "id": "PMID-3930969_T11", "type": "Tissue", "text": [ "surface" ], "offsets": [ [ 317, 324 ] ], "normalized": [] } ]

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[ { "id": "PMC-2211454-sec-18__text", "type": "sec", "text": [ "Acknowledgements\nWe would like to thank our colleague Dr. Nikolaos Papathanasiou for his assistance in performing the statistical analysis.\n" ], "offsets": [ [ 0, 140 ] ] } ]

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[ { "id": "PMID-20549676__text", "type": "abstract", "text": [ "Telomere/telomerase interplay in virus-driven and virus-independent lymphomagenesis: pathogenic and clinical implications. \nTelomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus-related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus-unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase.\n" ], "offsets": [ [ 0, 1431 ] ] } ]

[ { "id": "PMID-20549676_T1", "type": "Cellular_component", "text": [ "Telomere" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "PMID-20549676_T4", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 215, 224 ] ], "normalized": [] }, { "id": "PMID-20549676_T5", "type": "Cell", "text": [ "somatic cells" ], "offsets": [ [ 249, 262 ] ], "normalized": [] }, { "id": "PMID-20549676_T8", "type": "Cell", "text": [ "lymphocytes" ], "offsets": [ [ 332, 343 ] ], "normalized": [] }, { "id": "PMID-20549676_T12", "type": "Cellular_component", "text": [ "telomere" ], "offsets": [ [ 577, 585 ] ], "normalized": [] }, { "id": "PMID-20549676_T17", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 939, 949 ] ], "normalized": [] }, { "id": "PMID-20549676_T18", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 987, 992 ] ], "normalized": [] }, { "id": "PMID-20549676_T19", "type": "Pathological_formation", "text": [ "lymphoid malignancies" ], "offsets": [ [ 1070, 1091 ] ], "normalized": [] }, { "id": "PMID-20549676_T20", "type": "Cellular_component", "text": [ "telomeres" ], "offsets": [ [ 1126, 1135 ] ], "normalized": [] }, { "id": "PMID-20549676_T22", "type": "Cancer", "text": [ "lymphoid tumors" ], "offsets": [ [ 1279, 1294 ] ], "normalized": [] } ]

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[ { "id": "PMID-15464487__text", "type": "abstract", "text": [ "Flow dynamics of the internal thoracic and radial artery T-graft.\nBACKGROUND:\nComplex use of arterial conduits has resurrected concerns about the adequacy of conduit flow. The T-graft is the extreme example of this trend. Our purpose was to identify the limitation of single source inflow and to compare flow capacity with completion coronary flow.\nMETHODS:\nBetween February 1999 and November 2001, 372 patients underwent total arterial revascularization with the T-graft alone. Intraoperative flows were recorded for each limb of the T-graft before and after distal anastomoses in 204 patients. Independent predictors of T-graft flow were identified by multivariate analysis.\nRESULTS:\nFree flow for the radial arterial (RA) limb was 161 +/- 81 mL/min, the internal thoracic artery (ITA) limb 137 +/- 57 mL/min (combined 298 +/- 101 mL/min) versus simultaneous limb flow of 226 +/- 84 mL/min giving a flow restriction of 24% +/- 14%. Completion coronary flow was 88 +/- 49 mL/min for the RA, 60 +/- 45 mL/min for the ITA, and 140 +/- 70 mL/min for both limbs simultaneously to give a flow reserve (vs simultaneous free flow) of 160% or 1.6. Independent predictors of completion RA limb flow are RA proximal diameter (p = 0.005), number of anastomoses (p = 0.018), and target stenosis (p = 0.005).\nCONCLUSIONS:\nA flow reserve of 1.6 compares favorably with an ITA flow reserve of 1.8 at 1-month postoperatively and 1.8 for both the ITA T-graft and the ITA/RA T-graft at 1-week postoperatively as reported by others. Proximal RA diameter and competitive coronary flow influence completion T-graft flow. These data quantitate the limitation of single source inflow of the T-graft configuration and support its continued use.\n" ], "offsets": [ [ 0, 1722 ] ] } ]

[ { "id": "PMID-15464487_T2", "type": "Multi-tissue_structure", "text": [ "arterial conduits" ], "offsets": [ [ 93, 110 ] ], "normalized": [] }, { "id": "PMID-15464487_T3", "type": "Multi-tissue_structure", "text": [ "conduit" ], "offsets": [ [ 158, 165 ] ], "normalized": [] }, { "id": "PMID-15464487_T4", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 334, 342 ] ], "normalized": [] }, { "id": "PMID-15464487_T5", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 428, 436 ] ], "normalized": [] }, { "id": "PMID-15464487_T6", "type": "Multi-tissue_structure", "text": [ "radial arterial (RA) limb" ], "offsets": [ [ 704, 729 ] ], "normalized": [] }, { "id": "PMID-15464487_T7", "type": "Multi-tissue_structure", "text": [ "internal thoracic artery (ITA) limb" ], "offsets": [ [ 757, 792 ] ], "normalized": [] }, { "id": "PMID-15464487_T9", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 945, 953 ] ], "normalized": [] }, { "id": "PMID-15464487_T10", "type": "Multi-tissue_structure", "text": [ "limbs" ], "offsets": [ [ 1053, 1058 ] ], "normalized": [] }, { "id": "PMID-15464487_T11", "type": "Multi-tissue_structure", "text": [ "RA limb" ], "offsets": [ [ 1178, 1185 ] ], "normalized": [] }, { "id": "PMID-15464487_T12", "type": "Multi-tissue_structure", "text": [ "RA" ], "offsets": [ [ 1195, 1197 ] ], "normalized": [] }, { "id": "PMID-15464487_T13", "type": "Multi-tissue_structure", "text": [ "ITA" ], "offsets": [ [ 1359, 1362 ] ], "normalized": [] }, { "id": "PMID-15464487_T14", "type": "Multi-tissue_structure", "text": [ "ITA" ], "offsets": [ [ 1017, 1020 ] ], "normalized": [] }, { "id": "PMID-15464487_T15", "type": "Multi-tissue_structure", "text": [ "RA" ], "offsets": [ [ 988, 990 ] ], "normalized": [] }, { "id": "PMID-15464487_T16", "type": "Multi-tissue_structure", "text": [ "ITA" ], "offsets": [ [ 1431, 1434 ] ], "normalized": [] }, { "id": "PMID-15464487_T17", "type": "Multi-tissue_structure", "text": [ "ITA/RA" ], "offsets": [ [ 1451, 1457 ] ], "normalized": [] }, { "id": "PMID-15464487_T18", "type": "Multi-tissue_structure", "text": [ "RA" ], "offsets": [ [ 1524, 1526 ] ], "normalized": [] }, { "id": "PMID-15464487_T19", "type": "Multi-tissue_structure", "text": [ "coronary" ], "offsets": [ [ 1552, 1560 ] ], "normalized": [] }, { "id": "PMID-15464487_T8", "type": "Multi-tissue_structure", "text": [ "limb" ], "offsets": [ [ 861, 865 ] ], "normalized": [] }, { "id": "PMID-15464487_T1", "type": "Multi-tissue_structure", "text": [ "radial artery" ], "offsets": [ [ 43, 56 ] ], "normalized": [] }, { "id": "PMID-15464487_T22", "type": "Multi-tissue_structure", "text": [ "limb" ], "offsets": [ [ 523, 527 ] ], "normalized": [] }, { "id": "PMID-15464487_T25", "type": "Multi-tissue_structure", "text": [ "internal thoracic" ], "offsets": [ [ 21, 38 ] ], "normalized": [] } ]

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[ { "id": "PMID-899346__text", "type": "abstract", "text": [ "[Considerations regarding two cases of macromastia (author's transl)].\nTwo cases of macromastia have been shown; one which appeared during puberty, the other during menopause. Histopathological examination has demonstrated for the both cases a cystic degeneracy of the glandular tissue with a hyperplazia and hypertrophy of the conjunctive tissue. The pathogeny of macromastia is being discussed and it is demonstrated both the role of hypophysis hormones (prolactine and growth hormone) and of ovarian hormones (estrogens). The treatment was surgical for the both cases.\n" ], "offsets": [ [ 0, 572 ] ] } ]

[ { "id": "PMID-899346_T1", "type": "Tissue", "text": [ "glandular tissue" ], "offsets": [ [ 269, 285 ] ], "normalized": [] }, { "id": "PMID-899346_T2", "type": "Tissue", "text": [ "conjunctive tissue" ], "offsets": [ [ 328, 346 ] ], "normalized": [] }, { "id": "PMID-899346_T3", "type": "Organ", "text": [ "ovarian" ], "offsets": [ [ 495, 502 ] ], "normalized": [] }, { "id": "PMID-899346_T4", "type": "Pathological_formation", "text": [ "cystic" ], "offsets": [ [ 244, 250 ] ], "normalized": [] } ]

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[ { "id": "PMC-2889408-caption-02__text", "type": "caption", "text": [ "The eukaryotic parasite Trypanosoma brucei is able to import inositol from the environment or synthesize it de novo. However, according to the current model, inositol imported from the environment is utilized primarily in bulk phosphatidylinositol (red and yellow phospholipid) production via a phosphatidylinositol synthase (PIS) localized to the Golgi complex. Inositol synthesized de novo is primarily used to generate phosphatidylinositol that is used for production of glycosylphosphatidylinositols (GPIs). The de novo-synthesized inositol is believed to be utilized mostly for GPI production because the IMPase that dephosphorylates inositol 3-phosphate to inositol is localized to the ER, where GPI synthesis occurs. Mutants lacking TbINO1 are inviable because of diminished GPI production.\n" ], "offsets": [ [ 0, 798 ] ] } ]

[ { "id": "PMC-2889408-caption-02_T1", "type": "Cellular_component", "text": [ "Golgi complex" ], "offsets": [ [ 348, 361 ] ], "normalized": [] }, { "id": "PMC-2889408-caption-02_T2", "type": "Cellular_component", "text": [ "ER" ], "offsets": [ [ 692, 694 ] ], "normalized": [] } ]

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[ { "id": "PMID-17483295__text", "type": "abstract", "text": [ "In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma. \nVery low-dose irradiation (2 x 2 Gy) is a new, effective, and safe local treatment for follicular lymphoma. To understand the biologic mechanisms of this extremely effective response, we compared by microarray the gene-expression profile of patients' biopsies taken before and after radiation. In all patients, a major and consistent induction of p53 target genes was seen. p53 targets involved in cell-cycle arrest and apoptosis showed the same mode of regulation, indicating that, in vivo, both are activated simultaneously. p53 up-regulation and p53-mediated proliferation arrest and apoptosis were substantiated using immunohistochemistry, with activation of both the intrinsic and the extrinsic apoptotic pathways. The other induced genes revealed a whole set of biologically meaningful genes related to macrophage activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biologic insights are important arguments to advocate the use of low-dose radiotherapy as an effective palliative treatment for follicular lymphoma. Moreover, this study is the first in vivo report of the radiation-induced p53 apoptotic response in patients and suggests that this apoptotic response is not immunologically silent.\n" ], "offsets": [ [ 0, 1431 ] ] } ]

[ { "id": "PMID-17483295_T2", "type": "Cancer", "text": [ "follicular lymphoma" ], "offsets": [ [ 92, 111 ] ], "normalized": [] }, { "id": "PMID-17483295_T3", "type": "Cancer", "text": [ "follicular lymphoma" ], "offsets": [ [ 201, 220 ] ], "normalized": [] }, { "id": "PMID-17483295_T5", "type": "Cancer", "text": [ "biopsies" ], "offsets": [ [ 365, 373 ] ], "normalized": [] }, { "id": "PMID-17483295_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 512, 516 ] ], "normalized": [] }, { "id": "PMID-17483295_T12", "type": "Cell", "text": [ "macrophage" ], "offsets": [ [ 923, 933 ] ], "normalized": [] }, { "id": "PMID-17483295_T14", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 1062, 1073 ] ], "normalized": [] }, { "id": "PMID-17483295_T15", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1087, 1092 ] ], "normalized": [] }, { "id": "PMID-17483295_T16", "type": "Cancer", "text": [ "follicular lymphoma" ], "offsets": [ [ 1228, 1247 ] ], "normalized": [] } ]

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[ { "id": "PMID-19622586__text", "type": "abstract", "text": [ "EPOX inhibits angiogenesis by degradation of Mcl-1 through ERK inactivation.\nPURPOSE: Antiangiogenic therapy is considered as an effective strategy for controlling the growth and metastasis of tumors. Among a myriad of biological activities described for xanthone derivatives, the anticancer activity is quite remarkable, but the molecular mechanism is not clearly resolved. In the present study, we investigated the antiangiogenic mechanism of 3,6-di(2,3-epoxypropoxy)xanthone (EPOX), a novel Mcl-1 targeting drug. EXPERIMENTAL DESIGN: To evaluate the antiangiogenic activity of EPOX, we did cell viability, cell cycle, tube formation assay in vitro, and Matrigel plug assay in vivo. To evaluate the effect of EPOX on the endothelial signaling pathway, we did immunoblotting, immunoprecipitation, and immunofluorescence analysis. Intracellular glutathione levels were determined with the use of monochlorobimane, a glutathione-specific probe. RESULTS: EPOX induced endothelial cell apoptosis in association with proteasome-dependent Mcl-1 degradation. Down-regulation of Mcl-1 resulted in an increase in Mcl-1-free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis. Additionally, glutathione depletion and extracellular signal-regulated kinase (ERK) inactivation was observed in EPOX-treated cells. Glutathione supplementation reversed the inhibitory effects of EPOX on ERK, which increases the phosphorylation of Mcl-1 at T(163.) Overexpression of mitogen-activated protein/ERK kinase (MEK) partially reversed the effect of EPOX on Mcl-1 dephosphorylation, ubiquitination, and degradation, further implicating ERK in the regulation of Mcl-1 stability. CONCLUSIONS: This study provides evidence that EPOX induces glutathione depletion, ERK inactivation, and Mcl-1 degradation on endothelial cells, which leads to inhibition of angiogenesis. Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesis-related pathologies.\n" ], "offsets": [ [ 0, 2047 ] ] } ]

[ { "id": "PMID-19622586_T4", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 193, 199 ] ], "normalized": [] }, { "id": "PMID-19622586_T6", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 285, 291 ] ], "normalized": [] }, { "id": "PMID-19622586_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 593, 597 ] ], "normalized": [] }, { "id": "PMID-19622586_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMID-19622586_T13", "type": "Tissue", "text": [ "tube" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "PMID-19622586_T15", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 723, 734 ] ], "normalized": [] }, { "id": "PMID-19622586_T16", "type": "Immaterial_anatomical_entity", "text": [ "Intracellular" ], "offsets": [ [ 831, 844 ] ], "normalized": [] }, { "id": "PMID-19622586_T21", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 966, 982 ] ], "normalized": [] }, { "id": "PMID-19622586_T27", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 1162, 1174 ] ], "normalized": [] }, { "id": "PMID-19622586_T32", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1321, 1326 ] ], "normalized": [] }, { "id": "PMID-19622586_T47", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1808, 1825 ] ], "normalized": [] } ]

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[ { "id": "PMC-2024775-sec-01__text", "type": "sec", "text": [ "Images\nFig. 1\nFig. 2\nFig. 3\n" ], "offsets": [ [ 0, 28 ] ] } ]

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[ { "id": "PMID-15623598__text", "type": "abstract", "text": [ "Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. \nPURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively. EXPERIMENTAL DESIGN: In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes' C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP. RESULTS: The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the \"good\" survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001). CONCLUSIONS: This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.\n" ], "offsets": [ [ 0, 1692 ] ] } ]

[ { "id": "PMID-15623598_T1", "type": "Cancer", "text": [ "colorectal cancers" ], "offsets": [ [ 107, 125 ] ], "normalized": [] }, { "id": "PMID-15623598_T2", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 222, 227 ] ], "normalized": [] }, { "id": "PMID-15623598_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 298, 303 ] ], "normalized": [] }, { "id": "PMID-15623598_T4", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 520, 525 ] ], "normalized": [] }, { "id": "PMID-15623598_T16", "type": "Cancer", "text": [ "stage III (Dukes' C) colorectal cancers" ], "offsets": [ [ 892, 931 ] ], "normalized": [] }, { "id": "PMID-15623598_T17", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1038, 1043 ] ], "normalized": [] }, { "id": "PMID-15623598_T18", "type": "Cancer", "text": [ "colorectal cancers" ], "offsets": [ [ 1218, 1236 ] ], "normalized": [] }, { "id": "PMID-15623598_T20", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 1673, 1690 ] ], "normalized": [] }, { "id": "PMID-15623598_T30", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 367, 373 ] ], "normalized": [] } ]

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[ { "id": "PMID-11835401__text", "type": "abstract", "text": [ "Inhibition of PDGF-stimulated and matrix-mediated proliferation of human vascular smooth muscle cells by SPARC is independent of changes in cell shape or cyclin-dependent kinase inhibitors.\nInteractions among growth factors, cells, and extracellular matrix regulate proliferation during normal development and in pathologies such as atherosclerosis. SPARC (secreted protein, acidic, and rich in cysteine) is a matrix-associated glycoprotein that modulates the adhesion and proliferation of vascular cells. In this study, we demonstrate that SPARC inhibits human arterial smooth muscle cell proliferation stimulated by platelet-derived growth factor or by adhesion to monomeric type I collagen. Binding studies with SPARC and SPARC peptides indicate specific and saturable interaction with smooth muscle cells that involves the C-terminal Ca2+-binding region of the protein. We also report that SPARC arrests monomeric collagen-supported smooth muscle cell proliferation in the late G1-phase of the cell cycle in the absence of an effect on cell shape or on levels of cyclin-dependent kinase inhibitors. Cyclin-dependent kinase-2 activity, p107 and cyclin A levels, and retinoblastoma protein phosphorylation are markedly reduced in response to the addition of exogenous SPARC and/or peptides derived from specific domains of SPARC. Thus, SPARC, previously characterized as an inhibitor of platelet-derived growth factor binding to its receptor, also antagonizes smooth muscle cell proliferation mediated by monomeric collagen at the level of cyclin-dependent kinase-2 activity.\n" ], "offsets": [ [ 0, 1578 ] ] } ]

[ { "id": "PMID-11835401_T2", "type": "Cellular_component", "text": [ "matrix" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "PMID-11835401_T4", "type": "Cell", "text": [ "vascular smooth muscle cells" ], "offsets": [ [ 73, 101 ] ], "normalized": [] }, { "id": "PMID-11835401_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 140, 144 ] ], "normalized": [] }, { "id": "PMID-11835401_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 225, 230 ] ], "normalized": [] }, { "id": "PMID-11835401_T9", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 236, 256 ] ], "normalized": [] }, { "id": "PMID-11835401_T12", "type": "Cellular_component", "text": [ "matrix" ], "offsets": [ [ 410, 416 ] ], "normalized": [] }, { "id": "PMID-11835401_T13", "type": "Cell", "text": [ "vascular cells" ], "offsets": [ [ 490, 504 ] ], "normalized": [] }, { "id": "PMID-11835401_T16", "type": "Cell", "text": [ "arterial smooth muscle cell" ], "offsets": [ [ 562, 589 ] ], "normalized": [] }, { "id": "PMID-11835401_T21", "type": "Cell", "text": [ "smooth muscle cells" ], "offsets": [ [ 789, 808 ] ], "normalized": [] }, { "id": "PMID-11835401_T24", "type": "Cell", "text": [ "smooth muscle cell" ], "offsets": [ [ 937, 955 ] ], "normalized": [] }, { "id": "PMID-11835401_T25", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 998, 1002 ] ], "normalized": [] }, { "id": "PMID-11835401_T26", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "PMID-11835401_T36", "type": "Cell", "text": [ "smooth muscle cell" ], "offsets": [ [ 1462, 1480 ] ], "normalized": [] } ]

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[ { "id": "PMID-8398065__text", "type": "abstract", "text": [ "Vitamins regulate gene expression and induce differentiation and growth inhibition in cancer cells. Their relevance in cancer prevention. \nAlthough several hypotheses for human carcinogenesis have been proposed, the specific genetic changes that cause normal cells to become cancer cells have not been identified. In spite of uncertainties regarding the mechanisms of carcinogenesis, several vitamins such as beta-carotene and vitamins A, C, and E, which can reduce the risk of cancer, have been identified, using animal and in vitro models of carcinogenesis. These studies have led to a hypothesis that the supplemental intake of these vitamins may reduce the risk of cancer. This hypothesis in humans can be tested only by intervention trials that are in progress. Prospective and retrospective case-controlled experimental designs are not suitable for testing the above hypothesis. The fact that some vitamins induce cell differentiation and/or growth inhibition in tumor cells in culture suggests that the use of these vitamins in cancer prevention has a cellular basis. In addition to having a direct effect on tumor cells, vitamins such as alpha-tocopheryl succinate and beta-carotene enhance the effect of other agents that induce differentiation in tumor cells. Some vitamins like beta-carotene, retinoic acid, alpha-tocopheryl succinate, and vitamin D also regulate the expressions of certain oncogenes and cellular genes. These are exciting new functions of vitamins that nobody could have predicted only a few years ago.\n" ], "offsets": [ [ 0, 1532 ] ] } ]

[ { "id": "PMID-8398065_T2", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 86, 98 ] ], "normalized": [] }, { "id": "PMID-8398065_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 119, 125 ] ], "normalized": [] }, { "id": "PMID-8398065_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 259, 264 ] ], "normalized": [] }, { "id": "PMID-8398065_T6", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 275, 287 ] ], "normalized": [] }, { "id": "PMID-8398065_T12", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 478, 484 ] ], "normalized": [] }, { "id": "PMID-8398065_T14", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 669, 675 ] ], "normalized": [] }, { "id": "PMID-8398065_T17", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 920, 924 ] ], "normalized": [] }, { "id": "PMID-8398065_T18", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 969, 980 ] ], "normalized": [] }, { "id": "PMID-8398065_T20", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1035, 1041 ] ], "normalized": [] }, { "id": "PMID-8398065_T21", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1059, 1067 ] ], "normalized": [] }, { "id": "PMID-8398065_T22", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1116, 1127 ] ], "normalized": [] }, { "id": "PMID-8398065_T26", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 1257, 1268 ] ], "normalized": [] }, { "id": "PMID-8398065_T32", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1416, 1424 ] ], "normalized": [] } ]

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[ { "id": "PMID-15331370__text", "type": "abstract", "text": [ "Enhanced IGF-1 expression improves smooth muscle cell engraftment after cell transplantation.\nThe functional benefit of cell transplantation after a myocardial infarction is diminished by early cell losses. IGF-1 enhances cell proliferation and survival. We hypothesized that IGF-1-transfected smooth muscle cells (SMCs) would enhance cell survival and improve engraftment after cell transplantation. The IGF-1 gene was transfected into male SMCs and compared with SMCs transfected with a plasmid vector (vector control) and nontransfected SMCs (cell control). IGF-1 mRNA (n=10/group) and protein levels (n=6/group) were higher (P less than 0.05 for all groups) at 3, 7, and 14 days compared with controls. VEGF was also increased in parallel to enhanced IGF-1 expression. IGF-1-transfected cells demonstrated greater cell proliferation, stimulated angiogenesis, and decreased caspase-3 activity after simulated ischemia and reperfusion (P less than 0.05 for all groups compared with vector or cell controls). A uniform left ventricular injury was produced in female rats using a cryoprobe. Three weeks later, 2 x 10(6) cells from three groups were implanted into the scar. One week later, IGF-1-transfected SMCs had increased myocardial IGF-1 and VEGF levels, increased Bcl2 expression, limited cell apoptosis, and enhanced vessel formation in the myocardial scar compared with the two control groups (P less than 0.05 for all groups). The proportion of SMCs surviving in the implanted region was greater (P less than 0.05) in the IGF-1-transfected group than in the vector or cell controls. Gene enhancement with IGF-1 improved donor cell proliferation, survival, and engraftment after cell transplantation, perhaps mediated by enhanced angiogenesis and reduced apoptosis.\n" ], "offsets": [ [ 0, 1779 ] ] } ]

[ { "id": "PMID-15331370_T2", "type": "Cell", "text": [ "smooth muscle cell" ], "offsets": [ [ 35, 53 ] ], "normalized": [] }, { "id": "PMID-15331370_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 72, 76 ] ], "normalized": [] }, { "id": "PMID-15331370_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 120, 124 ] ], "normalized": [] }, { "id": "PMID-15331370_T5", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "PMID-15331370_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 194, 198 ] ], "normalized": [] }, { "id": "PMID-15331370_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 222, 226 ] ], "normalized": [] }, { "id": "PMID-15331370_T10", "type": "Cell", "text": [ "smooth muscle cells" ], "offsets": [ [ 294, 313 ] ], "normalized": [] }, { "id": "PMID-15331370_T11", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 315, 319 ] ], "normalized": [] }, { "id": "PMID-15331370_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "PMID-15331370_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 379, 383 ] ], "normalized": [] }, { "id": "PMID-15331370_T15", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "PMID-15331370_T16", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "PMID-15331370_T17", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 540, 544 ] ], "normalized": [] }, { "id": "PMID-15331370_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 546, 550 ] ], "normalized": [] }, { "id": "PMID-15331370_T23", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 792, 797 ] ], "normalized": [] }, { "id": "PMID-15331370_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 819, 823 ] ], "normalized": [] }, { "id": "PMID-15331370_T26", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 996, 1000 ] ], "normalized": [] }, { "id": "PMID-15331370_T27", "type": "Multi-tissue_structure", "text": [ "left ventricular" ], "offsets": [ [ 1022, 1038 ] ], "normalized": [] }, { "id": "PMID-15331370_T29", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1122, 1127 ] ], "normalized": [] }, { "id": "PMID-15331370_T30", "type": "Pathological_formation", "text": [ "scar" ], "offsets": [ [ 1170, 1174 ] ], "normalized": [] }, { "id": "PMID-15331370_T32", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 1210, 1214 ] ], "normalized": [] }, { "id": "PMID-15331370_T33", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 1229, 1239 ] ], "normalized": [] }, { "id": "PMID-15331370_T37", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1298, 1302 ] ], "normalized": [] }, { "id": "PMID-15331370_T38", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1327, 1333 ] ], "normalized": [] }, { "id": "PMID-15331370_T39", "type": "Pathological_formation", "text": [ "myocardial scar" ], "offsets": [ [ 1351, 1366 ] ], "normalized": [] }, { "id": "PMID-15331370_T40", "type": "Cell", "text": [ "SMCs" ], "offsets": [ [ 1458, 1462 ] ], "normalized": [] }, { "id": "PMID-15331370_T42", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1582, 1586 ] ], "normalized": [] }, { "id": "PMID-15331370_T44", "type": "Cell", "text": [ "donor cell" ], "offsets": [ [ 1634, 1644 ] ], "normalized": [] }, { "id": "PMID-15331370_T45", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1692, 1696 ] ], "normalized": [] }, { "id": "PMID-15331370_T1", "type": "Cellular_component", "text": [ "plasmid" ], "offsets": [ [ 489, 496 ] ], "normalized": [] } ]

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[ { "id": "PMC-2739198-caption-20__text", "type": "caption", "text": [ "Click here for file\n" ], "offsets": [ [ 0, 20 ] ] } ]

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[ { "id": "PMID-16374459__text", "type": "abstract", "text": [ "Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.\nActivation of protein kinase C (PKC) induces phenotypic changes in the morphology of microvascular endothelial cells that affect major functions of the microvasculature. These functions include the first stages of sprouting in angiogenesis, cell migration following wounding, and vascular permeability. The specific isoform(s) of PKC responsible for each of these changes has not been previously identified. In this study, we used two inflammatory agents, IL-1beta and phorbol myristic acetate, to activate PKC isozymes and specific inhibitors of PKCalpha (Go6976) and PKCbeta (hispidin) to distinguish how each of these isoform(s) controls angiogenesis, wound healing, and permeability. In all cases, only inhibition of PKCalpha inhibited each of these functions when compared to the inhibition of PKCbeta. Additional analysis of the mechanism of action of Go6976 (RT-PCR, Western blots, and immunohistochemistry) of the changes in the phosphorylated and nonphosphorylated forms of PKCalpha in the cell membrane and cytoplasm confirmed the specificity of PKCalpha inhibition by Go6976. These studies therefore indicate a specific and a regulatory role of the PKCalpha isoform in three major endothelial cell functions that are important in the maintenance of microvascular homeostasis.\n" ], "offsets": [ [ 0, 1407 ] ] } ]

[ { "id": "PMID-16374459_T1", "type": "Tissue", "text": [ "skin microvasculature" ], "offsets": [ [ 14, 35 ] ], "normalized": [] }, { "id": "PMID-16374459_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 50, 54 ] ], "normalized": [] }, { "id": "PMID-16374459_T6", "type": "Cell", "text": [ "microvascular endothelial cells" ], "offsets": [ [ 205, 236 ] ], "normalized": [] }, { "id": "PMID-16374459_T7", "type": "Tissue", "text": [ "microvasculature" ], "offsets": [ [ 272, 288 ] ], "normalized": [] }, { "id": "PMID-16374459_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 361, 365 ] ], "normalized": [] }, { "id": "PMID-16374459_T9", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 400, 408 ] ], "normalized": [] }, { "id": "PMID-16374459_T18", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 775, 780 ] ], "normalized": [] }, { "id": "PMID-16374459_T23", "type": "Cellular_component", "text": [ "cell membrane" ], "offsets": [ [ 1119, 1132 ] ], "normalized": [] }, { "id": "PMID-16374459_T24", "type": "Organism_substance", "text": [ "cytoplasm" ], "offsets": [ [ 1137, 1146 ] ], "normalized": [] }, { "id": "PMID-16374459_T28", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1312, 1328 ] ], "normalized": [] }, { "id": "PMID-16374459_T29", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 1380, 1393 ] ], "normalized": [] } ]

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[ { "id": "PMC-2782986-sec-02__text", "type": "sec", "text": [ "RESEARCH DESIGN AND METHODS\nFor this study, 20 individuals (mean age 39.5 +/- 11.1 years) with long-standing type 1 diabetes (21.3 +/- 10.7 years) were enrolled in this prospective open-label crossover trial. After achieving optimal blood glucose control, 16 subjects were randomized to exenatide with or without daclizumab. Endogenous insulin production was determined by repeatedly measuring serum C-peptide.\n" ], "offsets": [ [ 0, 411 ] ] } ]

[ { "id": "PMC-2782986-sec-02_T1", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 233, 238 ] ], "normalized": [] }, { "id": "PMC-2782986-sec-02_T2", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 394, 399 ] ], "normalized": [] } ]

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[ { "id": "PMID-16650140__text", "type": "abstract", "text": [ "The ictal bradycardia syndrome: localization and lateralization.\nPURPOSE:\nPrevious studies have established the importance of the insular cortex and temporal lobe in cardiovascular autonomic modulation. Some investigators, based on the results of cortical stimulation response, functional imaging, EEG recordings of seizures, and lesional studies, have suggested that cardiac sympathetic and parasympathetic function may be lateralized, with sympathetic representation lateralized to the right insula, and parasympathetic, to the left. These studies have suggested that ictal bradycardia is most commonly a manifestation of activation of the left temporal and insular cortex. However, the evidence for this is inconsistent. We sought to assess critically the predictable value of ictal bradycardia for seizure localization and lateralization.\nMETHODS:\nIn this study, we reviewed the localization of seizure activity in 13 consecutive patients with ictal bradycardia diagnosed during prolonged video-EEG monitoring at Mayo Clinic Rochester. The localization of electrographic seizure activity at seizure onset and bradycardia onset was identified in all patients. In addition, we performed a comprehensive review of the ictal bradycardia literature focusing on localization of seizure activity in ictal bradycardia cases.\nRESULTS:\nAll occurrences of ictal bradycardia in the 13 identified patients were associated with temporal lobe-onset seizures. However, no consistent lateralization of seizure activity was found at onset of seizure activity or at onset of bradycardia in this population. Seizure activity was bilateral at bradycardia onset in nine of 13 patients. The results from the literature review also showed that a predominance of patients had bilateral activity at bradycardia onset; however, more of the ictal bradycardia cases from the literature had left hemispheric localization of seizure onset.\nCONCLUSIONS:\nIctal bradycardia most often occurs in association with bilateral hemispheric seizure activity and is not a consistent lateralizing sign in localizing seizure onset. Our data do not support the existence of a strictly unilateral parasympathetic cardiomotor representation in the left hemisphere, as has been suggested.\n" ], "offsets": [ [ 0, 2245 ] ] } ]

[ { "id": "PMID-16650140_T1", "type": "Multi-tissue_structure", "text": [ "insular cortex" ], "offsets": [ [ 130, 144 ] ], "normalized": [] }, { "id": "PMID-16650140_T2", "type": "Multi-tissue_structure", "text": [ "temporal lobe" ], "offsets": [ [ 149, 162 ] ], "normalized": [] }, { "id": "PMID-16650140_T3", "type": "Multi-tissue_structure", "text": [ "cortical" ], "offsets": [ [ 247, 255 ] ], "normalized": [] }, { "id": "PMID-16650140_T4", "type": "Multi-tissue_structure", "text": [ "right insula" ], "offsets": [ [ 488, 500 ] ], "normalized": [] }, { "id": "PMID-16650140_T5", "type": "Multi-tissue_structure", "text": [ "left" ], "offsets": [ [ 530, 534 ] ], "normalized": [] }, { "id": "PMID-16650140_T6", "type": "Multi-tissue_structure", "text": [ "left temporal" ], "offsets": [ [ 642, 655 ] ], "normalized": [] }, { "id": "PMID-16650140_T7", "type": "Multi-tissue_structure", "text": [ "insular cortex" ], "offsets": [ [ 660, 674 ] ], "normalized": [] }, { "id": "PMID-16650140_T8", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 166, 180 ] ], "normalized": [] }, { "id": "PMID-16650140_T9", "type": "Multi-tissue_structure", "text": [ "left hemispheric" ], "offsets": [ [ 1865, 1881 ] ], "normalized": [] }, { "id": "PMID-16650140_T10", "type": "Organ", "text": [ "cardiac" ], "offsets": [ [ 368, 375 ] ], "normalized": [] }, { "id": "PMID-16650140_T11", "type": "Multi-tissue_structure", "text": [ "left hemisphere" ], "offsets": [ [ 2205, 2220 ] ], "normalized": [] } ]

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[ { "id": "PMID-14555793__text", "type": "abstract", "text": [ "Therapeutic angiogenesis: a complex problem requiring a sophisticated approach.\nBlood and vascular disorders underlie a plethora of pathologic conditions and are the single most frequent cause of human disease. Ischemia, involving restricted blood flow to tissues is the most common consequence of vessel dysfunction resulting in the disruption of oxygen and nutrient delivery and the accumulation of waste metabolites. Cells cannot survive extended severe ischemia but may be able to adapt to a moderate condition where diffusion to and from bordering nonischemic regions sustains vital functions. Under this condition, the secondary functions of effected cells are likely to be impaired, and a new metabolic equilibrium is established, determined by the level of cross-diffusion and degree of hypoxia. In tissues with a normally high metabolic turnover such as skeletal and cardiac muscle, even mild ischemia causes hypoxia, acidosis, and depressed function (contractility) and eventually threatens myocyte viability and organ function. Ischemic cardiac muscle is additionally vulnerable because reperfusion is essential for survival but reperfusion itself poses additional stress principally from increased production of free radicals during reoxygenation. The latter effect is called reperfusion injury and can cause as much damage as the ischemia. The treatment possibilities for ischemia-related vascular disease are limited. Lipid/cholesterol-lowering agents, diet and antiplatelet adherence (aspirin) therapy may help slow the progression of vessel disease in some instances; but surgical reconstruction may be the only option in advanced stages, and even this is not always an option. An alternative and rather obvious strategy to treat ischemia is to activate endogenous angiogenic or arteriogenic pathways to stimulate revascularization of the tissue. The feasibility of such a strategy has now been established through the results of studies over the past decade, and a new discipline called therapeutic angiogenesis has emerged. This review focuses on the application of therapeutic angiogenesis for treating ischemic muscle disease and includes a critical evaluation of the parameters and limitations of current procedures. The development of this technology has benefited from its application to both peripheral and coronary artery disease and results from both are reviewed here.\n" ], "offsets": [ [ 0, 2396 ] ] } ]

[ { "id": "PMID-14555793_T1", "type": "Organism_substance", "text": [ "Blood" ], "offsets": [ [ 80, 85 ] ], "normalized": [] }, { "id": "PMID-14555793_T2", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 90, 98 ] ], "normalized": [] }, { "id": "PMID-14555793_T4", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 242, 247 ] ], "normalized": [] }, { "id": "PMID-14555793_T5", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 256, 263 ] ], "normalized": [] }, { "id": "PMID-14555793_T6", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 298, 304 ] ], "normalized": [] }, { "id": "PMID-14555793_T8", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-14555793_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 657, 662 ] ], "normalized": [] }, { "id": "PMID-14555793_T10", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 807, 814 ] ], "normalized": [] }, { "id": "PMID-14555793_T11", "type": "Tissue", "text": [ "skeletal" ], "offsets": [ [ 863, 871 ] ], "normalized": [] }, { "id": "PMID-14555793_T12", "type": "Tissue", "text": [ "cardiac muscle" ], "offsets": [ [ 876, 890 ] ], "normalized": [] }, { "id": "PMID-14555793_T13", "type": "Cell", "text": [ "myocyte" ], "offsets": [ [ 1001, 1008 ] ], "normalized": [] }, { "id": "PMID-14555793_T14", "type": "Organ", "text": [ "organ" ], "offsets": [ [ 1023, 1028 ] ], "normalized": [] }, { "id": "PMID-14555793_T15", "type": "Tissue", "text": [ "cardiac muscle" ], "offsets": [ [ 1048, 1062 ] ], "normalized": [] }, { "id": "PMID-14555793_T16", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1402, 1410 ] ], "normalized": [] }, { "id": "PMID-14555793_T19", "type": "Cell", "text": [ "platelet" ], "offsets": [ [ 1480, 1488 ] ], "normalized": [] }, { "id": "PMID-14555793_T21", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1550, 1556 ] ], "normalized": [] }, { "id": "PMID-14555793_T22", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 1855, 1861 ] ], "normalized": [] }, { "id": "PMID-14555793_T23", "type": "Organ", "text": [ "muscle" ], "offsets": [ [ 2131, 2137 ] ], "normalized": [] }, { "id": "PMID-14555793_T24", "type": "Tissue", "text": [ "peripheral" ], "offsets": [ [ 2316, 2326 ] ], "normalized": [] }, { "id": "PMID-14555793_T25", "type": "Multi-tissue_structure", "text": [ "coronary artery" ], "offsets": [ [ 2331, 2346 ] ], "normalized": [] } ]

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[ { "id": "PMC-2690976-sec-05__text", "type": "sec", "text": [ "Efficacy of MMF in current immunosuppressive regimens after kidney transplantation\nCurrent established immunosuppressive strategies in kidney transplantation often include an induction agent (monoclonal or polyclonal anti-T-cell antibodies) based on the immunologic risk of the recipient, followed by a maintenance regimen combining a CNI and an anti-proliferative agent, with or without corticosteroids.2-4 As MMF was the first MPA formulation approved in clinical kidney transplantation, more extensive clinical data are available with this drug in comparison to EC-MPS.\n\n" ], "offsets": [ [ 0, 574 ] ] } ]

[ { "id": "PMC-2690976-sec-05_T1", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 60, 66 ] ], "normalized": [] }, { "id": "PMC-2690976-sec-05_T2", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 135, 141 ] ], "normalized": [] }, { "id": "PMC-2690976-sec-05_T3", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 222, 228 ] ], "normalized": [] }, { "id": "PMC-2690976-sec-05_T4", "type": "Organ", "text": [ "kidney" ], "offsets": [ [ 466, 472 ] ], "normalized": [] } ]

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[ { "id": "PMID-16907772__text", "type": "abstract", "text": [ "Formation of new bone during vertical distraction osteogenesis of the human mandible is related to the presence of blood vessels.\nWe examined the effect of distraction rate on blood vessel growth in intramembraneous ossification after vertical distraction osteogenesis in the human mandible. Six edentulous patients (aged 60+/-9 years) with a severely atrophic mandible underwent bone augmentation with distraction osteogenesis. Two distraction rates (0.5 and 1 mm/day) were compared and for each group three patients were analyzed. Vascular histomorphometry was carried out in two different areas in the distraction gap: (1) in the first and (2) in the second 1 mm area from the osteotomy line, representing the oldest and younger new-bone area, respectively. Correlation analysis was performed between blood vessel parameters and the amount of new bone formed during distraction. Histological analysis demonstrated the presence of blood vessels throughout the soft connective tissue in the distraction gap. The volume density of blood vessels between the two investigated areas was significantly lower in the 1 mm/day groups, suggesting a delay in angiogenesis in this group of patients. A positive correlation between blood vessel volume and bone volume density was found in the younger new-bone area but not in the oldest new-bone area. This correlation was due to a higher number of blood vessels rather than to a larger size of the blood vessels. Our data suggest that the lower blood vessel density found in the patients with 1 mm/day distraction rate may be related to disruption of angiogenesis in the soft connective tissue of the gap or to a less optimal mechanical stimulation of cells involved in angiogenesis. This probably results in the slower rate of osteogenesis seen at the 1 mm/day distraction rate compared with the 0.5 mm/day distraction rate. The data support the concept that a positive relationship exists between the density of blood vessels and the formation of bone. For distraction of the human mandible in elderly patients, a distraction rate of 0.5 mm/day seems beneficial.\n" ], "offsets": [ [ 0, 2105 ] ] } ]

[ { "id": "PMID-16907772_T1", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "PMID-16907772_T3", "type": "Organ", "text": [ "mandible" ], "offsets": [ [ 76, 84 ] ], "normalized": [] }, { "id": "PMID-16907772_T4", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 115, 128 ] ], "normalized": [] }, { "id": "PMID-16907772_T5", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 176, 188 ] ], "normalized": [] }, { "id": "PMID-16907772_T7", "type": "Organ", "text": [ "mandible" ], "offsets": [ [ 282, 290 ] ], "normalized": [] }, { "id": "PMID-16907772_T9", "type": "Organ", "text": [ "mandible" ], "offsets": [ [ 361, 369 ] ], "normalized": [] }, { "id": "PMID-16907772_T10", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 380, 384 ] ], "normalized": [] }, { "id": "PMID-16907772_T12", "type": "Multi-tissue_structure", "text": [ "Vascular" ], "offsets": [ [ 533, 541 ] ], "normalized": [] }, { "id": "PMID-16907772_T13", "type": "Tissue", "text": [ "new-bone area" ], "offsets": [ [ 732, 745 ] ], "normalized": [] }, { "id": "PMID-16907772_T14", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 804, 816 ] ], "normalized": [] }, { "id": "PMID-16907772_T15", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 850, 854 ] ], "normalized": [] }, { "id": "PMID-16907772_T16", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 933, 946 ] ], "normalized": [] }, { "id": "PMID-16907772_T17", "type": "Tissue", "text": [ "soft connective tissue" ], "offsets": [ [ 962, 984 ] ], "normalized": [] }, { "id": "PMID-16907772_T18", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1031, 1044 ] ], "normalized": [] }, { "id": "PMID-16907772_T20", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 1221, 1233 ] ], "normalized": [] }, { "id": "PMID-16907772_T21", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 1245, 1249 ] ], "normalized": [] }, { "id": "PMID-16907772_T22", "type": "Tissue", "text": [ "new-bone area" ], "offsets": [ [ 1290, 1303 ] ], "normalized": [] }, { "id": "PMID-16907772_T23", "type": "Tissue", "text": [ "new-bone area" ], "offsets": [ [ 1326, 1339 ] ], "normalized": [] }, { "id": "PMID-16907772_T24", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1388, 1401 ] ], "normalized": [] }, { "id": "PMID-16907772_T25", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1438, 1451 ] ], "normalized": [] }, { "id": "PMID-16907772_T26", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 1485, 1497 ] ], "normalized": [] }, { "id": "PMID-16907772_T28", "type": "Tissue", "text": [ "soft connective tissue" ], "offsets": [ [ 1611, 1633 ] ], "normalized": [] }, { "id": "PMID-16907772_T29", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1692, 1697 ] ], "normalized": [] }, { "id": "PMID-16907772_T30", "type": "Multi-tissue_structure", "text": [ "blood vessels" ], "offsets": [ [ 1954, 1967 ] ], "normalized": [] }, { "id": "PMID-16907772_T31", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 1989, 1993 ] ], "normalized": [] }, { "id": "PMID-16907772_T33", "type": "Organ", "text": [ "mandible" ], "offsets": [ [ 2024, 2032 ] ], "normalized": [] }, { "id": "PMID-16907772_T2", "type": "Tissue", "text": [ "areas" ], "offsets": [ [ 592, 597 ] ], "normalized": [] }, { "id": "PMID-16907772_T6", "type": "Tissue", "text": [ "area" ], "offsets": [ [ 666, 670 ] ], "normalized": [] } ]

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[ { "id": "PMID-21878661__text", "type": "abstract", "text": [ "Sunitinib induces apoptosis in pheochromocytoma tumor cells by inhibiting VEGFR2/Akt/mTOR/S6K1 pathways through modulation of Bcl-2 and BAD. \nSunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity that mainly targets vascular endothelial growth factor receptors (VEGFRs). Very recently, sunitinib has been shown to be an active agent for the treatment of malignant pheochromocytomas. However, it is unclear whether sunitinib acts only through an antiangiogenic mechanism or whether it may also directly target tumor cells. Sunitinib markedly induced apoptosis of PC12 cells in a dose-dependent and time-dependent manner. Furthermore, in support of these findings, we found that sunitinib induced a reduction in the expression of the antiapoptotic molecule Bcl-2 as well as dephosphorylation of the proapoptotic molecule BAD, which results in the activation of BAD in these cells. Consistent with these apoptotic effects, our results showed that sunitinib inhibited phosphorylation of Akt and mTOR and was followed by a reduction of S6K1, which is a well-known target of mTOR. Knockdown of VEGFR-2 attenuated the sunitinib-induced effects, including apoptosis and inhibition of signaling pathways such as the phosphorylation of Akt as well as mTOR, and Bcl-2, which confirmed that these effects could be mediated by VEGFR-2. In addition, silencing of S6K1 induced apoptosis accompanied by a decrease in the phosphorylation of BAD and Bcl-2, similar to that observed with sunitinib treatment. Thus, these results together suggest that sunitinib initially exerts its apoptotic effect through the inhibition of VEGFR-2, which, when followed by reduction of its downstream effectors, including Akt/mTOR/S6K1, may lead to inhibition of the antiapoptotic molecule Bcl-2 and activation of the proapoptotic molecule BAD in PC12 cells. However, PC12 cells do not precisely reflect the pathogenesis of malignant cells. Therefore, we confirmed the key findings by replicating these experiments in human neuroblastoma SK-N-SH cells.\n" ], "offsets": [ [ 0, 2078 ] ] } ]

[ { "id": "PMID-21878661_T2", "type": "Cell", "text": [ "pheochromocytoma tumor cells" ], "offsets": [ [ 31, 59 ] ], "normalized": [] }, { "id": "PMID-21878661_T10", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 158, 162 ] ], "normalized": [] }, { "id": "PMID-21878661_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 240, 245 ] ], "normalized": [] }, { "id": "PMID-21878661_T15", "type": "Cancer", "text": [ "malignant pheochromocytomas" ], "offsets": [ [ 413, 440 ] ], "normalized": [] }, { "id": "PMID-21878661_T17", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 568, 579 ] ], "normalized": [] }, { "id": "PMID-21878661_T19", "type": "Cell", "text": [ "PC12 cells" ], "offsets": [ [ 621, 631 ] ], "normalized": [] }, { "id": "PMID-21878661_T24", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-21878661_T47", "type": "Cell", "text": [ "PC12 cells" ], "offsets": [ [ 1872, 1882 ] ], "normalized": [] }, { "id": "PMID-21878661_T48", "type": "Cell", "text": [ "PC12 cells" ], "offsets": [ [ 1893, 1903 ] ], "normalized": [] }, { "id": "PMID-21878661_T49", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 1949, 1964 ] ], "normalized": [] }, { "id": "PMID-21878661_T51", "type": "Cell", "text": [ "neuroblastoma SK-N-SH cells" ], "offsets": [ [ 2049, 2076 ] ], "normalized": [] } ]

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[ { "id": "PMID-9088383__text", "type": "abstract", "text": [ "Procedural memory stimulation in Alzheimer's disease: impact of a training programme.\nThe study evaluates the efficacy of a procedural memory stimulation programme in mild and mild-moderate Alzheimer's disease (AD). Twenty basic and instrumental activities of daily living have been selected, and divided into two groups, comparable for difficulty. Ten normal elderly subjects (age 68.0 +/- 4.8 years; MMSE score: 28.7 +/- 0.9; education: 7.6 +/- 3.5 years) were asked to perform the two groups of daily activities and the time required to perform the tasks of each group was recorded and used as a reference. Ten mild and mild-moderate AD patients (age 77.2 +/- 5.3 years; MMSE score: 19.8 +/- 3.5; education: 7.3 +/- 4.7 years) without major behavioural disturbances constituted the experimental group. Patients were evaluated in all 20 daily activities and the time employed was recorded at baseline and after a 3-week training (1 h/d, 5 d/week) period. Five patients were trained during the 3 weeks on half of the 20 daily activities and the other five patients were trained on the remainder. This procedure was adopted in order to detect separately the improvement in \"trained\" and \"not trained\" activities, allowing to control better the effects of the intervention. The assessment of the functional impact of the training was directly measured, through the variation of time employed to perform tasks before and after training. After 3 weeks of training a significant improvement was observed for the trained activities, from 3.6 to 1.9 standard deviations below the performance of the normal elderly controls (P < 0.05). AD patients improved also in not-trained activities from 3.5 to 2.7 standard deviations below the controls' performance (P < 0.05). The rehabilitation of activities of daily living through developing procedural memory strategies may be effective in mild and mild-moderate AD patients.\n" ], "offsets": [ [ 0, 1914 ] ] } ]

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[ { "id": "PMC-2713402-sec-09__text", "type": "sec", "text": [ "Statistical Analysis\nMitochondrial DNA haplogroup frequencies were calculated by counting from the observed genotypes. The Pearson chi-square test and the chi-square test for linear-by-linear association were used to analyze the significances between the prevalence of haplogroups and different age groups. SPSS software (version 10.0) was used.\n" ], "offsets": [ [ 0, 346 ] ] } ]

[ { "id": "PMC-2713402-sec-09_T1", "type": "Cellular_component", "text": [ "Mitochondrial" ], "offsets": [ [ 21, 34 ] ], "normalized": [] } ]

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[ { "id": "PMID-14981916__text", "type": "abstract", "text": [ "Full sequencing analysis of estrogen receptor-alpha gene polymorphism and its association with breast cancer risk.\nBACKGROUND:\nThe estrogen receptor plays a critical role in breast cancer development and progression. So the genetic polymorphism of ER-alpha gene could affect cancer risk and phenotype.\nMATERIALS AND METHODS:\nWe fully sequenced the ER-alpha gene to investigate its single nucleotide polymorphisms (SNPs) in 100 breast cancer patients and 100 controls.\nRESULTS:\nSix novel polymorphism in the control and 11 in cancer patients were found. The G/G genotype at C975 G and A/A genotype at G1782 A had a protective effect against breast cancer when compared to other genotypes (OR = 0.3 and 0.3, respectively). 975G allele was associated inversely with the p53 expression and positively with the bcl-2 expression in cancer with borderline significance. Combining this result with our previous study, these associations became more significant (p = 0.005 and 0.019, respectively).\nCONCLUSION:\nPolymorphisms in ER-alpha gene can affect the breast cancer susceptibility and may be related to other protein expression, such as p53 and bcl-2.\n" ], "offsets": [ [ 0, 1148 ] ] } ]

[ { "id": "PMID-14981916_T1", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 95, 108 ] ], "normalized": [] }, { "id": "PMID-14981916_T2", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 174, 187 ] ], "normalized": [] }, { "id": "PMID-14981916_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 275, 281 ] ], "normalized": [] }, { "id": "PMID-14981916_T4", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 427, 440 ] ], "normalized": [] }, { "id": "PMID-14981916_T5", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 525, 531 ] ], "normalized": [] }, { "id": "PMID-14981916_T6", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 640, 653 ] ], "normalized": [] }, { "id": "PMID-14981916_T7", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 826, 832 ] ], "normalized": [] }, { "id": "PMID-14981916_T8", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 1048, 1061 ] ], "normalized": [] } ]

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[ { "id": "PMID-16204028__text", "type": "abstract", "text": [ "The threshold level of adenomatous polyposis coli protein for mouse intestinal tumorigenesis. \nThe adenomatous polyposis coli (APC) gene, whose mutations are responsible for familial adenomatous polyposis, is a major negative controller of the Wnt/beta-catenin pathway. To investigate the dose-dependent effects of APC protein in suppressing intestinal tumorigenesis, we constructed mutant mice carrying hypomorphic Apc alleles Apc(neoR) and Apc(neoF) whose expression levels were reduced to 20% and 10% of the wild type, respectively. Although both hypomorphic heterozygotes developed intestinal polyps, tumor multiplicities were much lower than that in Apc(Delta716) mice, heterozygotes of an Apc null allele. Like in Apc(Delta716) mice, loss of the wild-type Apc allele was confirmed for all polyps examined in the Apc(neoR) and Apc(neoF) mice. In the embryonic stem cells homozygous for these hypomorphic Apc alleles, the level of the APC protein was inversely correlated with both the beta-catenin accumulation and beta-catenin/T-cell factor transcriptional activity. These results suggest that the reduced APC protein level increases intestinal polyp multiplicity through quantitative stimulation of the beta-catenin/T-cell factor transcription. We further estimated the threshold of APC protein level that forms one polyp per mouse as approximately 15% of the wild type. These results also suggest therapeutic implications concerning Wnt signaling inhibitors.\n" ], "offsets": [ [ 0, 1467 ] ] } ]

[ { "id": "PMID-16204028_T3", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 68, 78 ] ], "normalized": [] }, { "id": "PMID-16204028_T9", "type": "Multi-tissue_structure", "text": [ "intestinal" ], "offsets": [ [ 342, 352 ] ], "normalized": [] }, { "id": "PMID-16204028_T14", "type": "Pathological_formation", "text": [ "intestinal polyps" ], "offsets": [ [ 586, 603 ] ], "normalized": [] }, { "id": "PMID-16204028_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 605, 610 ] ], "normalized": [] }, { "id": "PMID-16204028_T22", "type": "Pathological_formation", "text": [ "polyps" ], "offsets": [ [ 795, 801 ] ], "normalized": [] }, { "id": "PMID-16204028_T26", "type": "Cell", "text": [ "embryonic stem cells" ], "offsets": [ [ 855, 875 ] ], "normalized": [] }, { "id": "PMID-16204028_T33", "type": "Pathological_formation", "text": [ "intestinal polyp" ], "offsets": [ [ 1140, 1156 ] ], "normalized": [] }, { "id": "PMID-16204028_T37", "type": "Pathological_formation", "text": [ "polyp" ], "offsets": [ [ 1323, 1328 ] ], "normalized": [] } ]

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[ { "id": "PMC-2646243-sec-01__text", "type": "sec", "text": [ "Background\n\n" ], "offsets": [ [ 0, 12 ] ] } ]

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[ { "id": "PMID-21196400__text", "type": "abstract", "text": [ "MTSS1: a multifunctional protein and its role in cancer invasion and metastasis. \nMTSS1 (metastasis suppressor-1) was first identified as a metastasis suppressor missing in metastatic bladder carcinoma cell lines. The down-regulation of MTSS1 that may be caused by DNA methylation was also observed in many other types of cancer. While accumlating evidence for the function of MTSS1 support the concept that it is unlikely to be a metastasis suppressor, but actually acts as a scaffold protein that interacts with multiple partners to regulate actin dynamics. It has also been demonstrated that MTSS1 is involved in the Shh signaling pathway in the developing hair follicle and in basal cell carcinomas of the skin. Such evidence indicates that MTSS1 as a multiple functional molecular player and has an important role in development, carcinogenesis and metastasis. However, the biochemical mechanisms by which MTSS1 functions in cells and the physiological role of this protein in animals remain largely unknown. In this review, we will discuss the current knowledge of MTSS1's role in cancer metastasis, carcinogenesis, and development. The clinical significance of MTSS1 will also be discussed.\n" ], "offsets": [ [ 0, 1198 ] ] } ]

[ { "id": "PMID-21196400_T2", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 49, 55 ] ], "normalized": [] }, { "id": "PMID-21196400_T5", "type": "Cell", "text": [ "metastatic bladder carcinoma cell lines" ], "offsets": [ [ 173, 212 ] ], "normalized": [] }, { "id": "PMID-21196400_T8", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 322, 328 ] ], "normalized": [] }, { "id": "PMID-21196400_T13", "type": "Multi-tissue_structure", "text": [ "hair follicle" ], "offsets": [ [ 660, 673 ] ], "normalized": [] }, { "id": "PMID-21196400_T14", "type": "Cancer", "text": [ "basal cell carcinomas" ], "offsets": [ [ 681, 702 ] ], "normalized": [] }, { "id": "PMID-21196400_T15", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 710, 714 ] ], "normalized": [] }, { "id": "PMID-21196400_T18", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 930, 935 ] ], "normalized": [] }, { "id": "PMID-21196400_T20", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1087, 1093 ] ], "normalized": [] } ]

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[ { "id": "PMID-14729736__text", "type": "abstract", "text": [ "Antibiotic-induced persistence of cytotoxic Staphylococcus aureus in non-phagocytic cells.\nOBJECTIVES:\nAfter infection of non-phagocytic cells, some Staphylococcus aureus strains are able to survive and kill their host cells. The purpose of this study was to determine the action of various antibiotics on the survival of host cells and/or intracellular S. aureus.\nMETHODS:\nMurine keratinocyte (PAM212) and fibroblast (mKSA) cell lines were infected with cytotoxic S. aureus and cultured in the presence of various antibiotics at graded concentrations. The viability of host cells was measured 24 h after infection. To determine the bacterial viability within host cells, cellular lysates were prepared and colony forming units were quantified using a spiral plater. Host cells infected with fluorescein isothiocyanate (FITC)-labelled S. aureus were analysed by flow cytometry and microscopy to determine the subcellular localization S. aureus.\nRESULTS:\nOxacillin, vancomycin, gentamicin, ciprofloxacin and trimethoprim/sulfamethoxazole did not rescue host cells from cell death induced by intracellular S. aureus. In contrast, linezolid, rifampicin, azithromycin, clindamycin, erythromycin and quinupristin/dalfopristin suppressed the cytotoxic action of S. aureus. After withdrawal of antibiotics, intracellular S. aureus regained cytotoxic activity and killed their host cells. Only rifampicin was able to eliminate intracellular S. aureus completely within 72 h. In contrast, clindamycin, azithromycin and linezolid induced a state of intracellular persistence of viable S. aureus.\nCONCLUSIONS:\nAntibiotics commonly used for the management of S. aureus infections appear to create a niche for invasive intracellular S. aureus, which may play an important role for persistence and recurrence of infection. Because of its unique ability to eliminate intracellular S. aureus, rifampicin appears to be valuable for the treatment of invasive S. aureus infections.\n" ], "offsets": [ [ 0, 1963 ] ] } ]

[ { "id": "PMID-14729736_T1", "type": "Cell", "text": [ "non-phagocytic cells" ], "offsets": [ [ 69, 89 ] ], "normalized": [] }, { "id": "PMID-14729736_T2", "type": "Cell", "text": [ "non-phagocytic cells" ], "offsets": [ [ 122, 142 ] ], "normalized": [] }, { "id": "PMID-14729736_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 219, 224 ] ], "normalized": [] }, { "id": "PMID-14729736_T4", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 327, 332 ] ], "normalized": [] }, { "id": "PMID-14729736_T5", "type": "Cell", "text": [ "keratinocyte" ], "offsets": [ [ 381, 393 ] ], "normalized": [] }, { "id": "PMID-14729736_T6", "type": "Cell", "text": [ "PAM212" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "PMID-14729736_T8", "type": "Cell", "text": [ "fibroblast (mKSA) cell lines" ], "offsets": [ [ 407, 435 ] ], "normalized": [] }, { "id": "PMID-14729736_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 575, 580 ] ], "normalized": [] }, { "id": "PMID-14729736_T10", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 665, 670 ] ], "normalized": [] }, { "id": "PMID-14729736_T11", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 772, 777 ] ], "normalized": [] }, { "id": "PMID-14729736_T12", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1057, 1062 ] ], "normalized": [] }, { "id": "PMID-14729736_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1068, 1072 ] ], "normalized": [] }, { "id": "PMID-14729736_T14", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1374, 1379 ] ], "normalized": [] }, { "id": "PMID-14729736_T16", "type": "Organism_substance", "text": [ "cellular lysates" ], "offsets": [ [ 672, 688 ] ], "normalized": [] }, { "id": "PMID-14729736_T17", "type": "Cellular_component", "text": [ "subcellular" ], "offsets": [ [ 909, 920 ] ], "normalized": [] }, { "id": "PMID-14729736_T15", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 340, 353 ] ], "normalized": [] }, { "id": "PMID-14729736_T18", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1090, 1103 ] ], "normalized": [] }, { "id": "PMID-14729736_T19", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1300, 1313 ] ], "normalized": [] }, { "id": "PMID-14729736_T20", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1419, 1432 ] ], "normalized": [] }, { "id": "PMID-14729736_T21", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1539, 1552 ] ], "normalized": [] }, { "id": "PMID-14729736_T22", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1706, 1719 ] ], "normalized": [] }, { "id": "PMID-14729736_T23", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1852, 1865 ] ], "normalized": [] }, { "id": "PMID-14729736_T24", "type": "Cell", "text": [ "colony" ], "offsets": [ [ 707, 713 ] ], "normalized": [] }, { "id": "PMID-14729736_T7", "type": "Cell", "text": [ "strains" ], "offsets": [ [ 171, 178 ] ], "normalized": [] } ]

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[ { "id": "PMID-19695243__text", "type": "abstract", "text": [ "Metronomic 5-fluorouracil, oxaliplatin and irinotecan in colorectal cancer.\nMetronomic chemotherapy (the frequent, long term, low dose administration of chemotherapeutic drugs) is a promising therapy because it enhances the anti-endothelial activity of conventional chemotherapeutics, but with lower or no toxic effects compared to maximum tolerated dose administration. The aims of the present study were to compare, in vitro and in vivo, the antiangiogenic and antitumor activities of metronomic irinotecan (CPT-11), oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) in colorectal cancer and to investigate the metronomic combination of these drugs. In vitro cell proliferation, combination studies and vascular endothelial growth factor (VEGF) secretion analyses were performed on endothelial (HMVEC-d) and colorectal cancer (HT-29) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11, L-OHP and 5-FU. HT-29 human colorectal cancer xenograft model was used and tumour growth, microvessel density and VEGF quantification were performed in tumours after the administration of metronomic CPT-11, L-OHP, 5-FU and their simultaneous combination. Low concentrations of SN-38, but not 5-FU and L-OHP, preferentially inhibited endothelial cell proliferation. Simultaneous and continuous exposure of HT-29 and HMVEC-d cells to low concentrations SN-38+L-OHP+5-FU for 144 h showed a strong antagonism and an unfavorable dose-reduction index. Moreover, the ternary combination resulted in a significant increase of VEGF secretion in HT-29 cancer cells. In a xenograft model metronomic CPT-11, but not 5-FU and L-OHP, significantly inhibits HT-29 tumor growth and microvessel density in the absence of toxicity. On the contrary, metronomic 5-FU+L-OHP+CPT-11 therapy did not affect the microvascular count. The metronomic concept might not universally apply to every cytotoxic drug in colorectal cancer and metronomic combination regimens should be used with caution.\n" ], "offsets": [ [ 0, 1997 ] ] } ]

[ { "id": "PMID-19695243_T4", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 57, 74 ] ], "normalized": [] }, { "id": "PMID-19695243_T5", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 229, 240 ] ], "normalized": [] }, { "id": "PMID-19695243_T6", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 467, 472 ] ], "normalized": [] }, { "id": "PMID-19695243_T13", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 568, 585 ] ], "normalized": [] }, { "id": "PMID-19695243_T14", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 657, 661 ] ], "normalized": [] }, { "id": "PMID-19695243_T17", "type": "Cell", "text": [ "endothelial (HMVEC-d)" ], "offsets": [ [ 780, 801 ] ], "normalized": [] }, { "id": "PMID-19695243_T18", "type": "Cell", "text": [ "colorectal cancer (HT-29) cells" ], "offsets": [ [ 806, 837 ] ], "normalized": [] }, { "id": "PMID-19695243_T23", "type": "Cell", "text": [ "HT-29" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "PMID-19695243_T25", "type": "Cancer", "text": [ "colorectal cancer xenograft" ], "offsets": [ [ 956, 983 ] ], "normalized": [] }, { "id": "PMID-19695243_T26", "type": "Cancer", "text": [ "tumour" ], "offsets": [ [ 1003, 1009 ] ], "normalized": [] }, { "id": "PMID-19695243_T27", "type": "Tissue", "text": [ "microvessel" ], "offsets": [ [ 1018, 1029 ] ], "normalized": [] }, { "id": "PMID-19695243_T29", "type": "Cancer", "text": [ "tumours" ], "offsets": [ [ 1080, 1087 ] ], "normalized": [] }, { "id": "PMID-19695243_T36", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1261, 1277 ] ], "normalized": [] }, { "id": "PMID-19695243_T37", "type": "Cell", "text": [ "HT-29" ], "offsets": [ [ 1333, 1338 ] ], "normalized": [] }, { "id": "PMID-19695243_T38", "type": "Cell", "text": [ "HMVEC-d cells" ], "offsets": [ [ 1343, 1356 ] ], "normalized": [] }, { "id": "PMID-19695243_T43", "type": "Cell", "text": [ "HT-29 cancer cells" ], "offsets": [ [ 1564, 1582 ] ], "normalized": [] }, { "id": "PMID-19695243_T44", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 1589, 1598 ] ], "normalized": [] }, { "id": "PMID-19695243_T48", "type": "Cancer", "text": [ "HT-29 tumor" ], "offsets": [ [ 1671, 1682 ] ], "normalized": [] }, { "id": "PMID-19695243_T49", "type": "Tissue", "text": [ "microvessel" ], "offsets": [ [ 1694, 1705 ] ], "normalized": [] }, { "id": "PMID-19695243_T53", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 1815, 1828 ] ], "normalized": [] }, { "id": "PMID-19695243_T54", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 1914, 1931 ] ], "normalized": [] } ]

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[ { "id": "PMID-21743150__text", "type": "abstract", "text": [ "[Expression of Merlin protein in non-small cell lung carcinoma and the clinical significance]. \nOBJECTIVE: To determine the expression and clinical significance of Merlin protein in non-small cell lung cancer (NSCLC). METHODS: The expression of Merlin protein in 45 cases of NSCLC and adjacent tissue of NSCLC and normal lung tissue was checked by immunohistochemistry. The relation between the expression of Merlin protein and the multiple factors of pathological type, gender, P-TNM stage, differentiation and lymph node metastasis was analyzed. RESULTS: The expression rates of Merlin protein in NSCLC and normal lung tissue sections were 73.33% and 15.56%, respectively (P<0.05). The expression of Merlin protein was not associated with the pathological type, gender, P-TNM stage, differentiation and lymph node metastasis (P>0.05). CONCLUSION: Merlin protein might contribute to the initiation of metastasis of NSCLC.\n" ], "offsets": [ [ 0, 923 ] ] } ]

[ { "id": "PMID-21743150_T2", "type": "Cancer", "text": [ "non-small cell lung carcinoma" ], "offsets": [ [ 33, 62 ] ], "normalized": [] }, { "id": "PMID-21743150_T4", "type": "Cancer", "text": [ "non-small cell lung cancer" ], "offsets": [ [ 182, 208 ] ], "normalized": [] }, { "id": "PMID-21743150_T5", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 210, 215 ] ], "normalized": [] }, { "id": "PMID-21743150_T7", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 275, 280 ] ], "normalized": [] }, { "id": "PMID-21743150_T8", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 294, 300 ] ], "normalized": [] }, { "id": "PMID-21743150_T9", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 304, 309 ] ], "normalized": [] }, { "id": "PMID-21743150_T10", "type": "Tissue", "text": [ "lung tissue" ], "offsets": [ [ 321, 332 ] ], "normalized": [] }, { "id": "PMID-21743150_T12", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 512, 522 ] ], "normalized": [] }, { "id": "PMID-21743150_T14", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "PMID-21743150_T15", "type": "Multi-tissue_structure", "text": [ "lung tissue sections" ], "offsets": [ [ 616, 636 ] ], "normalized": [] }, { "id": "PMID-21743150_T17", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 805, 815 ] ], "normalized": [] }, { "id": "PMID-21743150_T19", "type": "Cancer", "text": [ "NSCLC" ], "offsets": [ [ 916, 921 ] ], "normalized": [] } ]

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[ { "id": "PMID-15015551__text", "type": "abstract", "text": [ "Morphogenesis of embryonic CNS vessels.\nThis chapter focuses on the morphology of blood vessel formation in and around the early central nervous system (CNS, i.e., brain and spinal cord) of avian embryos. We discuss cell lineages, proliferation and interactions of endothelial cells, pericytes and smooth muscle cells, and macrophages. Due to space limitations, we can not review the molecular control of CNS angiogenesis, but refer the reader to other chapters in this book and to recent publications on the assembly of the vasculature (1,2).\n" ], "offsets": [ [ 0, 544 ] ] } ]

[ { "id": "PMID-15015551_T1", "type": "Multi-tissue_structure", "text": [ "embryonic CNS vessels" ], "offsets": [ [ 17, 38 ] ], "normalized": [] }, { "id": "PMID-15015551_T2", "type": "Multi-tissue_structure", "text": [ "blood vessel" ], "offsets": [ [ 82, 94 ] ], "normalized": [] }, { "id": "PMID-15015551_T3", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 129, 151 ] ], "normalized": [] }, { "id": "PMID-15015551_T4", "type": "Anatomical_system", "text": [ "CNS" ], "offsets": [ [ 153, 156 ] ], "normalized": [] }, { "id": "PMID-15015551_T5", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 164, 169 ] ], "normalized": [] }, { "id": "PMID-15015551_T6", "type": "Organ", "text": [ "spinal cord" ], "offsets": [ [ 174, 185 ] ], "normalized": [] }, { "id": "PMID-15015551_T8", "type": "Developing_anatomical_structure", "text": [ "embryos" ], "offsets": [ [ 196, 203 ] ], "normalized": [] }, { "id": "PMID-15015551_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "PMID-15015551_T10", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 265, 282 ] ], "normalized": [] }, { "id": "PMID-15015551_T11", "type": "Cell", "text": [ "pericytes" ], "offsets": [ [ 284, 293 ] ], "normalized": [] }, { "id": "PMID-15015551_T12", "type": "Cell", "text": [ "smooth muscle cells" ], "offsets": [ [ 298, 317 ] ], "normalized": [] }, { "id": "PMID-15015551_T13", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 323, 334 ] ], "normalized": [] }, { "id": "PMID-15015551_T14", "type": "Anatomical_system", "text": [ "CNS" ], "offsets": [ [ 405, 408 ] ], "normalized": [] }, { "id": "PMID-15015551_T15", "type": "Multi-tissue_structure", "text": [ "vasculature" ], "offsets": [ [ 525, 536 ] ], "normalized": [] } ]

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[ { "id": "PMID-11957196__text", "type": "abstract", "text": [ "Risk of myelodysplastic syndrome and acute myeloid leukemia in congenital neutropenias. \nGranulocyte colony-stimulating factor (G-CSF) has had a major impact on the management of \"severe chronic neutropenia\" (SCN), a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia and Shwachman-Diamond syndrome (SDS) have developed myelodysplastic syndrome and acute myeloid leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The issue is complicated because both disorders have a propensity for MDS or AML as part of their natural history. To address this, the Severe Chronic Neutropenia International Registry (SCNIR) used its large database of chronic neutropenia patients treated with G-CSF to determine the incidence of malignant myeloid transformation in the two disorders, and its relationship to treatment and to other patient characteristics. No statistically significant relationships were found between age at onset of MDS or AML and patient gender, G-CSF dose, or duration of G-CSF therapy. What was observed, however, was the multistep acquisition of aberrant cellular genetic changes in marrow cells from patients who transformed, including activating ras oncogene mutations, clonal cytogenetic abnormalities, and G-CSF receptor mutations. In murine models, the latter produces a hyperproliferative response to G-CSF, confers resistance to apoptosis, and enhances cell survival. Since congenital neutropenia and SDS are inherited forms of bone marrow failure, G-CSF may accelerate the propensity for MDS/AML in the genetically altered stem and progenitor cells, especially in those with G-CSF receptor and ras mutations (82% and 50% of patients who transform, respectively). Alternatively, and equally plausible, G-CSF may simply be an \"innocent bystander\" that corrects neutropenia, prolongs patient survival, and allows time for the malignant predisposition to declare itself. In patients who transform to overt MDS or AML, hematopoietic stem cell transplantation is the only chance for cure. In those with \"soft\" signs of MDS, such as an isolated clonal cytogenetic change but without other evidence of MDS, or with an isolated G-CSF receptor mutation, there is room for conservative management. One option is to reduce the G-CSF dosage as much as possible, and observe the tempo of progression, if any, to more overt signs of malignancy.\n" ], "offsets": [ [ 0, 2554 ] ] } ]

[ { "id": "PMID-11957196_T1", "type": "Cancer", "text": [ "acute myeloid leukemia" ], "offsets": [ [ 37, 59 ] ], "normalized": [] }, { "id": "PMID-11957196_T6", "type": "Cell", "text": [ "neutrophils" ], "offsets": [ [ 345, 356 ] ], "normalized": [] }, { "id": "PMID-11957196_T7", "type": "Cancer", "text": [ "acute myeloid leukemia" ], "offsets": [ [ 526, 548 ] ], "normalized": [] }, { "id": "PMID-11957196_T8", "type": "Cancer", "text": [ "AML" ], "offsets": [ [ 554, 557 ] ], "normalized": [] }, { "id": "PMID-11957196_T10", "type": "Cancer", "text": [ "AML" ], "offsets": [ [ 701, 704 ] ], "normalized": [] }, { "id": "PMID-11957196_T13", "type": "Cell", "text": [ "malignant myeloid" ], "offsets": [ [ 923, 940 ] ], "normalized": [] }, { "id": "PMID-11957196_T15", "type": "Cancer", "text": [ "AML" ], "offsets": [ [ 1135, 1138 ] ], "normalized": [] }, { "id": "PMID-11957196_T19", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1271, 1279 ] ], "normalized": [] }, { "id": "PMID-11957196_T20", "type": "Cell", "text": [ "marrow cells" ], "offsets": [ [ 1299, 1311 ] ], "normalized": [] }, { "id": "PMID-11957196_T26", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1576, 1580 ] ], "normalized": [] }, { "id": "PMID-11957196_T27", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 1651, 1662 ] ], "normalized": [] }, { "id": "PMID-11957196_T29", "type": "Cancer", "text": [ "AML" ], "offsets": [ [ 1716, 1719 ] ], "normalized": [] }, { "id": "PMID-11957196_T30", "type": "Cell", "text": [ "stem" ], "offsets": [ [ 1747, 1751 ] ], "normalized": [] }, { "id": "PMID-11957196_T31", "type": "Cell", "text": [ "progenitor cells" ], "offsets": [ [ 1756, 1772 ] ], "normalized": [] }, { "id": "PMID-11957196_T38", "type": "Cancer", "text": [ "AML" ], "offsets": [ [ 2133, 2136 ] ], "normalized": [] }, { "id": "PMID-11957196_T39", "type": "Cell", "text": [ "hematopoietic stem cell" ], "offsets": [ [ 2138, 2161 ] ], "normalized": [] }, { "id": "PMID-11957196_T42", "type": "Cancer", "text": [ "malignancy" ], "offsets": [ [ 2542, 2552 ] ], "normalized": [] } ]

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[ { "id": "PMID-12344153__text", "type": "abstract", "text": [ "Act No. 16.045 of 2 June 1989 prohibiting all discrimination that violates the principle of equality of treatment and opportunities for both sexes in all sectors of labor activity.\nThis Uruguayan Act prohibits discrimination in employment with respect to the following areas, among others: 1) advertising for the provision of positions; 2) selection criteria; 3) recruitment and hiring; 4) evaluation of performance criteria; 5) the right to advancement and promotion; 6) labour stability; 7) social benefits; 8) suspension and dismissal, particularly in cases involving a change of civil status, pregnancy, or nursing; 9) possibilities for professional and technical education or retraining; and 10) remuneration criteria. Reserving places for one sex because of the presence of activities in which the sex of the employee is essential for performance or to comply with international labor treaties does not constitute discrimination. Nor do compensatory acts designed to promote equality of opportunities and treatment of both sexes in concrete situations. In cases where the provisions of this Act have been violated, specially designated judges will call the parties together and may adopt measures designed to end the situation complained of. If they deem it necessary, the judges may institute more formal proceedings. If the measures adopted are not carried out, the person violating the law is subject to a daily fine, as well as administrative penalties set out in Act 15.903 of 10 November 1987. Adverse decisions may be appealed. The state is also to undertake educative campaigns to create interest in and understanding of the problems affecting women workers, thus promoting awareness in such workers and their employers of their situation.\n" ], "offsets": [ [ 0, 1760 ] ] } ]

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[ { "id": "PMID-18565374__text", "type": "abstract", "text": [ "Contemporary perspectives on vital pulp therapy: views from the endodontists and pediatric dentists.\nThe purpose of this study was to determine the level of agreement between pediatric dentists and endodontists at a pulp therapy symposium conjointly sponsored by the American Association of Endodontists (AAE) and the American Academy of Pediatric Dentistry (AAPD) on November 2-3, 2007. Presymposium and postsymposium tests were administered, and respondent answers were compared between pediatric dentists and endodontists. Opinions on 3 areas were sought: pulp therapy for cariously involved primary teeth; indirect pulp treatment (IPT) for cariously involved immature permanent teeth; and innovative treatment options including pulpal revascularization and regeneration. Results were analyzed with chi2 tests. Comparisons of presymposium and postsymposium responses and between the 2 groups of attendees indicated that the pediatric dentistry and endodontic communities agree that formocresol will be replaced as a primary tooth pulpotomy agent, that mineral trioxide is the first choice to take its place, that IPT in primary teeth holds hope as a replacement for pulpotomy, and that IPT is an acceptable pulp therapy technique for cariously involved young permanent teeth. Both groups believe that pulp revascularization and regeneration will be viable treatment modalities in the future. The AAE and the AAPD are positioned to begin preparation of best practice guidelines that share common language and treatment recommendations for pulp therapies performed by both specialties.\n" ], "offsets": [ [ 0, 1587 ] ] } ]

[ { "id": "PMID-18565374_T1", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 35, 39 ] ], "normalized": [] }, { "id": "PMID-18565374_T2", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "PMID-18565374_T3", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "PMID-18565374_T4", "type": "Organ", "text": [ "teeth" ], "offsets": [ [ 603, 608 ] ], "normalized": [] }, { "id": "PMID-18565374_T5", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "PMID-18565374_T6", "type": "Organ", "text": [ "teeth" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-18565374_T7", "type": "Tissue", "text": [ "pulpal" ], "offsets": [ [ 732, 738 ] ], "normalized": [] }, { "id": "PMID-18565374_T9", "type": "Organ", "text": [ "tooth" ], "offsets": [ [ 1027, 1032 ] ], "normalized": [] }, { "id": "PMID-18565374_T11", "type": "Organ", "text": [ "teeth" ], "offsets": [ [ 1131, 1136 ] ], "normalized": [] }, { "id": "PMID-18565374_T12", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 1210, 1214 ] ], "normalized": [] }, { "id": "PMID-18565374_T13", "type": "Organ", "text": [ "teeth" ], "offsets": [ [ 1272, 1277 ] ], "normalized": [] }, { "id": "PMID-18565374_T14", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 1304, 1308 ] ], "normalized": [] }, { "id": "PMID-18565374_T15", "type": "Tissue", "text": [ "pulp" ], "offsets": [ [ 1541, 1545 ] ], "normalized": [] }, { "id": "PMID-18565374_T8", "type": "Pathological_formation", "text": [ "cariously" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "PMID-18565374_T10", "type": "Pathological_formation", "text": [ "cariously" ], "offsets": [ [ 644, 653 ] ], "normalized": [] }, { "id": "PMID-18565374_T16", "type": "Pathological_formation", "text": [ "cariously" ], "offsets": [ [ 1237, 1246 ] ], "normalized": [] } ]

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[ { "id": "PMID-18469146__text", "type": "abstract", "text": [ "Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells.\nPhysiological angiogenesis is regulated by various factors, including signaling through vascular endothelial growth factor (VEGF) receptors. We previously reported that a single dose of ethanol (1.4 g/kg), yielding a blood alcohol concentration of 100 mg/dl, significantly impairs angiogenesis in murine wounds, despite adequate levels of VEGF, suggesting direct effects of ethanol on endothelial cell signaling (40). To examine the mechanism by which ethanol influences angiogenesis in wounds, we employed two different in vitro angiogenesis assays to determine whether acute ethanol exposure (100 mg/dl) would have long-lasting effects on VEGF-induced capillary network formation. Ethanol exposure resulted in reduced VEGF-induced cord formation on collagen and reduced capillary network structure on Matrigel in vitro. In addition, ethanol exposure decreased expression of endothelial VEGF receptor-2, as well as VEGF receptor-2 phosphorylation in vitro. Inhibition of ethanol metabolism by 4-methylpyrazole partially abrogated the effect of ethanol on endothelial cell cord formation. However, mice treated with t-butanol, an alcohol not metabolized by alcohol dehydrogenase, exhibited no change in wound vascularity. These results suggest that products of ethanol metabolism are important factors in the development of ethanol-induced changes in endothelial cell responsiveness to VEGF. In vivo, ethanol exposure caused both decreased angiogenesis and increased hypoxia in wounds. Moreover, in vitro experiments demonstrated a direct effect of ethanol on the response to hypoxia in endothelial cells, as ethanol diminished nuclear hypoxia-inducible factor-1alpha protein levels. Together, the data establish that acute ethanol exposure significantly impairs angiogenesis and suggest that this effect is mediated by changes in endothelial cell responsiveness to both VEGF and hypoxia.\n" ], "offsets": [ [ 0, 1972 ] ] } ]

[ { "id": "PMID-18469146_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 46, 50 ] ], "normalized": [] }, { "id": "PMID-18469146_T4", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 64, 81 ] ], "normalized": [] }, { "id": "PMID-18469146_T7", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 300, 305 ] ], "normalized": [] }, { "id": "PMID-18469146_T10", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 387, 393 ] ], "normalized": [] }, { "id": "PMID-18469146_T13", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 468, 484 ] ], "normalized": [] }, { "id": "PMID-18469146_T15", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 570, 576 ] ], "normalized": [] }, { "id": "PMID-18469146_T18", "type": "Multi-tissue_structure", "text": [ "capillary network" ], "offsets": [ [ 737, 754 ] ], "normalized": [] }, { "id": "PMID-18469146_T21", "type": "Tissue", "text": [ "cord" ], "offsets": [ [ 816, 820 ] ], "normalized": [] }, { "id": "PMID-18469146_T23", "type": "Multi-tissue_structure", "text": [ "capillary network" ], "offsets": [ [ 855, 872 ] ], "normalized": [] }, { "id": "PMID-18469146_T25", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 959, 970 ] ], "normalized": [] }, { "id": "PMID-18469146_T31", "type": "Tissue", "text": [ "endothelial cell cord" ], "offsets": [ [ 1139, 1160 ] ], "normalized": [] }, { "id": "PMID-18469146_T36", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 1286, 1291 ] ], "normalized": [] }, { "id": "PMID-18469146_T39", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1434, 1450 ] ], "normalized": [] }, { "id": "PMID-18469146_T42", "type": "Pathological_formation", "text": [ "wounds" ], "offsets": [ [ 1561, 1567 ] ], "normalized": [] }, { "id": "PMID-18469146_T44", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 1670, 1687 ] ], "normalized": [] }, { "id": "PMID-18469146_T48", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1914, 1930 ] ], "normalized": [] }, { "id": "PMID-18469146_T99", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1711, 1718 ] ], "normalized": [] } ]

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[ { "id": "PMID-7684185__text", "type": "abstract", "text": [ "Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.\nDistinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.\n" ], "offsets": [ [ 0, 1603 ] ] } ]

[ { "id": "PMID-7684185_T1", "type": "Cancer", "text": [ "primary" ], "offsets": [ [ 41, 48 ] ], "normalized": [] }, { "id": "PMID-7684185_T2", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 53, 74 ] ], "normalized": [] }, { "id": "PMID-7684185_T3", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "PMID-7684185_T4", "type": "Cancer", "text": [ "primary hepatocellular carcinoma" ], "offsets": [ [ 104, 136 ] ], "normalized": [] }, { "id": "PMID-7684185_T5", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-7684185_T6", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 148, 169 ] ], "normalized": [] }, { "id": "PMID-7684185_T7", "type": "Organ", "text": [ "liver" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "PMID-7684185_T8", "type": "Multi-tissue_structure", "text": [ "biopsy" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "PMID-7684185_T9", "type": "Multi-tissue_structure", "text": [ "specimens" ], "offsets": [ [ 279, 288 ] ], "normalized": [] }, { "id": "PMID-7684185_T10", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 378, 381 ] ], "normalized": [] }, { "id": "PMID-7684185_T11", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 387, 408 ] ], "normalized": [] }, { "id": "PMID-7684185_T12", "type": "Cancer", "text": [ "cholangiocarcinomas" ], "offsets": [ [ 432, 451 ] ], "normalized": [] }, { "id": "PMID-7684185_T13", "type": "Cancer", "text": [ "metastatic adenocarcinomas" ], "offsets": [ [ 460, 486 ] ], "normalized": [] }, { "id": "PMID-7684185_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 615, 620 ] ], "normalized": [] }, { "id": "PMID-7684185_T16", "type": "Tissue", "text": [ "epithelial" ], "offsets": [ [ 656, 666 ] ], "normalized": [] }, { "id": "PMID-7684185_T17", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 676, 684 ] ], "normalized": [] }, { "id": "PMID-7684185_T19", "type": "Cancer", "text": [ "Metastatic adenocarcinomas" ], "offsets": [ [ 827, 853 ] ], "normalized": [] }, { "id": "PMID-7684185_T20", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 1015, 1018 ] ], "normalized": [] }, { "id": "PMID-7684185_T21", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 1179, 1182 ] ], "normalized": [] }, { "id": "PMID-7684185_T22", "type": "Cancer", "text": [ "metastatic adenocarcinomas" ], "offsets": [ [ 1187, 1213 ] ], "normalized": [] }, { "id": "PMID-7684185_T23", "type": "Cancer", "text": [ "HCCs" ], "offsets": [ [ 1220, 1224 ] ], "normalized": [] }, { "id": "PMID-7684185_T24", "type": "Multi-tissue_structure", "text": [ "bile canalicular" ], "offsets": [ [ 1242, 1258 ] ], "normalized": [] }, { "id": "PMID-7684185_T25", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 1331, 1352 ] ], "normalized": [] }, { "id": "PMID-7684185_T26", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 1479, 1482 ] ], "normalized": [] }, { "id": "PMID-7684185_T27", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 1488, 1509 ] ], "normalized": [] }, { "id": "PMID-7684185_T28", "type": "Cancer", "text": [ "cholangiocarcinoma" ], "offsets": [ [ 1516, 1534 ] ], "normalized": [] }, { "id": "PMID-7684185_T29", "type": "Cancer", "text": [ "metastatic carcinomas" ], "offsets": [ [ 1580, 1601 ] ], "normalized": [] }, { "id": "PMID-7684185_T30", "type": "Cancer", "text": [ "HCC" ], "offsets": [ [ 1409, 1412 ] ], "normalized": [] }, { "id": "PMID-7684185_T31", "type": "Cancer", "text": [ "HCCs" ], "offsets": [ [ 424, 428 ] ], "normalized": [] } ]

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[ { "id": "PMID-8874381__text", "type": "abstract", "text": [ "Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo.\nVascular endothelial growth factor (VEGF) is a naturally secreted endothelial cell-specific mitogen. We investigated the hypothesis that naked DNA encoding for VEGF could be used in a strategy of arterial gene therapy to stimulate collateral artery development. Plasmid DNA encoding each of the three principal human VEGF isoforms (phVEGF121, phVEGF165, or phVEGF189) was applied to the hydrogel polymer coating of an angioplasty balloon and delivered percutaneously to one iliac artery of rabbits with operatively induced hindlimb ischemia. Compared with control animals transfected with LacZ, site-specific transfection of phVEGF resulted in augmented collateral vessel development documented by serial angiography, and improvement in calf blood pressure ratio (ischemic to normal limb), resting and maximum blood flow, and capillary to myocyte ratio. Similar results were obtained with phVEGF121, phVEGF165, and phVEGF189, which suggests that these isoforms are biologically equivalent with respect to in vivo angiogenesis. The fact that viral or other adjunctive vectors were not required further suggests that secreted gene products may have potential therapeutic utility even when the number of successfully transfected cells remains low. Arterial gene transfer of naked DNA encoding for a secreted angiogenic cytokine, thus, represents a potential alternative to recombinant protein administration for stimulating collateral vessel development.\n" ], "offsets": [ [ 0, 1588 ] ] } ]

[ { "id": "PMID-8874381_T3", "type": "Multi-tissue_structure", "text": [ "collateral" ], "offsets": [ [ 104, 114 ] ], "normalized": [] }, { "id": "PMID-8874381_T6", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 202, 218 ] ], "normalized": [] }, { "id": "PMID-8874381_T9", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 332, 340 ] ], "normalized": [] }, { "id": "PMID-8874381_T10", "type": "Multi-tissue_structure", "text": [ "collateral artery" ], "offsets": [ [ 367, 384 ] ], "normalized": [] }, { "id": "PMID-8874381_T11", "type": "Cellular_component", "text": [ "Plasmid" ], "offsets": [ [ 398, 405 ] ], "normalized": [] }, { "id": "PMID-8874381_T17", "type": "Multi-tissue_structure", "text": [ "iliac artery" ], "offsets": [ [ 610, 622 ] ], "normalized": [] }, { "id": "PMID-8874381_T19", "type": "Organism_subdivision", "text": [ "hindlimb" ], "offsets": [ [ 659, 667 ] ], "normalized": [] }, { "id": "PMID-8874381_T22", "type": "Multi-tissue_structure", "text": [ "collateral vessel" ], "offsets": [ [ 790, 807 ] ], "normalized": [] }, { "id": "PMID-8874381_T24", "type": "Organism_substance", "text": [ "calf blood" ], "offsets": [ [ 873, 883 ] ], "normalized": [] }, { "id": "PMID-8874381_T26", "type": "Organism_subdivision", "text": [ "limb" ], "offsets": [ [ 919, 923 ] ], "normalized": [] }, { "id": "PMID-8874381_T27", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 946, 951 ] ], "normalized": [] }, { "id": "PMID-8874381_T28", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 962, 971 ] ], "normalized": [] }, { "id": "PMID-8874381_T29", "type": "Cell", "text": [ "myocyte" ], "offsets": [ [ 975, 982 ] ], "normalized": [] }, { "id": "PMID-8874381_T33", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1362, 1367 ] ], "normalized": [] }, { "id": "PMID-8874381_T34", "type": "Multi-tissue_structure", "text": [ "Arterial" ], "offsets": [ [ 1381, 1389 ] ], "normalized": [] }, { "id": "PMID-8874381_T36", "type": "Multi-tissue_structure", "text": [ "collateral vessel" ], "offsets": [ [ 1557, 1574 ] ], "normalized": [] }, { "id": "PMID-8874381_T1", "type": "Immaterial_anatomical_entity", "text": [ "percutaneously" ], "offsets": [ [ 588, 602 ] ], "normalized": [] } ]

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[ { "id": "PMC-2268729-sec-08__text", "type": "sec", "text": [ "Ovariectomy\nBased on the uterine weight, we determined seven unsuccessful OVXs. The rats concerned were removed from further analyses, which left nine rats in the control group, five in the OVX group, seven in the OVX and late ZOL group, and eight in the OVX and early ZOL group. For each animal, we determined the percentage change in structural parameters compared to the values at week 0. Figure 1 shows the average percentage change and upper standard deviation for all groups for BV/TV, Conn.D, SMI, Tb.N, Tb.Th, and Tb.Sp. The OVX group without treatment showed large changes in structural parameters, indicating the development of OVX-induced bone loss (Figs. 1 and 2). Paired Student's t-test indicated significant changes within 2 weeks after OVX for all structural parameters. BV/TV, Conn.D, and Tb.N decreased during the experiment and SMI and Tb.Sp increased. Both Tb.Th and Tb.N decreased within 2 weeks, indicating that both thinning and complete resorption of trabeculae started directly after OVX. The initial rapid loss of bone and connectivity was largely accompanied by trabecular thinning, while secondary, slower loss of bone was concomitant with a decrease in Tb.N. While BV/TV, Conn.D, SMI, Tb.N, and Tb.Sp showed continuous changes in the same direction throughout the experiment, Tb.Th initially decreased significantly until 4 weeks after OVX and then increased again until after 16 weeks Tb.Th was significantly higher than in the control group. \nFig. 1\nAverage percentage change in structural parameters in the metaphyseal proximal tibia and upper standard deviation for all groups at all time points. Brackets indicate P < 0.05 at week 16\nFig. 2\nSame slice of an unprocessed CT scan of the same rat in the OVX group taken at weeks 0 (a), 2 (b), 4 (c), 8 (d), 12 (e), and 16 (f). Images show typical trabecular bone loss due to OVX in the metaphysis. Green line shows the analyzed metaphyseal bone\nThe absolute average values and standard deviations for all structural parameters of all measurements are shown in Table 1. At the starting point, some differences in the values between the groups were present. This was due to the fact that some animals, which mostly had a relatively low BV/TV, were removed from the study because they did not respond to the OVX. However, since we compared the relative changes in each animal, the results were most likely not affected by the difference in absolute values. \nTable 1\nMean values and standard deviation of all structural parameters of all groups at the start of the experiment\nGroup BV/TV (1) Conn.D (1/mm) SMI (1) Tb.N (1/mm) Tb.Th (mum) Tb.Sp (mum)\nControl 0.17 (0.056) 41 (47) 1.52 (0.53) 1.89 (1.38) 105 (49) 613 (368)\nOVX 0.26 (0.055) 141 (76) 1.22 (0.39) 3.77 (1.66) 84 (10) 335 (174)\nOVX + late ZOL 0.23 (0.062) 86 (66) 1.23 (0.34) 2.77 (1.55) 89 (13) 482 (227)\nOVX + early ZOL 0.17 (0.056) 38 (21) 1.70 (0.39) 1.86 (0.80) 95 (7) 647 (207)\n" ], "offsets": [ [ 0, 2923 ] ] } ]

[ { "id": "PMC-2268729-sec-08_T1", "type": "Organ", "text": [ "uterine" ], "offsets": [ [ 25, 32 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T2", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T3", "type": "Organ", "text": [ "trabecular" ], "offsets": [ [ 1089, 1099 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T4", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 1142, 1146 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T5", "type": "Organ", "text": [ "tibia" ], "offsets": [ [ 1560, 1565 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T7", "type": "Tissue", "text": [ "trabecular bone" ], "offsets": [ [ 1828, 1843 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T8", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 1921, 1925 ] ], "normalized": [] }, { "id": "PMC-2268729-sec-08_T6", "type": "Tissue", "text": [ "bone" ], "offsets": [ [ 650, 654 ] ], "normalized": [] } ]

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[ { "id": "PMID-12727857__text", "type": "abstract", "text": [ "Tumor angiogenesis modulates leukocyte-vessel wall interactions in vivo by reducing endothelial adhesion molecule expression.\nThe expression of endothelial cell (EC) adhesion molecules involved in leukocyte-vessel wall interactions is suppressed in malignancies. In the present study, we investigated in vivo the regulation of leukocyte-vessel wall interactions by the presence of a tumor. By means of intravital microscopy, tumor necrosis factor alpha-stimulated leukocyte-vessel wall interactions were studied in ear skin microvessels of nude mice bearing small human LS174T colon carcinomas and in C57Bl/6 mice bearing murine B16F10 melanomas. Leukocyte-vessel wall interactions were studied both within and outside small tumors growing in the ear, and in ear microvessels of mice with a large tumor growing on their flank. Tumor-free mice were used as controls. Compared with values measured at the edge of the ear and in the contralateral ear, leukocyte adhesion was found to be diminished significantly in vessels inside the ear tumor in both mouse models. This reduction disappeared with increasing distance from the tumor. Surprisingly, the level of leukocyte adhesion in ear venules of mice with a large flank tumor was also reduced significantly. Leukocyte rolling, i.e., the step preceding adhesion, was not influenced by the presence of a tumor in nude mice, but was down-regulated in immune-competent C57Bl/6 mice. Treatment of mice bearing a small ear tumor with a humanized antivascular endothelial growth factor antibody prevented the down-regulation of leukocyte-vessel wall interactions inside the tumor vessels compared with the nontreated group. Fluorescence-activated cell sorter analysis showed that isolated tumor ECs have suppressed levels of intercellular adhesion molecule 1 as compared with ECs from normal mouse tissues. In cultured b.END5 cells the tumor necrosis factor alpha-induced up-regulation of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 was reduced in ECs that were preincubated with basic fibroblast growth factor or vascular endothelial growth factor. The current results may have an impact on the effectiveness of clinical immunotherapeutic treatment protocols, because immune effector cells may not be able to enter tumor tissue.\n" ], "offsets": [ [ 0, 2300 ] ] } ]

[ { "id": "PMID-12727857_T1", "type": "Cancer", "text": [ "Tumor" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-12727857_T2", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 29, 38 ] ], "normalized": [] }, { "id": "PMID-12727857_T3", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 39, 50 ] ], "normalized": [] }, { "id": "PMID-12727857_T6", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 197, 206 ] ], "normalized": [] }, { "id": "PMID-12727857_T7", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 207, 218 ] ], "normalized": [] }, { "id": "PMID-12727857_T8", "type": "Cancer", "text": [ "malignancies" ], "offsets": [ [ 249, 261 ] ], "normalized": [] }, { "id": "PMID-12727857_T9", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "PMID-12727857_T10", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 337, 348 ] ], "normalized": [] }, { "id": "PMID-12727857_T11", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 383, 388 ] ], "normalized": [] }, { "id": "PMID-12727857_T13", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 464, 473 ] ], "normalized": [] }, { "id": "PMID-12727857_T14", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 474, 485 ] ], "normalized": [] }, { "id": "PMID-12727857_T15", "type": "Tissue", "text": [ "ear skin microvessels" ], "offsets": [ [ 515, 536 ] ], "normalized": [] }, { "id": "PMID-12727857_T18", "type": "Cancer", "text": [ "LS174T colon carcinomas" ], "offsets": [ [ 570, 593 ] ], "normalized": [] }, { "id": "PMID-12727857_T21", "type": "Cancer", "text": [ "B16F10 melanomas" ], "offsets": [ [ 629, 645 ] ], "normalized": [] }, { "id": "PMID-12727857_T22", "type": "Cell", "text": [ "Leukocyte" ], "offsets": [ [ 647, 656 ] ], "normalized": [] }, { "id": "PMID-12727857_T23", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 657, 668 ] ], "normalized": [] }, { "id": "PMID-12727857_T24", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 725, 731 ] ], "normalized": [] }, { "id": "PMID-12727857_T25", "type": "Organ", "text": [ "ear" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "PMID-12727857_T26", "type": "Tissue", "text": [ "ear microvessels" ], "offsets": [ [ 759, 775 ] ], "normalized": [] }, { "id": "PMID-12727857_T28", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 797, 802 ] ], "normalized": [] }, { "id": "PMID-12727857_T29", "type": "Organism_subdivision", "text": [ "flank" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "PMID-12727857_T30", "type": "Cancer", "text": [ "Tumor" ], "offsets": [ [ 827, 832 ] ], "normalized": [] }, { "id": "PMID-12727857_T32", "type": "Organ", "text": [ "ear" ], "offsets": [ [ 915, 918 ] ], "normalized": [] }, { "id": "PMID-12727857_T33", "type": "Organ", "text": [ "ear" ], "offsets": [ [ 944, 947 ] ], "normalized": [] }, { "id": "PMID-12727857_T34", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 949, 958 ] ], "normalized": [] }, { "id": "PMID-12727857_T35", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 1012, 1019 ] ], "normalized": [] }, { "id": "PMID-12727857_T36", "type": "Cancer", "text": [ "ear tumor" ], "offsets": [ [ 1031, 1040 ] ], "normalized": [] }, { "id": "PMID-12727857_T38", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1124, 1129 ] ], "normalized": [] }, { "id": "PMID-12727857_T39", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 1158, 1167 ] ], "normalized": [] }, { "id": "PMID-12727857_T40", "type": "Multi-tissue_structure", "text": [ "ear venules" ], "offsets": [ [ 1180, 1191 ] ], "normalized": [] }, { "id": "PMID-12727857_T42", "type": "Cancer", "text": [ "flank tumor" ], "offsets": [ [ 1213, 1224 ] ], "normalized": [] }, { "id": "PMID-12727857_T43", "type": "Cell", "text": [ "Leukocyte" ], "offsets": [ [ 1257, 1266 ] ], "normalized": [] }, { "id": "PMID-12727857_T44", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1351, 1356 ] ], "normalized": [] }, { "id": "PMID-12727857_T48", "type": "Cancer", "text": [ "ear tumor" ], "offsets": [ [ 1462, 1471 ] ], "normalized": [] }, { "id": "PMID-12727857_T50", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 1570, 1579 ] ], "normalized": [] }, { "id": "PMID-12727857_T51", "type": "Multi-tissue_structure", "text": [ "vessel wall" ], "offsets": [ [ 1580, 1591 ] ], "normalized": [] }, { "id": "PMID-12727857_T52", "type": "Multi-tissue_structure", "text": [ "tumor vessels" ], "offsets": [ [ 1616, 1629 ] ], "normalized": [] }, { "id": "PMID-12727857_T53", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1689, 1693 ] ], "normalized": [] }, { "id": "PMID-12727857_T54", "type": "Cell", "text": [ "tumor ECs" ], "offsets": [ [ 1731, 1740 ] ], "normalized": [] }, { "id": "PMID-12727857_T56", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 1818, 1821 ] ], "normalized": [] }, { "id": "PMID-12727857_T58", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1840, 1847 ] ], "normalized": [] }, { "id": "PMID-12727857_T59", "type": "Cell", "text": [ "b.END5 cells" ], "offsets": [ [ 1861, 1873 ] ], "normalized": [] }, { "id": "PMID-12727857_T63", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 2018, 2021 ] ], "normalized": [] }, { "id": "PMID-12727857_T66", "type": "Cell", "text": [ "immune effector cells" ], "offsets": [ [ 2239, 2260 ] ], "normalized": [] }, { "id": "PMID-12727857_T67", "type": "Tissue", "text": [ "tumor tissue" ], "offsets": [ [ 2286, 2298 ] ], "normalized": [] }, { "id": "PMID-12727857_T4", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 144, 160 ] ], "normalized": [] }, { "id": "PMID-12727857_T5", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 162, 164 ] ], "normalized": [] } ]

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[ { "id": "PMID-6325250__text", "type": "abstract", "text": [ "Molecular events leading to enhanced glucose transport in Rous sarcoma virus-transformed cells. \nTransformation by Rous sarcoma virus results in a dramatic increase in the rate at which the transformed cells transport glucose across the cell membrane. The increased transport rate is a consequence of an increased number of transporters in the transformed cells. Utilizing antibody raised against the purified human erythrocyte glucose transporter, we have identified the glucose transporter as a membrane glycoprotein with a monomer Mr of approximately 41,000. The increased rate of glucose transport is dependent on the activity of pp60src, the transforming protein of Rous sarcoma virus. This protein has been shown to be a protein kinase that phosphorylates on tyrosine residues. We have examined the tyrosine phosphorylation of a major cellular protein of Mr 36,000 in cells infected with a panel of partially transforming mutants of Rous sarcoma virus. One of these mutants (CU2) increases the rate of glucose transport only slightly and does not render the infected cells fully anchorage independent or tumorigenic (although other transformation parameters are fully induced). Cells infected with this mutant display a 36,000-dalton protein that is phosphorylated to a considerably lesser extent than cells infected with wild-type virus. Analyses of this sort may help to identify the cellular targets of pp60src whose phosphorylation is necessary for the increased glucose transport rate.\n" ], "offsets": [ [ 0, 1497 ] ] } ]

[ { "id": "PMID-6325250_T3", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "PMID-6325250_T5", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 202, 207 ] ], "normalized": [] }, { "id": "PMID-6325250_T7", "type": "Cellular_component", "text": [ "cell membrane" ], "offsets": [ [ 237, 250 ] ], "normalized": [] }, { "id": "PMID-6325250_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 356, 361 ] ], "normalized": [] }, { "id": "PMID-6325250_T10", "type": "Cell", "text": [ "erythrocyte" ], "offsets": [ [ 416, 427 ] ], "normalized": [] }, { "id": "PMID-6325250_T13", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 497, 505 ] ], "normalized": [] }, { "id": "PMID-6325250_T18", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 841, 849 ] ], "normalized": [] }, { "id": "PMID-6325250_T19", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 874, 879 ] ], "normalized": [] }, { "id": "PMID-6325250_T23", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1073, 1078 ] ], "normalized": [] }, { "id": "PMID-6325250_T24", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 1184, 1189 ] ], "normalized": [] }, { "id": "PMID-6325250_T25", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1308, 1313 ] ], "normalized": [] }, { "id": "PMID-6325250_T27", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1392, 1400 ] ], "normalized": [] } ]

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[ { "id": "PMID-19806573__text", "type": "abstract", "text": [ "[Effect of osteopontin silencing by lentivirus-mediated delivery of siRNA on glioma cell invasion and apoptosis]. \nOBJECTIVE: To investigate the effect of osteopontin silencing on the invasion and apoptosis of U251 cells. METHODS: The invasion, apoptosis and levels of uPA, MMP-2 and MMP-9 were determined by invasion assay, flow cytometry, Western blot and real-time fluorescence quantitative PCR respectively. RESULTS: Osteopontin small interference RNA (siRNA) inhibited osteopontin expression and cell invasion, promoted apoptosis in U251 cells. In addition, the expression of Bcl-2, uPA, MMP-2 and MMP-9 was decreased, while Bax level was elevated. CONCLUSION: Osteopontin siRNA can inhibit U251 cells invasion via the down-regulation of uPA, MMP-2 and MMP-9 levels, and promote apoptosis through induction of Bax expression and inhibition of Bcl 2 level. It suggests that osteopontin plays an important role in human glioma progression.\n" ], "offsets": [ [ 0, 943 ] ] } ]

[ { "id": "PMID-19806573_T3", "type": "Cell", "text": [ "glioma cell" ], "offsets": [ [ 77, 88 ] ], "normalized": [] }, { "id": "PMID-19806573_T5", "type": "Cell", "text": [ "U251 cells" ], "offsets": [ [ 210, 220 ] ], "normalized": [] }, { "id": "PMID-19806573_T11", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 501, 505 ] ], "normalized": [] }, { "id": "PMID-19806573_T12", "type": "Cell", "text": [ "U251 cells" ], "offsets": [ [ 538, 548 ] ], "normalized": [] }, { "id": "PMID-19806573_T19", "type": "Cell", "text": [ "U251 cells" ], "offsets": [ [ 696, 706 ] ], "normalized": [] }, { "id": "PMID-19806573_T27", "type": "Cancer", "text": [ "glioma" ], "offsets": [ [ 923, 929 ] ], "normalized": [] } ]

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[ { "id": "PMC-2535566-caption-18__text", "type": "caption", "text": [ "Click here for additional data file.\n" ], "offsets": [ [ 0, 37 ] ] } ]

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[ { "id": "PMID-22172720__text", "type": "abstract", "text": [ "beta-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. \nMalignant melanoma is characterized by frequent metastasis, however, specific changes that regulate this process have not been clearly delineated. Although it is well known that Wnt signaling is frequently dysregulated in melanoma, the functional implications of this observation are unclear. By modulating beta-catenin levels in a mouse model of melanoma that is based on melanocyte-specific Pten loss and Braf(V600E) mutation, we demonstrate that beta-catenin is a central mediator of melanoma metastasis to the lymph nodes and lungs. In addition to altering metastasis, beta-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling. Highly metastatic tumors with beta-catenin stabilization are very similar to a subset of human melanomas. Together these findings establish Wnt signaling as a metastasis regulator in melanoma.\n" ], "offsets": [ [ 0, 955 ] ] } ]

[ { "id": "PMID-22172720_T4", "type": "Cancer", "text": [ "melanomas" ], "offsets": [ [ 76, 85 ] ], "normalized": [] }, { "id": "PMID-22172720_T5", "type": "Cancer", "text": [ "Malignant melanoma" ], "offsets": [ [ 88, 106 ] ], "normalized": [] }, { "id": "PMID-22172720_T7", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 310, 318 ] ], "normalized": [] }, { "id": "PMID-22172720_T10", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 435, 443 ] ], "normalized": [] }, { "id": "PMID-22172720_T11", "type": "Cell", "text": [ "melanocyte" ], "offsets": [ [ 461, 471 ] ], "normalized": [] }, { "id": "PMID-22172720_T16", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 575, 583 ] ], "normalized": [] }, { "id": "PMID-22172720_T17", "type": "Multi-tissue_structure", "text": [ "lymph nodes" ], "offsets": [ [ 602, 613 ] ], "normalized": [] }, { "id": "PMID-22172720_T18", "type": "Organ", "text": [ "lungs" ], "offsets": [ [ 618, 623 ] ], "normalized": [] }, { "id": "PMID-22172720_T20", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 689, 694 ] ], "normalized": [] }, { "id": "PMID-22172720_T25", "type": "Cancer", "text": [ "metastatic tumors" ], "offsets": [ [ 769, 786 ] ], "normalized": [] }, { "id": "PMID-22172720_T28", "type": "Cancer", "text": [ "melanomas" ], "offsets": [ [ 857, 866 ] ], "normalized": [] }, { "id": "PMID-22172720_T30", "type": "Cancer", "text": [ "melanoma" ], "offsets": [ [ 945, 953 ] ], "normalized": [] } ]

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[ { "id": "PMID-21506108__text", "type": "abstract", "text": [ "Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death. \nInhibitor of differentiation-1 (Id-1) is a member of helix-loop-helix (HLH) family of proteins that regulate gene transcription through their inhibitory binding to basic-HLH transcription factors. Similarly to other members of this family, Id-1 is involved in the repression of cell differentiation and activation of cell growth. The dual function of Id-1, inhibition of differentiation, and stimulation of cell proliferation, might be interdependent, as cell differentiation is generally coupled with the exit from the cell cycle. Fibroblast growth factor-2 (FGF-2) has been reported to play multiple roles in different biological processes during development of the central nervous system (CNS). In addition, FGF-2 has been described to induce \"neuronal-like\" differentiation and trigger apoptosis in neuroblastoma SK-N-MC cells. Although regulation of Id-1 protein by several mitogenic factors is well-established, little is known about the role of FGF-2 in the regulation of Id-1. Using human neuroblastoma cell line, SK-N-MC, we found that treatment of these cells with FGF-2 resulted in early induction of both Id-1 mRNA and protein. The induction occurs within 1 h from FGF-2 treatment and is mediated by ERK1/2 pathway, which in turn stimulates expression of the early growth response-1 (Egr-1) transcription factor. We also demonstrate direct interaction of Egr-1 with Id-1 promoter in vitro and in cell culture. Finally, inhibition of Id-1 expression results in G(2) /M accumulation of FGF-2-treated cells and delayed cell death.\n" ], "offsets": [ [ 0, 1645 ] ] } ]

[ { "id": "PMID-21506108_T4", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 69, 88 ] ], "normalized": [] }, { "id": "PMID-21506108_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 92, 96 ] ], "normalized": [] }, { "id": "PMID-21506108_T9", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 383, 387 ] ], "normalized": [] }, { "id": "PMID-21506108_T10", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 422, 426 ] ], "normalized": [] }, { "id": "PMID-21506108_T12", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 512, 516 ] ], "normalized": [] }, { "id": "PMID-21506108_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 560, 564 ] ], "normalized": [] }, { "id": "PMID-21506108_T14", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "PMID-21506108_T17", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 773, 795 ] ], "normalized": [] }, { "id": "PMID-21506108_T18", "type": "Anatomical_system", "text": [ "CNS" ], "offsets": [ [ 797, 800 ] ], "normalized": [] }, { "id": "PMID-21506108_T20", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "PMID-21506108_T21", "type": "Cell", "text": [ "neuroblastoma SK-N-MC cells" ], "offsets": [ [ 908, 935 ] ], "normalized": [] }, { "id": "PMID-21506108_T26", "type": "Cell", "text": [ "neuroblastoma cell line" ], "offsets": [ [ 1102, 1125 ] ], "normalized": [] }, { "id": "PMID-21506108_T27", "type": "Cell", "text": [ "SK-N-MC" ], "offsets": [ [ 1127, 1134 ] ], "normalized": [] }, { "id": "PMID-21506108_T28", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "PMID-21506108_T37", "type": "Cell", "text": [ "cell culture" ], "offsets": [ [ 1513, 1525 ] ], "normalized": [] }, { "id": "PMID-21506108_T40", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1615, 1620 ] ], "normalized": [] }, { "id": "PMID-21506108_T41", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1633, 1637 ] ], "normalized": [] } ]

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[ { "id": "PMID-10978248__text", "type": "abstract", "text": [ "Vasodilator-stimulated phosphoprotein is involved in stress-fiber and membrane ruffle formation in endothelial cells.\nVasodilator-stimulated phosphoprotein (VASP) is highly expressed in vascular endothelial cells, where it has been implicated in cellular reorganization during angiogenesis, as well as in endothelial retraction and changes in vessel permeability. However, the cellular functions of VASP are not known. In this study, we have expressed wild-type and mutant forms of VASP in endothelial cells to determine in what aspects of cytoskeletal behavior this protein participates. Expression of wild-type VASP induces marked membrane ruffling and formation of prominent stress fibers in bovine aortic endothelial cells. Deletion of the proline-rich domain of VASP abolishes its ability to bind profilin but does not affect ruffling or stress fiber formation. Further deletions reveal a sequence within the carboxy-terminal domain that is responsible for in vivo bundle formation. Ruffling occurs only on the expression of forms of VASP that possess bundling activity and the capacity to bind zyxin/vinculin-derived peptide. The ability of distinct subdomains within VASP to bind adhesion proteins and induce F-actin bundling in vivo suggests that this protein could function in the aggregation and tethering of actin filaments during the formation of endothelial cell-substrate and cell-cell contacts. These data provide a mechanism whereby VASP can influence endothelial migration and organization during capillary formation and modulate vascular permeability via effects on endothelial cell contractility.\n" ], "offsets": [ [ 0, 1616 ] ] } ]

[ { "id": "PMID-10978248_T2", "type": "Cellular_component", "text": [ "stress-fiber" ], "offsets": [ [ 53, 65 ] ], "normalized": [] }, { "id": "PMID-10978248_T3", "type": "Cellular_component", "text": [ "membrane ruffle" ], "offsets": [ [ 70, 85 ] ], "normalized": [] }, { "id": "PMID-10978248_T4", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 99, 116 ] ], "normalized": [] }, { "id": "PMID-10978248_T7", "type": "Cell", "text": [ "vascular endothelial cells" ], "offsets": [ [ 186, 212 ] ], "normalized": [] }, { "id": "PMID-10978248_T8", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 246, 254 ] ], "normalized": [] }, { "id": "PMID-10978248_T9", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 305, 316 ] ], "normalized": [] }, { "id": "PMID-10978248_T10", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 343, 349 ] ], "normalized": [] }, { "id": "PMID-10978248_T11", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 377, 385 ] ], "normalized": [] }, { "id": "PMID-10978248_T14", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 490, 507 ] ], "normalized": [] }, { "id": "PMID-10978248_T15", "type": "Cellular_component", "text": [ "cytoskeletal" ], "offsets": [ [ 540, 552 ] ], "normalized": [] }, { "id": "PMID-10978248_T17", "type": "Cellular_component", "text": [ "membrane" ], "offsets": [ [ 633, 641 ] ], "normalized": [] }, { "id": "PMID-10978248_T18", "type": "Cellular_component", "text": [ "stress fibers" ], "offsets": [ [ 678, 691 ] ], "normalized": [] }, { "id": "PMID-10978248_T20", "type": "Cell", "text": [ "aortic endothelial cells" ], "offsets": [ [ 702, 726 ] ], "normalized": [] }, { "id": "PMID-10978248_T23", "type": "Cellular_component", "text": [ "stress fiber" ], "offsets": [ [ 843, 855 ] ], "normalized": [] }, { "id": "PMID-10978248_T30", "type": "Cellular_component", "text": [ "endothelial cell-substrate" ], "offsets": [ [ 1359, 1385 ] ], "normalized": [] }, { "id": "PMID-10978248_T31", "type": "Cellular_component", "text": [ "cell-cell contacts" ], "offsets": [ [ 1390, 1408 ] ], "normalized": [] }, { "id": "PMID-10978248_T33", "type": "Cell", "text": [ "endothelial" ], "offsets": [ [ 1468, 1479 ] ], "normalized": [] }, { "id": "PMID-10978248_T34", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1514, 1523 ] ], "normalized": [] }, { "id": "PMID-10978248_T35", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 1547, 1555 ] ], "normalized": [] }, { "id": "PMID-10978248_T36", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 1584, 1600 ] ], "normalized": [] }, { "id": "PMID-10978248_T68", "type": "Cellular_component", "text": [ "actin filaments" ], "offsets": [ [ 1319, 1334 ] ], "normalized": [] }, { "id": "PMID-10978248_T1", "type": "Cellular_component", "text": [ "bundle" ], "offsets": [ [ 970, 976 ] ], "normalized": [] } ]

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[ { "id": "PMID-9843597__text", "type": "abstract", "text": [ "Glucagon induces suppression of ATP-sensitive K+ channel activity through a Ca2+/calmodulin-dependent pathway in mouse pancreatic beta-cells.\nGlucagon is known to increase intracellular cAMP levels and enhance glucose-induced electrical activity and insulin secretion in pancreatic beta-cell perfused with Krebs-Ringer bicarbonate solution. The present experiments were aimed at evaluation of the hypothesis that changes in beta-cells ATP-sensitive K+ (K(ATP)) channel activity are involved in the glucagon-induced enhancement of electrical activity. Channel activity was recorded using the cell-attached configuration of the patch-clamp technique. Addition of glucagon (2.9 x 10(-7) m) in the presence of 11.1 mm glucose caused closure of K(ATP) channels followed by an increase in the frequency of biphasic current transients (action currents) due to action potential generation in the cell. Three calmodulin-antagonists (W-7, chlorpromazine, and trifluoperazine) restored with similar efficacy K(ATP) channel activity in cells being exposed to glucagon. At 2.8 mm glucose, glucagon did not affect K(ATP) channel activity until Ca2+ was released from Nitr-5 by flash photolysis, at which point channel activity was transiently suppressed. Similar effects were seen when db-cAMP was used instead of glucagon. These results support the view that glucagon and other cAMP-generating agonists enhance glucose-induced beta-cell electrical activity through a Ca2+/calmodulin dependent-closure of K(ATP) channels.\n" ], "offsets": [ [ 0, 1508 ] ] } ]

[ { "id": "PMID-9843597_T1", "type": "Cell", "text": [ "pancreatic beta-cells" ], "offsets": [ [ 119, 140 ] ], "normalized": [] }, { "id": "PMID-9843597_T2", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 172, 185 ] ], "normalized": [] }, { "id": "PMID-9843597_T3", "type": "Cell", "text": [ "pancreatic beta-cell" ], "offsets": [ [ 271, 291 ] ], "normalized": [] }, { "id": "PMID-9843597_T4", "type": "Cell", "text": [ "beta-cells" ], "offsets": [ [ 424, 434 ] ], "normalized": [] }, { "id": "PMID-9843597_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 591, 595 ] ], "normalized": [] }, { "id": "PMID-9843597_T6", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 888, 892 ] ], "normalized": [] }, { "id": "PMID-9843597_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1024, 1029 ] ], "normalized": [] }, { "id": "PMID-9843597_T8", "type": "Cell", "text": [ "beta-cell" ], "offsets": [ [ 1414, 1423 ] ], "normalized": [] } ]

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[ { "id": "PMC-1971061-sec-09__text", "type": "sec", "text": [ "Etiology\nAnorectal malformations (ARM) represent a spectrum of abnormalities ranging from mild anal anomalies to complex cloacal malformations. The etiology of such malformations remains unclear and is likely multifactorial. There are however reasons to believe there is a genetic componenet. As early as the 1950s, it was recognized that there was an increased risk for a sibling of a patient with ARM to be born with a malformation, as much as 1 in 100, compared with the incidence of about 1 in 5000 in the general population. Since that time there have been reports of families with 2 or more affected members and associations of ARMs with multisystem syndromes. In particular, mutations in specific genes encoding transcription factors have been described in patients having Townes-Broks syndrome, Currarino's syndrome, and Pallister-Hall syndrome, each of which have autosomal dominant modes of inheritance. In addition, it has been found that there is not only an increased incidence of ARM in patient with trisomy 21 (Down's syndrome), but that 95% of patients with trisomy 21 and ARM have imperforate anus without fistula, compared with only 5% of all patients with ARM. Based on this evidence, it is likely that the mutation of a variety of different genes can result in ARM, or that the etiology of ARM is multigenic [13].\n" ], "offsets": [ [ 0, 1334 ] ] } ]

[ { "id": "PMC-1971061-sec-09_T1", "type": "Organism_subdivision", "text": [ "Anorectal" ], "offsets": [ [ 9, 18 ] ], "normalized": [] }, { "id": "PMC-1971061-sec-09_T2", "type": "Immaterial_anatomical_entity", "text": [ "anal" ], "offsets": [ [ 95, 99 ] ], "normalized": [] }, { "id": "PMC-1971061-sec-09_T3", "type": "Immaterial_anatomical_entity", "text": [ "anus" ], "offsets": [ [ 1110, 1114 ] ], "normalized": [] }, { "id": "PMC-1971061-sec-09_T4", "type": "Pathological_formation", "text": [ "fistula" ], "offsets": [ [ 1123, 1130 ] ], "normalized": [] } ]

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[ { "id": "PMID-11909360__text", "type": "abstract", "text": [ "Novel method for multiturn extraction: trapping charged particles in islands of phase space.\nA novel method for multiturn extraction from a circular particle accelerator is presented, based on trapping particles into islands of phase space generated by nonlinear resonances. By appropriate use of sextupoles and octupoles, stable islands can be created at small amplitude in phase space. By varying the linear tune, particles can be trapped inside these islands and then transported towards higher amplitudes for extraction. Results of numerical simulations are discussed.\n" ], "offsets": [ [ 0, 573 ] ] } ]

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[ { "id": "PMC-2217075-caption-07__text", "type": "caption", "text": [ "Anion to cation selectivity ratio determined from the relative rates of reaction of MTSES- and MTSET+ with the water exposed residues in the M6 segment. The anion selectivity ratio is calculated as described in Table II, column 5. Note the marked increase in anion selectivity at the residues T351C and Q353C. A ratio of 1 indicates no selectivity between anions and cations. The larger the ratio the greater the anion selectivity.\n" ], "offsets": [ [ 0, 432 ] ] } ]

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[ { "id": "PMID-9394578__text", "type": "abstract", "text": [ "[Extra-anatomic bypass from the ascending aorta to the supraceliac abdominal aorta--surgical option applied to reoperation for aortic coarctation or interruption].\nThe optimal approach for reoperation following repair of aortic coarctation (CoA) or interruption (IAA) remains controversial. Four patients underwent extra-anatomic bypass for restenosis after repair of CoA or IAA. The age ranged from 4 to 12 years. The initial repairs for two CoA, one type A-IAA, and one type B-IAA consisted of two grafting, one subclavian arterial turning-down aortoplasty, and one subclavian flap aortoplasty. All of them underwent during infancy. Preoperative right arm systolic pressure ranged from 140 to 190 mmHg ar rest. Through a midline sternotomy and an upper laparotmy incision, an extra-anatomic bypass from the ascending aorta to the supraceliac abdominal aorta was employed using a 12 to 18 mm tube graft. All patients survived surgeries, and their hypertension markedly improved. Our experience confirms safety and effectiveness of this option in selected young patients with re-stenosis of following repair of CoA or IAA.\n" ], "offsets": [ [ 0, 1123 ] ] } ]

[ { "id": "PMID-9394578_T1", "type": "Multi-tissue_structure", "text": [ "abdominal aorta" ], "offsets": [ [ 67, 82 ] ], "normalized": [] }, { "id": "PMID-9394578_T2", "type": "Multi-tissue_structure", "text": [ "aortic" ], "offsets": [ [ 221, 227 ] ], "normalized": [] }, { "id": "PMID-9394578_T3", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "PMID-9394578_T4", "type": "Organism_subdivision", "text": [ "right arm" ], "offsets": [ [ 648, 657 ] ], "normalized": [] }, { "id": "PMID-9394578_T5", "type": "Multi-tissue_structure", "text": [ "abdominal aorta" ], "offsets": [ [ 844, 859 ] ], "normalized": [] }, { "id": "PMID-9394578_T7", "type": "Multi-tissue_structure", "text": [ "aortic" ], "offsets": [ [ 127, 133 ] ], "normalized": [] }, { "id": "PMID-9394578_T8", "type": "Multi-tissue_structure", "text": [ "flap" ], "offsets": [ [ 579, 583 ] ], "normalized": [] }, { "id": "PMID-9394578_T9", "type": "Multi-tissue_structure", "text": [ "ascending aorta" ], "offsets": [ [ 809, 824 ] ], "normalized": [] }, { "id": "PMID-9394578_T10", "type": "Multi-tissue_structure", "text": [ "ascending aorta" ], "offsets": [ [ 32, 47 ] ], "normalized": [] } ]

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[ { "id": "PMID-15623651__text", "type": "abstract", "text": [ "2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma.\nPURPOSE: Head and neck squamous cell carcinomas have been reported to overexpress hypoxia-inducible factor (HIF)-1alpha, a transcription factor that promotes expression of angiogenesis factors and resistance to programmed and therapy-induced cell death. 2-Methoxyestradiol (2ME2) is a natural compound with HIF-1alpha inhibitory activity that is currently being evaluated in phase 1 and 2 clinical trials for advanced solid tumors and multiple myeloma. To our knowledge, this is the first study to evaluate the effects of 2ME2 in head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: In the present study, we investigated the effects of 2ME2 alone and in combination with paclitaxel, an active agent in recurrent or advanced head and neck squamous cell carcinoma. RESULTS: 2ME2 exhibited antiproliferative and cytotoxic effects in a panel of five head and neck squamous cell carcinoma cell lines in the 0.5 to 10 micromol/L range, including induction of G2-M blockade, caspase-3/7 activation, and apoptosis at 48 hours. 2ME2 resulted in decreased nuclear HIF-1alpha-binding activity and affected the expression of downstream genes, such as bid, a proapoptotic bcl-2 family member, and vascular endothelial growth factor, a proangiogenic cytokine. The up-regulation of Bid (57.5% at 12 hours, P less than 0.0006) and inhibition of vascular endothelial growth factor secretion (57.7% at 24 hours, P less than 0.015; and 50.3% at 48 hours, P less than 0.0006) could be partially attributed to the effects on HIF-1alpha, because HIF-1alpha small interfering RNAs produced similar effects. Finally, in vivo, in a xenograft model of head and neck squamous cell carcinoma using UM-SCC-11A cells, 2ME2 exhibited antitumor and antiangiogenic activity, as measured by CD31 immunostaining. CONCLUSIONS: These results provide support for the use of 2ME2 in combination with paclitaxel for the treatment of recurrent or advanced head and neck squamous cell carcinoma.\n" ], "offsets": [ [ 0, 2134 ] ] } ]

[ { "id": "PMID-15623651_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 61, 66 ] ], "normalized": [] }, { "id": "PMID-15623651_T5", "type": "Cancer", "text": [ "head and neck squamous cell carcinoma" ], "offsets": [ [ 128, 165 ] ], "normalized": [] }, { "id": "PMID-15623651_T6", "type": "Cancer", "text": [ "Head and neck squamous cell carcinomas" ], "offsets": [ [ 176, 214 ] ], "normalized": [] }, { "id": "PMID-15623651_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-15623651_T12", "type": "Cancer", "text": [ "solid tumors" ], "offsets": [ [ 585, 597 ] ], "normalized": [] }, { "id": "PMID-15623651_T13", "type": "Cancer", "text": [ "myeloma" ], "offsets": [ [ 611, 618 ] ], "normalized": [] }, { "id": "PMID-15623651_T15", "type": "Cancer", "text": [ "head and neck squamous cell carcinoma" ], "offsets": [ [ 697, 734 ] ], "normalized": [] }, { "id": "PMID-15623651_T18", "type": "Cancer", "text": [ "head and neck squamous cell carcinoma" ], "offsets": [ [ 898, 935 ] ], "normalized": [] }, { "id": "PMID-15623651_T20", "type": "Cell", "text": [ "head and neck squamous cell carcinoma cell lines" ], "offsets": [ [ 1020, 1068 ] ], "normalized": [] }, { "id": "PMID-15623651_T32", "type": "Cancer", "text": [ "xenograft" ], "offsets": [ [ 1787, 1796 ] ], "normalized": [] }, { "id": "PMID-15623651_T33", "type": "Cancer", "text": [ "head and neck squamous cell carcinoma" ], "offsets": [ [ 1806, 1843 ] ], "normalized": [] }, { "id": "PMID-15623651_T34", "type": "Cell", "text": [ "UM-SCC-11A cells" ], "offsets": [ [ 1850, 1866 ] ], "normalized": [] }, { "id": "PMID-15623651_T36", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1887, 1892 ] ], "normalized": [] }, { "id": "PMID-15623651_T40", "type": "Cancer", "text": [ "head and neck squamous cell carcinoma" ], "offsets": [ [ 2095, 2132 ] ], "normalized": [] }, { "id": "PMID-15623651_T71", "type": "Cellular_component", "text": [ "nuclear" ], "offsets": [ [ 1220, 1227 ] ], "normalized": [] } ]

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[ { "id": "PMID-1683740__text", "type": "abstract", "text": [ "Changes of lymphocyte subsets in leukemia patients who received allogenic bone marrow transplantation.\nProportional changes of lymphocyte subsets in the peripheral blood were monitored by two-color flow-cytometry in seven leukemia patients who had received allogenic bone marrow transplantation (BMT). Lymphocyte counts, and proportions of T and B-cells returned to normal ranges between the 2nd and 12th months after BMT. Activated T-cells prominently increased after BMT, and the values gradually returned toward normal. As to lymphocyte subsets, the proportions of CD 4+ cells had remained low, while those of CD 8+ cells high for a whole observation period after BMT. The changes of CD 4+ cells were caused by the decrease of suppressor-inducer T-cells (CD 4+ Leu 8+). High proportion of CD 8+ cells was mainly associated with increased suppressor T-cells (CD 8+ CD 11+). Among natural killer (NK) cells, highly active NK cells (CD 16+ CD 57-) markedly increased shortly after BMT, and gradually returned to normal. CD 16 -CD 57+ NK cells increased beyond normal ranges after the 2nd month. The incidence or degree of acute and chronic graft-versus-host diseases (GVHD) did not correlate with the changes of any lymphocyte subsets. The present results suggest that the increase of activated T-cells shortly after BMT reflects lymphocyte reconstitution. The prolonged immune deficiency after BMT might be related to either deficient expression of homing receptor (Leu 8 antigen) on CD 4+ cells or increased suppressor T-cells (CD 8+ CD 11+). In addition, the early increase of NK cells after BMT may compensate for the immune deficiency in BMT patients.\n" ], "offsets": [ [ 0, 1657 ] ] } ]

[ { "id": "PMID-1683740_T1", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 11, 21 ] ], "normalized": [] }, { "id": "PMID-1683740_T2", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 74, 85 ] ], "normalized": [] }, { "id": "PMID-1683740_T3", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 127, 137 ] ], "normalized": [] }, { "id": "PMID-1683740_T4", "type": "Organism_substance", "text": [ "peripheral blood" ], "offsets": [ [ 153, 169 ] ], "normalized": [] }, { "id": "PMID-1683740_T5", "type": "Multi-tissue_structure", "text": [ "bone marrow" ], "offsets": [ [ 267, 278 ] ], "normalized": [] }, { "id": "PMID-1683740_T6", "type": "Cell", "text": [ "Lymphocyte" ], "offsets": [ [ 302, 312 ] ], "normalized": [] }, { "id": "PMID-1683740_T7", "type": "Cell", "text": [ "T" ], "offsets": [ [ 340, 341 ] ], "normalized": [] }, { "id": "PMID-1683740_T8", "type": "Cell", "text": [ "B-cells" ], "offsets": [ [ 346, 353 ] ], "normalized": [] }, { "id": "PMID-1683740_T9", "type": "Cell", "text": [ "T-cells" ], "offsets": [ [ 433, 440 ] ], "normalized": [] }, { "id": "PMID-1683740_T10", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 529, 539 ] ], "normalized": [] }, { "id": "PMID-1683740_T11", "type": "Cell", "text": [ "CD 4+ cells" ], "offsets": [ [ 568, 579 ] ], "normalized": [] }, { "id": "PMID-1683740_T12", "type": "Cell", "text": [ "CD 8+ cells" ], "offsets": [ [ 613, 624 ] ], "normalized": [] }, { "id": "PMID-1683740_T13", "type": "Cell", "text": [ "CD 4+ cells" ], "offsets": [ [ 687, 698 ] ], "normalized": [] }, { "id": "PMID-1683740_T14", "type": "Cell", "text": [ "suppressor-inducer T-cells" ], "offsets": [ [ 730, 756 ] ], "normalized": [] }, { "id": "PMID-1683740_T15", "type": "Cell", "text": [ "CD 8+ cells" ], "offsets": [ [ 792, 803 ] ], "normalized": [] }, { "id": "PMID-1683740_T16", "type": "Cell", "text": [ "suppressor T-cells" ], "offsets": [ [ 841, 859 ] ], "normalized": [] }, { "id": "PMID-1683740_T17", "type": "Cell", "text": [ "natural killer (NK) cells" ], "offsets": [ [ 882, 907 ] ], "normalized": [] }, { "id": "PMID-1683740_T18", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 923, 931 ] ], "normalized": [] }, { "id": "PMID-1683740_T19", "type": "Cell", "text": [ "CD 16 -CD 57+ NK cells" ], "offsets": [ [ 1020, 1042 ] ], "normalized": [] }, { "id": "PMID-1683740_T20", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 1216, 1226 ] ], "normalized": [] }, { "id": "PMID-1683740_T21", "type": "Cell", "text": [ "T-cells" ], "offsets": [ [ 1295, 1302 ] ], "normalized": [] }, { "id": "PMID-1683740_T22", "type": "Cell", "text": [ "lymphocyte" ], "offsets": [ [ 1330, 1340 ] ], "normalized": [] }, { "id": "PMID-1683740_T23", "type": "Cell", "text": [ "CD 4+ cells" ], "offsets": [ [ 1485, 1496 ] ], "normalized": [] }, { "id": "PMID-1683740_T24", "type": "Cell", "text": [ "suppressor T-cells" ], "offsets": [ [ 1510, 1528 ] ], "normalized": [] }, { "id": "PMID-1683740_T25", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 1580, 1588 ] ], "normalized": [] }, { "id": "PMID-1683740_T26", "type": "Multi-tissue_structure", "text": [ "graft" ], "offsets": [ [ 1140, 1145 ] ], "normalized": [] }, { "id": "PMID-1683740_T31", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 33, 41 ] ], "normalized": [] }, { "id": "PMID-1683740_T32", "type": "Cancer", "text": [ "leukemia" ], "offsets": [ [ 222, 230 ] ], "normalized": [] } ]

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[ { "id": "PMID-3609047__text", "type": "abstract", "text": [ "Torsade de pointes during loading with amiodarone.\nTorsade de pointes represents a potential complication of chronic amiodarone therapy. Several reports have emphasized the need for a loading dose in order to achieve therapeutic blood levels rapidly. We report a case of torsade de pointes following a single oral dose of amiodarone (1400 mg or 30 mg kg-1) administered after short intravenous loading for prevention of paroxysmal atrial flutter. Torsades de pointes were preceded and associated with marked QT prolongation and bradycardia. This report suggests that careful monitoring of patients undergoing oral amiodarone loading is necessary.\n" ], "offsets": [ [ 0, 647 ] ] } ]

[ { "id": "PMID-3609047_T1", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 229, 234 ] ], "normalized": [] }, { "id": "PMID-3609047_T2", "type": "Immaterial_anatomical_entity", "text": [ "intravenous" ], "offsets": [ [ 382, 393 ] ], "normalized": [] }, { "id": "PMID-3609047_T3", "type": "Immaterial_anatomical_entity", "text": [ "atrial" ], "offsets": [ [ 431, 437 ] ], "normalized": [] }, { "id": "PMID-3609047_T4", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 309, 313 ] ], "normalized": [] }, { "id": "PMID-3609047_T5", "type": "Organism_subdivision", "text": [ "oral" ], "offsets": [ [ 609, 613 ] ], "normalized": [] } ]

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[ { "id": "PMID-19292679__text", "type": "abstract", "text": [ "The effect of perfluorocarbon-based artificial oxygen carriers on tissue-engineered trachea.\nThe biological effect of the perfluorocarbon-based artificial oxygen carrier (Oxygent) was investigated in tissue-engineered trachea (TET) construction. Media supplemented with and without 10% Oxygent were compared in all assessments. Partial tissue oxygen tension (PtO(2)) was measured with polarographic microprobes; epithelial metabolism was monitored by microdialysis inside the TET epithelium perfused with the medium underneath. Chondrocyte-DegraPol constructs were cultured for 1 month with the medium before glycosaminoglycan assessment and histology. Tissue reaction of TET epithelial scaffolds immersed with the medium was evaluated on the chick embryo chorioallantoic membrane. Oxygent perfusion medium increased the TET epithelial PtO(2) (51.2 +/- 0.3 mm Hg vs. 33.4 +/- 0.3 mm Hg at 200 microm thickness; 12.5 +/- 0.1 mm Hg vs. 3.1 +/- 0.1 mm Hg at 400 microm thickness, p less than 0.01) and decreased the lactate concentration (0.63 +/- 0.08 vs. 0.80 +/- 0.06 mmol/L, p less than 0.05), lactate/pyruvate (1.87 +/- 0.26 vs. 3.36 +/- 10.13, p less than 0.05), and lactate/glucose ratios (0.10 +/- 0.00 vs. 0.29 +/- 0.14, p less than 0.05). Chondrocyte-DegraPol in Oxygent group presented lower glycosaminoglycan value (0.03 +/- 0.00 vs. 0.13 +/- 0.00, p less than 0.05); histology slides showed poor acid mucopolysaccharides formation. Orthogonal polarization spectral imaging showed no difference in functional capillary density between the scaffolds cultured on chorioallantoic membranes. The foreign body reaction was similar in both groups. We conclude that Oxygent increases TET epithelial PtO(2), improves epithelial metabolism, does not impair angiogenesis, and tends to slow cartilage tissue formation.\n" ], "offsets": [ [ 0, 1827 ] ] } ]

[ { "id": "PMID-19292679_T3", "type": "Multi-tissue_structure", "text": [ "tissue-engineered trachea" ], "offsets": [ [ 66, 91 ] ], "normalized": [] }, { "id": "PMID-19292679_T7", "type": "Multi-tissue_structure", "text": [ "tissue-engineered trachea" ], "offsets": [ [ 200, 225 ] ], "normalized": [] }, { "id": "PMID-19292679_T8", "type": "Multi-tissue_structure", "text": [ "TET" ], "offsets": [ [ 227, 230 ] ], "normalized": [] }, { "id": "PMID-19292679_T10", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 336, 342 ] ], "normalized": [] }, { "id": "PMID-19292679_T12", "type": "Cell", "text": [ "epithelial" ], "offsets": [ [ 412, 422 ] ], "normalized": [] }, { "id": "PMID-19292679_T13", "type": "Tissue", "text": [ "TET epithelium" ], "offsets": [ [ 476, 490 ] ], "normalized": [] }, { "id": "PMID-19292679_T14", "type": "Cell", "text": [ "Chondrocyte" ], "offsets": [ [ 528, 539 ] ], "normalized": [] }, { "id": "PMID-19292679_T16", "type": "Tissue", "text": [ "Tissue" ], "offsets": [ [ 653, 659 ] ], "normalized": [] }, { "id": "PMID-19292679_T17", "type": "Tissue", "text": [ "TET epithelial scaffolds" ], "offsets": [ [ 672, 696 ] ], "normalized": [] }, { "id": "PMID-19292679_T19", "type": "Multi-tissue_structure", "text": [ "embryo chorioallantoic membrane" ], "offsets": [ [ 749, 780 ] ], "normalized": [] }, { "id": "PMID-19292679_T21", "type": "Tissue", "text": [ "TET epithelial" ], "offsets": [ [ 821, 835 ] ], "normalized": [] }, { "id": "PMID-19292679_T27", "type": "Cell", "text": [ "Chondrocyte" ], "offsets": [ [ 1254, 1265 ] ], "normalized": [] }, { "id": "PMID-19292679_T31", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1528, 1537 ] ], "normalized": [] }, { "id": "PMID-19292679_T32", "type": "Multi-tissue_structure", "text": [ "chorioallantoic membranes" ], "offsets": [ [ 1580, 1605 ] ], "normalized": [] }, { "id": "PMID-19292679_T34", "type": "Tissue", "text": [ "TET epithelial" ], "offsets": [ [ 1696, 1710 ] ], "normalized": [] }, { "id": "PMID-19292679_T35", "type": "Tissue", "text": [ "epithelial" ], "offsets": [ [ 1728, 1738 ] ], "normalized": [] }, { "id": "PMID-19292679_T36", "type": "Tissue", "text": [ "cartilage tissue" ], "offsets": [ [ 1799, 1815 ] ], "normalized": [] }, { "id": "PMID-19292679_T46", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 1619, 1623 ] ], "normalized": [] } ]

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[ { "id": "PMID-19679742__text", "type": "abstract", "text": [ "Aging affects the cardiovascular responses to cold stress in humans.\nCardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 +/- 1 (SE) yr old] and 12 older (65 +/- 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults (P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining approximately 63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness.\n" ], "offsets": [ [ 0, 1558 ] ] } ]

[ { "id": "PMID-19679742_T1", "type": "Anatomical_system", "text": [ "cardiovascular" ], "offsets": [ [ 18, 32 ] ], "normalized": [] }, { "id": "PMID-19679742_T2", "type": "Anatomical_system", "text": [ "Cardiovascular" ], "offsets": [ [ 69, 83 ] ], "normalized": [] }, { "id": "PMID-19679742_T3", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 217, 222 ] ], "normalized": [] }, { "id": "PMID-19679742_T4", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 325, 330 ] ], "normalized": [] }, { "id": "PMID-19679742_T5", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 510, 514 ] ], "normalized": [] }, { "id": "PMID-19679742_T6", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 651, 655 ] ], "normalized": [] }, { "id": "PMID-19679742_T7", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 688, 693 ] ], "normalized": [] }, { "id": "PMID-19679742_T8", "type": "Organism_subdivision", "text": [ "brachial" ], "offsets": [ [ 1005, 1013 ] ], "normalized": [] }, { "id": "PMID-19679742_T9", "type": "Multi-tissue_structure", "text": [ "aorta" ], "offsets": [ [ 1045, 1050 ] ], "normalized": [] }, { "id": "PMID-19679742_T10", "type": "Multi-tissue_structure", "text": [ "aortic" ], "offsets": [ [ 1105, 1111 ] ], "normalized": [] }, { "id": "PMID-19679742_T11", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 1154, 1162 ] ], "normalized": [] }, { "id": "PMID-19679742_T12", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1270, 1274 ] ], "normalized": [] }, { "id": "PMID-19679742_T13", "type": "Multi-tissue_structure", "text": [ "arterial" ], "offsets": [ [ 1538, 1546 ] ], "normalized": [] }, { "id": "PMID-19679742_T14", "type": "Organism_substance", "text": [ "blood" ], "offsets": [ [ 848, 853 ] ], "normalized": [] }, { "id": "PMID-19679742_T15", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 390, 394 ] ], "normalized": [] }, { "id": "PMID-19679742_T16", "type": "Organism_subdivision", "text": [ "body" ], "offsets": [ [ 1429, 1433 ] ], "normalized": [] }, { "id": "PMID-19679742_T17", "type": "Multi-tissue_structure", "text": [ "sites" ], "offsets": [ [ 1064, 1069 ] ], "normalized": [] } ]

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[ { "id": "PMID-16850045__text", "type": "abstract", "text": [ "Fluoroscopically guided cervical prolotherapy for instability with blinded pre and post radiographic reading.\nBACKGROUND:\nSeveral authors have postulated that cervical instability is a major cause of traumatic spinal pain.\nOBJECTIVE:\nThe purpose of this prospective case series study (n = 6) was to determine if proliferant injections have an effect on cervical translation as measured by a blinded reader.\nDESIGN:\nThis study was a prospective case series. Study participants were selected from patients seen for the primary complaint of Motor Vehicle Collision related neck pain in a private sub-specialty pain clinic.\nMETHODS:\nFlexion and extension views were obtained by standard radiographs taken with a C-Arm fluoroscope under Valium sedation. Patients with more than 2.7 mm of absolute cervical translation and at least 50% reduction of cervical and referred pain with a two day rigid cervical immobilization test were admitted into the study. Participants underwent 3 prolotherapy injections at all sites that demonstrated translation. The difference in means between pre-test and post-test measurements (flexion translation, extension translation, and pain VAS scores) were assessed by a Wilcoxon signed ranks test (alpha = 0.05).\nRESULTS:\nThe mean post-test VAS score (M= 3.83, SD=2.3, t=2.889) was significantly less (p=0.04) than the mean pre-test VAS score (M=5.75, SD=1.94). The correlation between difference in mean extension at C2-3 and C5-6 and difference in mean extension was significant (rho=0.89, p=0.02 and rho=0.85, p=0.03 respectively). Difference in mean flexion at C3-4 and C4-5 was significantly correlated with difference in mean flexion (rho=0.88, p=0.02 and rho=0.941, p <0.01 respectively).\nCONCLUSIONS:\nThe results of this study demonstrate statistically significant correlations between proliferant injections, a reduction of both cervical flexion and extension translation, as well as a reduction in pain VAS score. Since patients with traumatic cervical instability have few viable treatment options other than surgical fusion, cervical proliferant injections under C-Arm fluoroscope may be a viable treatment option.\n" ], "offsets": [ [ 0, 2153 ] ] } ]

[ { "id": "PMID-16850045_T1", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 24, 32 ] ], "normalized": [] }, { "id": "PMID-16850045_T2", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 159, 167 ] ], "normalized": [] }, { "id": "PMID-16850045_T3", "type": "Organism_subdivision", "text": [ "spinal" ], "offsets": [ [ 210, 216 ] ], "normalized": [] }, { "id": "PMID-16850045_T4", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 353, 361 ] ], "normalized": [] }, { "id": "PMID-16850045_T5", "type": "Organism_subdivision", "text": [ "neck" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-16850045_T6", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 792, 800 ] ], "normalized": [] }, { "id": "PMID-16850045_T7", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 843, 851 ] ], "normalized": [] }, { "id": "PMID-16850045_T8", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 891, 899 ] ], "normalized": [] }, { "id": "PMID-16850045_T9", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 1864, 1872 ] ], "normalized": [] }, { "id": "PMID-16850045_T10", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 1980, 1988 ] ], "normalized": [] }, { "id": "PMID-16850045_T11", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 2063, 2071 ] ], "normalized": [] } ]

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[ { "id": "PMID-1553573__text", "type": "abstract", "text": [ "Granulocyte-macrophage colony-stimulating factor and interleukin-3 enhance the incorporation of cytosine arabinoside into the DNA of leukemic blasts and the cytotoxic effect on clonogenic cells from patients with acute myeloid leukemia. \nIn the present study the effects of the 48-hour administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) (100 U/mL) or interleukin-3 (IL-3) (100 U/mL) on the proliferative activity of leukemic cells and on the intracellular metabolism and cytotoxic efficacy of a subsequent 12-hour application of cytosine arabinoside (ara-C) at doses of 0.1, 1.0, 10.0, and 100.0 mumol/L were evaluated on bone marrow cells from 17 patients with acute myeloid leukemia. After GM-CSF or IL-3, a 1.2- to 2.4-fold increase in S-phase cells was observed in nine of 14 GM-CSF and seven of 11 IL-3 cases. 3H-Cytosine arabinoside incorporation into the DNA was enhanced 1.33- to 18.3-fold over respective controls in 14 of 17 patients. While in control specimens are ara-C dose-dependent increase in 3H-ara-C uptake was accompanied by a corresponding rise in intracellular ara-C-5' triphosphate (ara-CTP) levels, ara-CTP concentrations were not increased after GM-CSF or IL-3 exposure, resulting in a higher ara-C to ara-CTP ratio over controls. This finding may be explained by a stimulatory effect of GM-CSF and IL-3 on ara-C phosphorylating enzymes and a more rapid incorporation of ara-CTP into the DNA of leukemic blasts. These effects translated into a 2.2- to 229.0-fold increase in the cytotoxic activity of ara-C against clonogenic leukemic cells after GM-CSF or IL-3 pretreatment. Hence, GM-CSF and IL-3 enhance the intracellular metabolism of ara-C and its incorporation into the DNA of leukemic cells leading to a higher antileukemic activity of ara-C on clonogenic leukemic cells (CFU-L).\n" ], "offsets": [ [ 0, 1836 ] ] } ]

[ { "id": "PMID-1553573_T5", "type": "Cell", "text": [ "leukemic blasts" ], "offsets": [ [ 133, 148 ] ], "normalized": [] }, { "id": "PMID-1553573_T6", "type": "Cell", "text": [ "clonogenic cells" ], "offsets": [ [ 177, 193 ] ], "normalized": [] }, { "id": "PMID-1553573_T8", "type": "Cancer", "text": [ "acute myeloid leukemia" ], "offsets": [ [ 213, 235 ] ], "normalized": [] }, { "id": "PMID-1553573_T13", "type": "Cell", "text": [ "leukemic cells" ], "offsets": [ [ 441, 455 ] ], "normalized": [] }, { "id": "PMID-1553573_T14", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 467, 480 ] ], "normalized": [] }, { "id": "PMID-1553573_T17", "type": "Cell", "text": [ "bone marrow cells" ], "offsets": [ [ 647, 664 ] ], "normalized": [] }, { "id": "PMID-1553573_T19", "type": "Cancer", "text": [ "acute myeloid leukemia" ], "offsets": [ [ 687, 709 ] ], "normalized": [] }, { "id": "PMID-1553573_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 772, 777 ] ], "normalized": [] }, { "id": "PMID-1553573_T28", "type": "Cell", "text": [ "specimens" ], "offsets": [ [ 987, 996 ] ], "normalized": [] }, { "id": "PMID-1553573_T31", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1093, 1106 ] ], "normalized": [] }, { "id": "PMID-1553573_T44", "type": "Cell", "text": [ "leukemic blasts" ], "offsets": [ [ 1444, 1459 ] ], "normalized": [] }, { "id": "PMID-1553573_T46", "type": "Cell", "text": [ "clonogenic leukemic cells" ], "offsets": [ [ 1564, 1589 ] ], "normalized": [] }, { "id": "PMID-1553573_T51", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1660, 1673 ] ], "normalized": [] }, { "id": "PMID-1553573_T54", "type": "Cell", "text": [ "leukemic cells" ], "offsets": [ [ 1732, 1746 ] ], "normalized": [] }, { "id": "PMID-1553573_T56", "type": "Cell", "text": [ "clonogenic leukemic cells" ], "offsets": [ [ 1801, 1826 ] ], "normalized": [] }, { "id": "PMID-1553573_T57", "type": "Cell", "text": [ "CFU-L" ], "offsets": [ [ 1828, 1833 ] ], "normalized": [] } ]

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[ { "id": "PMID-11425277__text", "type": "abstract", "text": [ "Current prospects for controlling cancer growth with non-cytotoxic agents--nutrients, phytochemicals, herbal extracts, and available drugs.\nIn animal or cell culture studies, the growth and spread of cancer can be slowed by many nutrients, food factors, herbal extracts, and well-tolerated, available drugs that are still rarely used in the clinical management of cancer, in part because they seem unlikely to constitute definitive therapies in themselves. However, it is reasonable to expect that mechanistically complementary combinations of these measures could have a worthwhile impact on survival times and, when used as adjuvants, could improve the cure rates achievable with standard therapies. The therapeutic options available in this regard include measures that: down-regulate serum free IGF-I; suppress the synthesis of mevalonic acid and/or certain derivatives thereof; modulate arachidonate metabolism by inhibiting 5-lipoxygenase, 12-lipoxygenase, or COX-2; antagonize the activation of AP-1 transcription factors; promote the activation of PPAR-gamma transcription factors; and that suppress angiogenesis by additional mechanisms. Many of these measures appear suitable for use in cancer prevention.\n" ], "offsets": [ [ 0, 1216 ] ] } ]

[ { "id": "PMID-11425277_T1", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "PMID-11425277_T2", "type": "Cell", "text": [ "cell culture" ], "offsets": [ [ 153, 165 ] ], "normalized": [] }, { "id": "PMID-11425277_T3", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 200, 206 ] ], "normalized": [] }, { "id": "PMID-11425277_T4", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 364, 370 ] ], "normalized": [] }, { "id": "PMID-11425277_T5", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 788, 793 ] ], "normalized": [] }, { "id": "PMID-11425277_T14", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1197, 1203 ] ], "normalized": [] }, { "id": "PMID-11425277_T6", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 109, 117 ] ], "normalized": [] }, { "id": "PMID-11425277_T7", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 261, 269 ] ], "normalized": [] } ]

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[ { "id": "PMC-2959883-sec-06__text", "type": "sec", "text": [ "Data collection: CrystalClear (Rigaku/MSC, 2005 >); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 >); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 >); molecular graphics: ORTEPII (Johnson, 1976 >); software used to prepare material for publication: SHELXL97.\n" ], "offsets": [ [ 0, 354 ] ] } ]

[ { "id": "PMC-2959883-sec-06_T1", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 52, 56 ] ], "normalized": [] } ]

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[ { "id": "PMC-2845033-sec-09__text", "type": "sec", "text": [ "Applying A1C cut offs to the AusDiab population (4.6% undiagnosed diabetes)\nApplying the same cut offs, a total 75.9% of the AusDiab population had diabetes ruled in or ruled out (Fig. 1B), while the remaining 24.1% had impaired A1C. From those with impaired A1C, 69.3% had abnormal glucose status. For diabetes, A1C at 5.5% provided moderate sensitivity (83.5%) but high NPV (99.0%), since diabetes prevalence was lower in the AusDiab than in the MP population. A1C at 7.0% gave 100% specificity and 100% PPV. By dropping the cut off to 6.5%, specificity remained 99.9%, with PPV near 100%.\n" ], "offsets": [ [ 0, 592 ] ] } ]

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[ { "id": "PMID-15012488__text", "type": "abstract", "text": [ "Covariance structure analysis: statistical practice, theory, and directions.\nAlthough covariance structure analysis is used increasingly to analyze nonexperimental data, important statistical requirements for its proper use are frequently ignored. Valid conclusions about the adequacy of a model as an acceptable representation of data, which are based on goodness-of-fit test statistics and standard errors of parameter estimates, rely on the model estimation procedure being appropriate for the data. Using analogies to linear regression and anova, this review examines conditions under which conclusions drawn from various estimation methods will be correct and the consequences of ignoring these conditions. A distinction is made between estimation methods that are either correctly or incorrectly specified for the distribution of data being analyzed, and it is shown that valid conclusions are possible even under misspecification. A brief example illustrates the ideas. Internet access is given to a computer code for several methods that are not available in programs such as EQS or LISREL.\n" ], "offsets": [ [ 0, 1099 ] ] } ]

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[ { "id": "PMID-11836604__text", "type": "abstract", "text": [ "Prognostic significance of heat shock protein 27 (HSP27) in patients with oral squamous cell carcinoma. \nHeat shock proteins (HSPs) have been defined as proteins induced by heat shock and other environmental and pathophysiologic stress. Heat shock protein 27 (HSP27) is one of the small heat shock proteins. HSP27 is implicated in protein-protein interactions such as folding, translocation, and prevention of inappropriate protein aggregation. Many of their functions suggest that they play important roles in cancers. Archival tissues from 40 patients with oral squamous cell carcinoma who received primary surgical resection were examined for HSP27 by immunohistochemistry and correlated with clinical stage, lymph node metastasis, histological grade and survival period. HSP27 expression was positive staining (+) in 20 (50%), weak or negative staining (-) in 20 (50%) of total 40 cases. There was no correlation between HSP27 expression and clinical stage, lymph node metastasis and histological grade. However, when compared with clinicopathological features, the expression of HSP27 correlated inversely with survival period. This study suggests that the expression of HSP27 is frequently promoted in patients with oral squamous cell carcinoma and should be considered an independent prognostic factor of oral squamous cell carcinoma patients.\n" ], "offsets": [ [ 0, 1351 ] ] } ]

[ { "id": "PMID-11836604_T4", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 74, 102 ] ], "normalized": [] }, { "id": "PMID-11836604_T11", "type": "Cancer", "text": [ "cancers" ], "offsets": [ [ 511, 518 ] ], "normalized": [] }, { "id": "PMID-11836604_T12", "type": "Tissue", "text": [ "Archival tissues" ], "offsets": [ [ 520, 536 ] ], "normalized": [] }, { "id": "PMID-11836604_T14", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 559, 587 ] ], "normalized": [] }, { "id": "PMID-11836604_T16", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 712, 722 ] ], "normalized": [] }, { "id": "PMID-11836604_T19", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 962, 972 ] ], "normalized": [] }, { "id": "PMID-11836604_T23", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 1222, 1250 ] ], "normalized": [] }, { "id": "PMID-11836604_T24", "type": "Cancer", "text": [ "oral squamous cell carcinoma" ], "offsets": [ [ 1312, 1340 ] ], "normalized": [] } ]

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[ { "id": "PMID-15355640__text", "type": "abstract", "text": [ "[Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma]. \nOBJECTIVE: To investigate the expression of PTEN and loss of heterozygosity (LOH) of its epigenetic microsatellite in gastric carcinoma and explore their roles in progression of gastric carcinoma. METHODS: LOH of epigenetic microsatellites of PTEN (D10S541, D10S583 and D10S1687) in advanced gastric cancer was detected by PCR-SSCP. Expression of PTEN mRNA and protein in normal gastric mucosa and gastric cancer was evaluated by RT-PCR and SABC immunohistochemistry, respectively. The relationship between expression of PTEN mRNA and protein and lymph node metastasis or LOH of microsatellites was discussed. RESULTS: LOH of D10S541, D10S583 and D10S1687 was found in 37.5% (21/56) of advanced gastric cancers. The positive rates of PTEN mRNA expression were 80.4% (45/56), 45.5% (5/11) and 32.1% (18/56) in normal mucosa, early and advanced gastric carcinomas, respectively, while 78.6% (44/56), 44.5% (5/11) and 28.6% (16/56) at the protein level. PTEN mRNA and protein were less frequently expressed in early and advanced gastric carcinomas than that in normal gastric mucosa (P < 0.05). There was positive correlation between PTEN mRNA expression and LOH of microsatellites in advanced gastric carcinomas. PTEN protein expression paralleled with its mRNA expression (P < 0.05). The expression of PTEN mRNA and protein was negatively correlated with lymph node metastasis of advanced gastric carcinomas (P < 0.05). CONCLUSION: Down-regulated expression of PTEN gene is found in different stages of gastric carcinoma, and is closely correlated with LOH of its epigenetic microsatellites, which probably is its underlying molecular mechanisms. It suggests that altered PTEN gene contributes to tumorigenesis and progression of gastric carcinomas.\n" ], "offsets": [ [ 0, 1847 ] ] } ]

[ { "id": "PMID-15355640_T2", "type": "Cancer", "text": [ "gastric carcinoma" ], "offsets": [ [ 77, 94 ] ], "normalized": [] }, { "id": "PMID-15355640_T4", "type": "Cancer", "text": [ "gastric carcinoma" ], "offsets": [ [ 216, 233 ] ], "normalized": [] }, { "id": "PMID-15355640_T5", "type": "Cancer", "text": [ "gastric carcinoma" ], "offsets": [ [ 276, 293 ] ], "normalized": [] }, { "id": "PMID-15355640_T7", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 390, 404 ] ], "normalized": [] }, { "id": "PMID-15355640_T9", "type": "Multi-tissue_structure", "text": [ "gastric mucosa" ], "offsets": [ [ 477, 491 ] ], "normalized": [] }, { "id": "PMID-15355640_T10", "type": "Cancer", "text": [ "gastric cancer" ], "offsets": [ [ 496, 510 ] ], "normalized": [] }, { "id": "PMID-15355640_T12", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 645, 655 ] ], "normalized": [] }, { "id": "PMID-15355640_T13", "type": "Cancer", "text": [ "gastric cancers" ], "offsets": [ [ 793, 808 ] ], "normalized": [] }, { "id": "PMID-15355640_T15", "type": "Multi-tissue_structure", "text": [ "mucosa" ], "offsets": [ [ 914, 920 ] ], "normalized": [] }, { "id": "PMID-15355640_T16", "type": "Cancer", "text": [ "gastric carcinomas" ], "offsets": [ [ 941, 959 ] ], "normalized": [] }, { "id": "PMID-15355640_T18", "type": "Cancer", "text": [ "gastric carcinomas" ], "offsets": [ [ 1124, 1142 ] ], "normalized": [] }, { "id": "PMID-15355640_T19", "type": "Multi-tissue_structure", "text": [ "gastric mucosa" ], "offsets": [ [ 1163, 1177 ] ], "normalized": [] }, { "id": "PMID-15355640_T21", "type": "Cancer", "text": [ "gastric carcinomas" ], "offsets": [ [ 1289, 1307 ] ], "normalized": [] }, { "id": "PMID-15355640_T24", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 1452, 1462 ] ], "normalized": [] }, { "id": "PMID-15355640_T25", "type": "Cancer", "text": [ "gastric carcinomas" ], "offsets": [ [ 1486, 1504 ] ], "normalized": [] }, { "id": "PMID-15355640_T27", "type": "Cancer", "text": [ "gastric carcinoma" ], "offsets": [ [ 1600, 1617 ] ], "normalized": [] }, { "id": "PMID-15355640_T29", "type": "Cancer", "text": [ "gastric carcinomas" ], "offsets": [ [ 1827, 1845 ] ], "normalized": [] } ]

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[ { "id": "PMID-707591__text", "type": "abstract", "text": [ "Subretinal neovascularization following rubella retinopathy.\nA 17-year-old girl and an 11-year-old girl with rubella retinopathy had decreased vision in one eye secondary to subretinal neovascularization and hemorrhage. In both cases a disciform scar with permanent decrease in central vision resulted.\n" ], "offsets": [ [ 0, 303 ] ] } ]

[ { "id": "PMID-707591_T2", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 157, 160 ] ], "normalized": [] }, { "id": "PMID-707591_T4", "type": "Pathological_formation", "text": [ "scar" ], "offsets": [ [ 246, 250 ] ], "normalized": [] }, { "id": "PMID-707591_T5", "type": "Immaterial_anatomical_entity", "text": [ "Subretinal" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "PMID-707591_T6", "type": "Immaterial_anatomical_entity", "text": [ "subretinal" ], "offsets": [ [ 174, 184 ] ], "normalized": [] } ]

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[ { "id": "PMID-3993849__text", "type": "abstract", "text": [ "Management of the tortuous internal carotid artery.\nThe tortuous internal carotid artery as the basis of cerebral vascular insufficiency is a controversial entity, as such lesions frequently occur without neurologic symptoms. However, some tortuous vessels are associated with significant carotid atherosclerotic disease requiring a specific surgical approach. This formed the basis of our report. Symptoms of cerebrovascular insufficiency in association with a tortuous internal carotid artery was encountered in 27 of 853 carotid endarterectomies over a 22 year period. Stenosis of hemodynamic significance was noted in nine patients and irregularities or ulceration were noted in the rest. With the standard technique of carotid endarterectomy, removal of plaque from a tortuous vessel leads to loss of the stenting effect provided by the plaque such that angulation occlusion is likely to occur. The optimal reconstruction in our experience is eversion endarterectomy by transection and lower reimplantation of the internal carotid artery on the common carotid artery. Our experience with 17 such procedures in 15 patients has been presented.\n" ], "offsets": [ [ 0, 1147 ] ] } ]

[ { "id": "PMID-3993849_T1", "type": "Multi-tissue_structure", "text": [ "tortuous internal carotid artery" ], "offsets": [ [ 18, 50 ] ], "normalized": [] }, { "id": "PMID-3993849_T2", "type": "Multi-tissue_structure", "text": [ "tortuous internal carotid artery" ], "offsets": [ [ 56, 88 ] ], "normalized": [] }, { "id": "PMID-3993849_T3", "type": "Multi-tissue_structure", "text": [ "cerebral vascular" ], "offsets": [ [ 105, 122 ] ], "normalized": [] }, { "id": "PMID-3993849_T4", "type": "Pathological_formation", "text": [ "lesions" ], "offsets": [ [ 172, 179 ] ], "normalized": [] }, { "id": "PMID-3993849_T5", "type": "Multi-tissue_structure", "text": [ "tortuous vessels" ], "offsets": [ [ 240, 256 ] ], "normalized": [] }, { "id": "PMID-3993849_T6", "type": "Multi-tissue_structure", "text": [ "cerebrovascular" ], "offsets": [ [ 410, 425 ] ], "normalized": [] }, { "id": "PMID-3993849_T7", "type": "Multi-tissue_structure", "text": [ "tortuous internal carotid artery" ], "offsets": [ [ 462, 494 ] ], "normalized": [] }, { "id": "PMID-3993849_T8", "type": "Multi-tissue_structure", "text": [ "carotid" ], "offsets": [ [ 524, 531 ] ], "normalized": [] }, { "id": "PMID-3993849_T9", "type": "Multi-tissue_structure", "text": [ "carotid" ], "offsets": [ [ 724, 731 ] ], "normalized": [] }, { "id": "PMID-3993849_T10", "type": "Multi-tissue_structure", "text": [ "tortuous vessel" ], "offsets": [ [ 773, 788 ] ], "normalized": [] }, { "id": "PMID-3993849_T11", "type": "Pathological_formation", "text": [ "plaque" ], "offsets": [ [ 759, 765 ] ], "normalized": [] }, { "id": "PMID-3993849_T12", "type": "Pathological_formation", "text": [ "plaque" ], "offsets": [ [ 842, 848 ] ], "normalized": [] }, { "id": "PMID-3993849_T13", "type": "Multi-tissue_structure", "text": [ "internal carotid artery" ], "offsets": [ [ 1019, 1042 ] ], "normalized": [] }, { "id": "PMID-3993849_T14", "type": "Multi-tissue_structure", "text": [ "common carotid artery" ], "offsets": [ [ 1050, 1071 ] ], "normalized": [] }, { "id": "PMID-3993849_T15", "type": "Multi-tissue_structure", "text": [ "carotid" ], "offsets": [ [ 289, 296 ] ], "normalized": [] }, { "id": "PMID-3993849_T16", "type": "Anatomical_system", "text": [ "neurologic" ], "offsets": [ [ 205, 215 ] ], "normalized": [] } ]

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[ { "id": "PMID-10816661__text", "type": "abstract", "text": [ "Alpha-melanocyte-stimulating hormone modulates activation of NF-kappa B and AP-1 and secretion of interleukin-8 in human dermal fibroblasts.\nAlpha-melanocyte-stimulating hormone (alpha-MSH) has evolved as a mediator of diverse biological activities in an ever-growing number of non-melanocytic cell types. One mechanism by which alpha-MSH exerts its effects is modulation of AP-1 and NF-kappa B. These two transcription factors also play an important role in fibroblasts, in extracellular matrix composition, and in cytokine expression. By use of electric mobility shift assays, we demonstrate that alpha-MSH (10(-6) to 10(-14) M) activates AP-1 in human dermal fibroblasts, whereas coincubation with interleukin-1 beta (IL-1 beta) results in suppression of its activation. alpha-MSH also induces activation of NF-kappa B but does not modulate DNA binding on costimulation with IL-1 beta. Since AP-1 and NF-kappa B are key elements in controlling interleukin-8 (IL-8) transcription, human fibroblasts were treated with alpha-MSH and IL-1 beta for 24 hours, and cytokine levels in the supernatants were measured by ELISA. alpha-MSH alone had little effect, whereas coincubation with IL-1 beta led to marked downregulation of IL-8 secretion (at most 288 +/- 152 ng/mL) when compared to treatment with IL-1 beta alone (919 +/- 157 ng/mL). Our results indicate that alpha-MSH exerts modulatory effects on the activation of NF-kappa B and AP-1, and that it can regulate chemokine secretion in human dermal fibroblasts. These effects of alpha-MSH may have important regulatory functions in extracellular matrix composition, wound healing, or angiogenesis.\n" ], "offsets": [ [ 0, 1650 ] ] } ]

[ { "id": "PMID-10816661_T6", "type": "Cell", "text": [ "dermal fibroblasts" ], "offsets": [ [ 121, 139 ] ], "normalized": [] }, { "id": "PMID-10816661_T9", "type": "Cell", "text": [ "non-melanocytic cell" ], "offsets": [ [ 278, 298 ] ], "normalized": [] }, { "id": "PMID-10816661_T13", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "PMID-10816661_T14", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 475, 495 ] ], "normalized": [] }, { "id": "PMID-10816661_T18", "type": "Cell", "text": [ "dermal fibroblasts" ], "offsets": [ [ 655, 673 ] ], "normalized": [] }, { "id": "PMID-10816661_T30", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 989, 1000 ] ], "normalized": [] }, { "id": "PMID-10816661_T41", "type": "Cell", "text": [ "dermal fibroblasts" ], "offsets": [ [ 1494, 1512 ] ], "normalized": [] }, { "id": "PMID-10816661_T43", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 1584, 1604 ] ], "normalized": [] }, { "id": "PMID-10816661_T44", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 1618, 1623 ] ], "normalized": [] }, { "id": "PMID-10816661_T1", "type": "Organism_substance", "text": [ "supernatants" ], "offsets": [ [ 1084, 1096 ] ], "normalized": [] } ]

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[ { "id": "PMID-11381168__text", "type": "abstract", "text": [ "Effects of morphological patterning on endothelial cell migration.\nThe migration of vascular endothelial cells (ECs) plays an important role in vascular remodeling. Here we studied the effects of cell morphology on the migration of bovine aortic ECs by culturing cells on micropatterned strips of collagen matrix (60-, 30-, and 15-microm wide). The spreading areas of the cells on 15- and 30-microm wide strips were 30% lower than those on 60-microm wide strips and unpatterned collagen. The cells on 15-microm wide strips completely aligned in the direction of the strip, and had significantly lower shape index than those in all other groups. On strips of all widths, ECs tended to migrate in the direction of strips. ECs on 15-microm wide strips had highest speed, particularly in the direction of the strip. Vinculin staining showed that the leading edge of ECs on 15-microm wide strips had focal adhesions that were oriented with their lamellipodial protrusion and the direction of cell migration; this arrangement of the focal adhesions may promote EC migration. The present study provides direct evidence on the role of cell morphology in EC migration, and will help us to understand the mechanisms of EC migration during angiogenesis and wound healing.\n" ], "offsets": [ [ 0, 1261 ] ] } ]

[ { "id": "PMID-11381168_T1", "type": "Cell", "text": [ "endothelial cell" ], "offsets": [ [ 39, 55 ] ], "normalized": [] }, { "id": "PMID-11381168_T2", "type": "Cell", "text": [ "vascular endothelial cells" ], "offsets": [ [ 84, 110 ] ], "normalized": [] }, { "id": "PMID-11381168_T3", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 112, 115 ] ], "normalized": [] }, { "id": "PMID-11381168_T4", "type": "Multi-tissue_structure", "text": [ "vascular" ], "offsets": [ [ 144, 152 ] ], "normalized": [] }, { "id": "PMID-11381168_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 196, 200 ] ], "normalized": [] }, { "id": "PMID-11381168_T7", "type": "Cell", "text": [ "aortic ECs" ], "offsets": [ [ 239, 249 ] ], "normalized": [] }, { "id": "PMID-11381168_T8", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 263, 268 ] ], "normalized": [] }, { "id": "PMID-11381168_T10", "type": "Cellular_component", "text": [ "matrix" ], "offsets": [ [ 306, 312 ] ], "normalized": [] }, { "id": "PMID-11381168_T11", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 372, 377 ] ], "normalized": [] }, { "id": "PMID-11381168_T13", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 492, 497 ] ], "normalized": [] }, { "id": "PMID-11381168_T14", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 670, 673 ] ], "normalized": [] }, { "id": "PMID-11381168_T15", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 720, 723 ] ], "normalized": [] }, { "id": "PMID-11381168_T17", "type": "Cell", "text": [ "ECs" ], "offsets": [ [ 862, 865 ] ], "normalized": [] }, { "id": "PMID-11381168_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 987, 991 ] ], "normalized": [] }, { "id": "PMID-11381168_T19", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1055, 1057 ] ], "normalized": [] }, { "id": "PMID-11381168_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1127, 1131 ] ], "normalized": [] }, { "id": "PMID-11381168_T21", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1146, 1148 ] ], "normalized": [] }, { "id": "PMID-11381168_T22", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 1209, 1211 ] ], "normalized": [] }, { "id": "PMID-11381168_T23", "type": "Pathological_formation", "text": [ "wound" ], "offsets": [ [ 1246, 1251 ] ], "normalized": [] }, { "id": "PMID-11381168_T39", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 895, 910 ] ], "normalized": [] }, { "id": "PMID-11381168_T40", "type": "Cellular_component", "text": [ "focal adhesions" ], "offsets": [ [ 1027, 1042 ] ], "normalized": [] } ]

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[ { "id": "PMID-11107120__text", "type": "abstract", "text": [ "p75 mediated apoptosis in neuroblastoma cells is inhibited by expression of TrkA. \nBACKGROUND: Neurotrophins mediate their effects by binding to members of the Trk family of receptor tyrosine kinases and to the low-affinity nerve growth factor receptor p75. Nerve growth factor (NGF) has been demonstrated to support survival and differentiation of neuroblastoma (NB) cells by activation of the TrkA receptor. The p75 receptor belongs to the tumor necrosis factor (TNF) family of death receptors and has been suggested as a receptor that mediates apoptosis in neuronal and NB cells. PROCEDURE: To investigate the effect of p75 expression in NB, we transfected the p75 cDNA into SH-SY5Y cells, an NB cell line lacking expression of both p75 and TrkA. RESULTS: Cell clones expressing elevated levels of p75 showed a high degree of apoptosis even in 10% serum-supplemented medium. Apoptotic signaling by p75 was ligand-independent and only partly caspase-dependent. The level of apoptosis correlated directly with the expression level of the receptor, indicating that p75 may activate the cell death program directly. However, additional transfection of TrkA into SY5Y-p75 cells resulted in a significantly reduced rate of apoptosis even in the absence of NGF. CONCLUSIONS: Thus, expression of the TrkA receptor itself inhibits p75 mediated apoptosis in NB cells.\n" ], "offsets": [ [ 0, 1361 ] ] } ]

[ { "id": "PMID-11107120_T2", "type": "Cell", "text": [ "neuroblastoma cells" ], "offsets": [ [ 26, 45 ] ], "normalized": [] }, { "id": "PMID-11107120_T9", "type": "Cell", "text": [ "neuroblastoma (NB) cells" ], "offsets": [ [ 349, 373 ] ], "normalized": [] }, { "id": "PMID-11107120_T14", "type": "Cell", "text": [ "neuronal" ], "offsets": [ [ 560, 568 ] ], "normalized": [] }, { "id": "PMID-11107120_T15", "type": "Cell", "text": [ "NB cells" ], "offsets": [ [ 573, 581 ] ], "normalized": [] }, { "id": "PMID-11107120_T17", "type": "Cancer", "text": [ "NB" ], "offsets": [ [ 641, 643 ] ], "normalized": [] }, { "id": "PMID-11107120_T19", "type": "Cell", "text": [ "SH-SY5Y cells" ], "offsets": [ [ 678, 691 ] ], "normalized": [] }, { "id": "PMID-11107120_T20", "type": "Cell", "text": [ "NB cell line" ], "offsets": [ [ 696, 708 ] ], "normalized": [] }, { "id": "PMID-11107120_T23", "type": "Cell", "text": [ "Cell clones" ], "offsets": [ [ 759, 770 ] ], "normalized": [] }, { "id": "PMID-11107120_T25", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 851, 856 ] ], "normalized": [] }, { "id": "PMID-11107120_T29", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1086, 1090 ] ], "normalized": [] }, { "id": "PMID-11107120_T32", "type": "Cell", "text": [ "SY5Y-p75 cells" ], "offsets": [ [ 1161, 1175 ] ], "normalized": [] }, { "id": "PMID-11107120_T37", "type": "Cell", "text": [ "NB cells" ], "offsets": [ [ 1351, 1359 ] ], "normalized": [] } ]

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[ { "id": "PMID-12920663__text", "type": "abstract", "text": [ "Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study.\nRetinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy.\n" ], "offsets": [ [ 0, 1947 ] ] } ]

[ { "id": "PMID-12920663_T1", "type": "Organ", "text": [ "ocular" ], "offsets": [ [ 81, 87 ] ], "normalized": [] }, { "id": "PMID-12920663_T4", "type": "Organism_substance", "text": [ "aqueous humor" ], "offsets": [ [ 154, 167 ] ], "normalized": [] }, { "id": "PMID-12920663_T5", "type": "Tissue", "text": [ "microvascular" ], "offsets": [ [ 215, 228 ] ], "normalized": [] }, { "id": "PMID-12920663_T6", "type": "Organism_substance", "text": [ "aqueous humor" ], "offsets": [ [ 413, 426 ] ], "normalized": [] }, { "id": "PMID-12920663_T7", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 434, 437 ] ], "normalized": [] }, { "id": "PMID-12920663_T8", "type": "Organism_substance", "text": [ "Aqueous humor" ], "offsets": [ [ 439, 452 ] ], "normalized": [] }, { "id": "PMID-12920663_T15", "type": "Organism_substance", "text": [ "aqueous humor" ], "offsets": [ [ 747, 760 ] ], "normalized": [] }, { "id": "PMID-12920663_T16", "type": "Cell", "text": [ "capillary endothelial cells" ], "offsets": [ [ 820, 847 ] ], "normalized": [] }, { "id": "PMID-12920663_T17", "type": "Organism_substance", "text": [ "aqueous fluid" ], "offsets": [ [ 856, 869 ] ], "normalized": [] }, { "id": "PMID-12920663_T30", "type": "Organism_substance", "text": [ "aqueous humor" ], "offsets": [ [ 1837, 1850 ] ], "normalized": [] }, { "id": "PMID-12920663_T52", "type": "Organ", "text": [ "ocular" ], "offsets": [ [ 1681, 1687 ] ], "normalized": [] } ]

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[ { "id": "PMID-8691230__text", "type": "abstract", "text": [ "Referral bias among health workers in studies using hospitalization as a proxy measure of the underlying incidence rate.\nContacts with health services like hospitals or general practitioners are usually the only available proxy measure of incidence of disease in studies based on secondary data and differential referrals or care-seeking behavior often bias such proxy measures. In former analyses based on the Occupational Hospitalization Register in Denmark assisting nurses had high Standardized Hospitalization Ratios for many diseases. It was, however, suspected that it fully or partly was due to a referral bias or self-selection to hospital treatment rather than exposures to occupational hazards. The aim of the present study is to evaluate the referral bias hypothesis by comparing hospitalization and mortality data for health workers for a disease category with a high mortality. Cohorts of all gainfully employed 20- to 59-year-old Danes were formed in order to compare Standardized Mortality Ratios and Standardized Hospitalization Ratios of ischemic heart disease (IHD) in occupational groups. The follow-up period was 10 years. For most of the investigated occupational groups a similar disease pattern was found whether hospitalization or death was used as the outcome measure. In \"nurse assistants\" a statistically significant higher risk was, however, found using hospitalization due to IHD as the end point rather than mortality. Additional analysis did not support the hypothesis that the finding could be explained by differentiated hospitalization due to social factors. The true incidence rates of the disease need not be equally well described by proxy measures such as hospitalization diagnosis or death diagnosis in all occupational groups. Differential access to medical treatment in some groups may lead to bias when hospital data are used as proxy measures for the underlying incidence rates.\n" ], "offsets": [ [ 0, 1923 ] ] } ]

[ { "id": "PMID-8691230_T1", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [] } ]

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[ { "id": "PMID-11255762__text", "type": "abstract", "text": [ "[Study of fungus polysaccharides compounds (FPC) in inducing the apoptosis of liver cancer cell Bel-7402]. \nTo observe the influence of fungus polysaccharides compounds (FPC) in inducing human liver cancer cell Bel-7402 apoptosis in cell cultivating in vitro, the authors analyzed tumor inhibitive gene P53 expression in Bel-7402 apoptosis by applying double immuno-marker. The result showed that the multilevel of FPC could all apparently induce Bel-7402 apoptosis. With the enhancement of FPC concentration, the authors observed chromatin condensation in some phases companying with the characteristic apoptosis. In the meantime, it could also greatly reduce the G1 and S, with obviously dose-response relationship. The percentage of cell apoptosis increased with the enhancing of concentration. In the high-level group the authors found typical DNA ladder eletrophoresis stripe. The result showed that the mechanism of the FPC antineoplastic effect had an intimate relation with its induction to apoptosis and that the result of FPC inducing tumor cell apoptosis had the character of P53 independence.\n" ], "offsets": [ [ 0, 1105 ] ] } ]

[ { "id": "PMID-11255762_T3", "type": "Cell", "text": [ "liver cancer cell Bel-7402]" ], "offsets": [ [ 78, 105 ] ], "normalized": [] }, { "id": "PMID-11255762_T7", "type": "Cell", "text": [ "liver cancer cell Bel-7402" ], "offsets": [ [ 193, 219 ] ], "normalized": [] }, { "id": "PMID-11255762_T8", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 233, 237 ] ], "normalized": [] }, { "id": "PMID-11255762_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 281, 286 ] ], "normalized": [] }, { "id": "PMID-11255762_T11", "type": "Cell", "text": [ "Bel-7402" ], "offsets": [ [ 321, 329 ] ], "normalized": [] }, { "id": "PMID-11255762_T13", "type": "Cell", "text": [ "Bel-7402" ], "offsets": [ [ 447, 455 ] ], "normalized": [] }, { "id": "PMID-11255762_T15", "type": "Cellular_component", "text": [ "chromatin" ], "offsets": [ [ 531, 540 ] ], "normalized": [] }, { "id": "PMID-11255762_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "PMID-11255762_T20", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1045, 1055 ] ], "normalized": [] }, { "id": "PMID-11255762_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 934, 944 ] ], "normalized": [] } ]

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[ { "id": "PMID-18319331__text", "type": "abstract", "text": [ "Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma.\nWe hypothesized that signaling through multiple mitogen-activated protein kinase (MAPK) kinase (MKK) pathways is essential for the growth and vascularization of soft-tissue sarcomas, which are malignant tumors derived from mesenchymal tissues. We tested this using HT-1080, NCI, and Shac fibrosarcoma-derived cell lines and anthrax lethal toxin (LeTx), a bacterial toxin that inactivates MKKs. Western blots confirmed that LeTx treatment reduced the levels of phosphorylated extracellular signal-regulated kinase and p38 MAPK in vitro. Although short treatments with LeTx only modestly affected cell proliferation, sustained treatment markedly reduced cell numbers. LeTx also substantially inhibited the extracellular release of angioproliferative factors including vascular endothelial growth factor, interleukin-8, and basic fibroblast growth factor. Similar results were obtained with cell lines derived from malignant fibrous histiocytomas, leiomyosarcomas, and liposarcomas. In vivo, LeTx decreased MAPK activity and blocked fibrosarcoma growth. Growth inhibition correlated with decreased cellular proliferation and extensive necrosis, and it was accompanied by a decrease in tumor mean vessel density as well as a reduction in serum expression of angioproliferative cytokines. Vital imaging using high-resolution ultrasound enhanced with contrast microbubbles revealed that the effects of LeTx on tumor perfusion were remarkably rapid ( less than 24 h) and resulted in a marked reduction of perfusion within the tumor but not in nontumor tissues. These results are consistent with our initial hypothesis and lead us to propose that MKK inhibition by LeTx is a broadly effective strategy for targeting neovascularization in fibrosarcomas and other similar proliferative lesions.\n" ], "offsets": [ [ 0, 1888 ] ] } ]

[ { "id": "PMID-18319331_T2", "type": "Cancer", "text": [ "fibrosarcoma" ], "offsets": [ [ 89, 101 ] ], "normalized": [] }, { "id": "PMID-18319331_T5", "type": "Cancer", "text": [ "soft-tissue sarcomas" ], "offsets": [ [ 264, 284 ] ], "normalized": [] }, { "id": "PMID-18319331_T6", "type": "Cancer", "text": [ "malignant tumors" ], "offsets": [ [ 296, 312 ] ], "normalized": [] }, { "id": "PMID-18319331_T7", "type": "Tissue", "text": [ "mesenchymal tissues" ], "offsets": [ [ 326, 345 ] ], "normalized": [] }, { "id": "PMID-18319331_T8", "type": "Cell", "text": [ "HT-1080" ], "offsets": [ [ 368, 375 ] ], "normalized": [] }, { "id": "PMID-18319331_T9", "type": "Cell", "text": [ "NCI" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "PMID-18319331_T10", "type": "Cell", "text": [ "Shac fibrosarcoma-derived cell lines" ], "offsets": [ [ 386, 422 ] ], "normalized": [] }, { "id": "PMID-18319331_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 698, 702 ] ], "normalized": [] }, { "id": "PMID-18319331_T20", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 755, 759 ] ], "normalized": [] }, { "id": "PMID-18319331_T22", "type": "Immaterial_anatomical_entity", "text": [ "extracellular" ], "offsets": [ [ 807, 820 ] ], "normalized": [] }, { "id": "PMID-18319331_T26", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 991, 1001 ] ], "normalized": [] }, { "id": "PMID-18319331_T27", "type": "Cancer", "text": [ "malignant fibrous histiocytomas" ], "offsets": [ [ 1015, 1046 ] ], "normalized": [] }, { "id": "PMID-18319331_T28", "type": "Cancer", "text": [ "leiomyosarcomas" ], "offsets": [ [ 1048, 1063 ] ], "normalized": [] }, { "id": "PMID-18319331_T29", "type": "Cancer", "text": [ "liposarcomas" ], "offsets": [ [ 1069, 1081 ] ], "normalized": [] }, { "id": "PMID-18319331_T32", "type": "Cancer", "text": [ "fibrosarcoma" ], "offsets": [ [ 1133, 1145 ] ], "normalized": [] }, { "id": "PMID-18319331_T33", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1198, 1206 ] ], "normalized": [] }, { "id": "PMID-18319331_T34", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1285, 1290 ] ], "normalized": [] }, { "id": "PMID-18319331_T35", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1296, 1302 ] ], "normalized": [] }, { "id": "PMID-18319331_T36", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1337, 1342 ] ], "normalized": [] }, { "id": "PMID-18319331_T38", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1507, 1512 ] ], "normalized": [] }, { "id": "PMID-18319331_T39", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1622, 1627 ] ], "normalized": [] }, { "id": "PMID-18319331_T40", "type": "Tissue", "text": [ "nontumor tissues" ], "offsets": [ [ 1639, 1655 ] ], "normalized": [] }, { "id": "PMID-18319331_T43", "type": "Cancer", "text": [ "fibrosarcomas" ], "offsets": [ [ 1833, 1846 ] ], "normalized": [] }, { "id": "PMID-18319331_T44", "type": "Cancer", "text": [ "proliferative lesions" ], "offsets": [ [ 1865, 1886 ] ], "normalized": [] } ]

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[ { "id": "PMID-19080335__text", "type": "abstract", "text": [ "Effect of transplanted mesenchymal stem cells from rats of different ages on the improvement of heart function after acute myocardial infarction.\nBACKGROUND: Mesenchymal stem cells (MSCs) transplantation is of therapeutic potential after ischemic injury in both experimental and clinical studies. Clinically, elderly patients are more vulnerable to acute myocardial infarction (AMI). But little is known about the characteristics of young donor-derived MSCs transplanted to old patients with AMI. The present study was designed to investigate the effect of transplanted MSCs from rats of different ages on the improvement of heart function after AMI. METHODS: MSCs from Sprague-Dawley (SD) rats were isolated and cultured in vitro. The apoptosis characteristics of MSCs were observed under conditions of ischemia and anoxia. SD rats underwent MI received intramyocardial injection of MSCs from young donor rats (n = 8), old donor rats (n = 8), respectively. AMI control group received equal volume physiological saline. Immunofluorescence was used to observe the differentiation of the grafted cells into cardiomyocytes. Four weeks after cell transplantation, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry for vascular endothelial growth factor (VEGF), VIII-factor immunohistochemistry for vessel density, TUNEL, caspase-3 for cardiomyocyte apoptosis, echocardiography and hemodynamic detection for heart function were performed. RESULTS: The apoptosis rate of the old donor-derived MSCs group was significantly higher than that of the young donor-derived MSCs group under conditions of ischemia and anoxia (P less than 0.05). Engrafted MSCs survived, proliferated and differentiated into myocardium-like cells. VEGF gene expression and capillary density in the old donor-derived group were lower than those in the young donor-derived group but higher than those in the control group (P less than 0.05). The transplantation of old donor-derived MSCs attenuated apoptosis of cardiomyocytes in the peri-infarct region compared with the control group and the effect was elevated in young donor-derived MSCs (P less than 0.05). The heart functions (left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS)) were improved more significantly in the old donor-derived MSCs group than in the control group and the heart function in the young donor-derived MSCs group further improved (P less than 0.05). CONCLUSIONS: Young donor-derived MSCs can improve heart function significantly through angiogenesis and decreasing cardiomyocyte apoptosis when transplanted to the infarcted area.\n" ], "offsets": [ [ 0, 2648 ] ] } ]

[ { "id": "PMID-19080335_T1", "type": "Cell", "text": [ "mesenchymal stem cells" ], "offsets": [ [ 23, 45 ] ], "normalized": [] }, { "id": "PMID-19080335_T3", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "PMID-19080335_T4", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 123, 133 ] ], "normalized": [] }, { "id": "PMID-19080335_T5", "type": "Cell", "text": [ "Mesenchymal stem cells" ], "offsets": [ [ 158, 180 ] ], "normalized": [] }, { "id": "PMID-19080335_T6", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 182, 186 ] ], "normalized": [] }, { "id": "PMID-19080335_T8", "type": "Multi-tissue_structure", "text": [ "myocardial" ], "offsets": [ [ 355, 365 ] ], "normalized": [] }, { "id": "PMID-19080335_T9", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 453, 457 ] ], "normalized": [] }, { "id": "PMID-19080335_T11", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-19080335_T13", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 625, 630 ] ], "normalized": [] }, { "id": "PMID-19080335_T14", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 660, 664 ] ], "normalized": [] }, { "id": "PMID-19080335_T16", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 765, 769 ] ], "normalized": [] }, { "id": "PMID-19080335_T18", "type": "Immaterial_anatomical_entity", "text": [ "intramyocardial" ], "offsets": [ [ 855, 870 ] ], "normalized": [] }, { "id": "PMID-19080335_T19", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 884, 888 ] ], "normalized": [] }, { "id": "PMID-19080335_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1094, 1099 ] ], "normalized": [] }, { "id": "PMID-19080335_T23", "type": "Cell", "text": [ "cardiomyocytes" ], "offsets": [ [ 1105, 1119 ] ], "normalized": [] }, { "id": "PMID-19080335_T24", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1138, 1142 ] ], "normalized": [] }, { "id": "PMID-19080335_T28", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1326, 1332 ] ], "normalized": [] }, { "id": "PMID-19080335_T30", "type": "Cell", "text": [ "cardiomyocyte" ], "offsets": [ [ 1363, 1376 ] ], "normalized": [] }, { "id": "PMID-19080335_T31", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 1435, 1440 ] ], "normalized": [] }, { "id": "PMID-19080335_T32", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "PMID-19080335_T33", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 1592, 1596 ] ], "normalized": [] }, { "id": "PMID-19080335_T34", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 1675, 1679 ] ], "normalized": [] }, { "id": "PMID-19080335_T35", "type": "Cell", "text": [ "myocardium-like cells" ], "offsets": [ [ 1727, 1748 ] ], "normalized": [] }, { "id": "PMID-19080335_T37", "type": "Tissue", "text": [ "capillary" ], "offsets": [ [ 1775, 1784 ] ], "normalized": [] }, { "id": "PMID-19080335_T38", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 1985, 1989 ] ], "normalized": [] }, { "id": "PMID-19080335_T39", "type": "Cell", "text": [ "cardiomyocytes" ], "offsets": [ [ 2014, 2028 ] ], "normalized": [] }, { "id": "PMID-19080335_T40", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 2139, 2143 ] ], "normalized": [] }, { "id": "PMID-19080335_T41", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 2170, 2175 ] ], "normalized": [] }, { "id": "PMID-19080335_T42", "type": "Multi-tissue_structure", "text": [ "left ventricle" ], "offsets": [ [ 2187, 2201 ] ], "normalized": [] }, { "id": "PMID-19080335_T43", "type": "Multi-tissue_structure", "text": [ "left ventricle" ], "offsets": [ [ 2228, 2242 ] ], "normalized": [] }, { "id": "PMID-19080335_T44", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 2331, 2335 ] ], "normalized": [] }, { "id": "PMID-19080335_T45", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 2376, 2381 ] ], "normalized": [] }, { "id": "PMID-19080335_T46", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 2418, 2422 ] ], "normalized": [] }, { "id": "PMID-19080335_T47", "type": "Cell", "text": [ "MSCs" ], "offsets": [ [ 2501, 2505 ] ], "normalized": [] }, { "id": "PMID-19080335_T48", "type": "Organ", "text": [ "heart" ], "offsets": [ [ 2518, 2523 ] ], "normalized": [] }, { "id": "PMID-19080335_T49", "type": "Cell", "text": [ "cardiomyocyte" ], "offsets": [ [ 2583, 2596 ] ], "normalized": [] }, { "id": "PMID-19080335_T2", "type": "Multi-tissue_structure", "text": [ "area" ], "offsets": [ [ 2642, 2646 ] ], "normalized": [] } ]

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[ { "id": "PMID-15574223__text", "type": "abstract", "text": [ "Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study. \nOBJECTIVE: Dependence on glycolysis is a hallmark of malignant tumors. As a consequence, these tumors generate more lactate, which is effluxed from cells by monocarboxylate transporters (MCTs). We hypothesized that 1) MCT expression in malignant tumors may differ from normal tissue in quantity, isoform, or both; and 2) silencing MCT expression would induce intracellular acidification, resulting in decreased proliferation and/or increased cell death. METHODS: We quantified expression of MCT isoforms in human glioblastoma multiforme and glioma-derived cells lines by Western blot analysis. MCTs that were abundant or specific to glioma then were targeted in the model U-87 MG glioma cell line via small interfering ribonucleic acid-mediated gene silencing and tested for inhibition of lactate efflux, intracellular pH changes, reduced proliferation, and/or induction of cell death. RESULTS: MCT 1 and 2 were the primary isoforms expressed in human glioblastoma multiforme and glioma-derived cell lines. In contrast, MCT 3 was the predominantly expressed isoform in normal brain. Small interfering ribonucleic acid specific for MCT 1 and 2 reduced expression of these isoforms in U-87 MG cells to barely detectable levels and reduced lactate efflux by 30% individually and 85% in combination, with a concomitant decrease of intracellular pH by 0.6 units (a fourfold increase in intracellular H(+)). Prolonged silencing of both MCTs reduced viability by 75% individually and 92% in combination, as measured by both phenotypic and flow cytometric analyses. CONCLUSION: MCT targeting significantly reduced the viability of U-87 MG cells mediated by both apoptosis and necrosis. This indicates that the strategy may be a useful therapeutic avenue for treatment of patients with malignant glioma.\n" ], "offsets": [ [ 0, 1960 ] ] } ]

[ { "id": "PMID-15574223_T2", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 113, 117 ] ], "normalized": [] }, { "id": "PMID-15574223_T3", "type": "Cancer", "text": [ "malignant glioma" ], "offsets": [ [ 127, 143 ] ], "normalized": [] }, { "id": "PMID-15574223_T4", "type": "Cancer", "text": [ "malignant tumors" ], "offsets": [ [ 218, 234 ] ], "normalized": [] }, { "id": "PMID-15574223_T5", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "PMID-15574223_T7", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 313, 318 ] ], "normalized": [] }, { "id": "PMID-15574223_T11", "type": "Cancer", "text": [ "malignant tumors" ], "offsets": [ [ 401, 417 ] ], "normalized": [] }, { "id": "PMID-15574223_T12", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 441, 447 ] ], "normalized": [] }, { "id": "PMID-15574223_T14", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 524, 537 ] ], "normalized": [] }, { "id": "PMID-15574223_T15", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 607, 611 ] ], "normalized": [] }, { "id": "PMID-15574223_T18", "type": "Cell", "text": [ "glioblastoma multiforme" ], "offsets": [ [ 678, 701 ] ], "normalized": [] }, { "id": "PMID-15574223_T19", "type": "Cell", "text": [ "glioma-derived cells lines" ], "offsets": [ [ 706, 732 ] ], "normalized": [] }, { "id": "PMID-15574223_T21", "type": "Cancer", "text": [ "glioma" ], "offsets": [ [ 798, 804 ] ], "normalized": [] }, { "id": "PMID-15574223_T22", "type": "Cell", "text": [ "U-87 MG glioma cell line" ], "offsets": [ [ 837, 861 ] ], "normalized": [] }, { "id": "PMID-15574223_T24", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 970, 983 ] ], "normalized": [] }, { "id": "PMID-15574223_T25", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1039, 1043 ] ], "normalized": [] }, { "id": "PMID-15574223_T29", "type": "Cell", "text": [ "glioblastoma multiforme" ], "offsets": [ [ 1117, 1140 ] ], "normalized": [] }, { "id": "PMID-15574223_T30", "type": "Cell", "text": [ "glioma-derived cell lines" ], "offsets": [ [ 1145, 1170 ] ], "normalized": [] }, { "id": "PMID-15574223_T32", "type": "Organ", "text": [ "brain" ], "offsets": [ [ 1241, 1246 ] ], "normalized": [] }, { "id": "PMID-15574223_T35", "type": "Cell", "text": [ "U-87 MG cells" ], "offsets": [ [ 1348, 1361 ] ], "normalized": [] }, { "id": "PMID-15574223_T37", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1492, 1505 ] ], "normalized": [] }, { "id": "PMID-15574223_T38", "type": "Immaterial_anatomical_entity", "text": [ "intracellular" ], "offsets": [ [ 1546, 1559 ] ], "normalized": [] }, { "id": "PMID-15574223_T41", "type": "Cell", "text": [ "U-87 MG cells" ], "offsets": [ [ 1788, 1801 ] ], "normalized": [] }, { "id": "PMID-15574223_T43", "type": "Cancer", "text": [ "malignant glioma" ], "offsets": [ [ 1942, 1958 ] ], "normalized": [] } ]

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[ { "id": "PMID-19389366__text", "type": "abstract", "text": [ "Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo. \nThe polycomb gene Bmi-1 is required for the self-renewal of stem cells from diverse tissues, including the central nervous system (CNS). Bmi-1 expression is elevated in most human gliomas, irrespective of grade, raising the question of whether Bmi-1 over-expression is sufficient to promote self-renewal or tumorigenesis by CNS stem/progenitor cells. To test this we generated Nestin-Bmi-1-GFP transgenic mice. Analysis of two independent lines with expression in the fetal and adult CNS demonstrated that transgenic neural stem cells formed larger colonies, more self-renewing divisions, and more neurons in culture. However, in vivo, Bmi-1 over-expression had little effect on CNS stem cell frequency, subventricular zone proliferation, olfactory bulb neurogenesis, or neurogenesis/gliogenesis during development. Bmi-1 transgenic mice were born with enlarged lateral ventricles and a minority developed idiopathic hydrocephalus as adults, but none of the transgenic mice formed detectable CNS tumors, even when aged. The more pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16(Ink4a) and p19(Arf) in culture, proteins that are generally not expressed by neural stem/progenitor cells in young mice in vivo. Bmi-1 over-expression therefore has more pronounced effects in culture and does not appear to be sufficient to induce tumorigenesis in vivo.\n" ], "offsets": [ [ 0, 1572 ] ] } ]

[ { "id": "PMID-19389366_T2", "type": "Cell", "text": [ "neural stem/progenitor cells" ], "offsets": [ [ 25, 53 ] ], "normalized": [] }, { "id": "PMID-19389366_T4", "type": "Cell", "text": [ "stem cells" ], "offsets": [ [ 217, 227 ] ], "normalized": [] }, { "id": "PMID-19389366_T5", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 241, 248 ] ], "normalized": [] }, { "id": "PMID-19389366_T6", "type": "Anatomical_system", "text": [ "central nervous system" ], "offsets": [ [ 264, 286 ] ], "normalized": [] }, { "id": "PMID-19389366_T7", "type": "Anatomical_system", "text": [ "CNS" ], "offsets": [ [ 288, 291 ] ], "normalized": [] }, { "id": "PMID-19389366_T10", "type": "Cancer", "text": [ "gliomas" ], "offsets": [ [ 337, 344 ] ], "normalized": [] }, { "id": "PMID-19389366_T12", "type": "Cell", "text": [ "CNS stem/progenitor cells" ], "offsets": [ [ 481, 506 ] ], "normalized": [] }, { "id": "PMID-19389366_T17", "type": "Anatomical_system", "text": [ "fetal" ], "offsets": [ [ 625, 630 ] ], "normalized": [] }, { "id": "PMID-19389366_T18", "type": "Anatomical_system", "text": [ "adult CNS" ], "offsets": [ [ 635, 644 ] ], "normalized": [] }, { "id": "PMID-19389366_T19", "type": "Cell", "text": [ "neural stem cells" ], "offsets": [ [ 674, 691 ] ], "normalized": [] }, { "id": "PMID-19389366_T20", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 755, 762 ] ], "normalized": [] }, { "id": "PMID-19389366_T22", "type": "Cell", "text": [ "CNS stem cell" ], "offsets": [ [ 836, 849 ] ], "normalized": [] }, { "id": "PMID-19389366_T23", "type": "Immaterial_anatomical_entity", "text": [ "subventricular zone" ], "offsets": [ [ 861, 880 ] ], "normalized": [] }, { "id": "PMID-19389366_T24", "type": "Multi-tissue_structure", "text": [ "olfactory bulb" ], "offsets": [ [ 896, 910 ] ], "normalized": [] }, { "id": "PMID-19389366_T27", "type": "Multi-tissue_structure", "text": [ "lateral ventricles" ], "offsets": [ [ 1019, 1037 ] ], "normalized": [] }, { "id": "PMID-19389366_T29", "type": "Cancer", "text": [ "CNS tumors" ], "offsets": [ [ 1149, 1159 ] ], "normalized": [] }, { "id": "PMID-19389366_T35", "type": "Cell", "text": [ "neural stem/progenitor cells" ], "offsets": [ [ 1379, 1407 ] ], "normalized": [] }, { "id": "PMID-19389366_T1", "type": "Cell", "text": [ "colonies" ], "offsets": [ [ 706, 714 ] ], "normalized": [] } ]

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[ { "id": "PMC-2861602-sec-09__text", "type": "sec", "text": [ "Discussion\nThis is the first study to employ such a large number of replicated samples in order to assess the bacterial communities of healthy and diseased corals, and the first culture-independent assessment of bacterial communities on Acroporid WS corals on the GBR. Despite the potential of not capturing rare or very low abundance bacterial ribotypes, the DGGE analysis used in this study indicated similar results of captured bacterial ribotypes and tentative bacterial species replacement in unhealthy corals to that of less replicated studies using other non-culture based techniques (e.g. [3], [54], [69]; Figure 4). The results from this research reinforce, with statistically relevant data, that corals harbour bacterial communities different to the water column [7], [9], [42], corroborate findings that corals associate only with certain specific bacterial groups, and that these coral-associated bacterial communities are 'host' species-specific [2]. The data presented here highlight a cluster of bacterial ribotypes frequently associated with corals, and the distribution of these bacterial ribotypes on healthy and diseased corals, which allows for further targeted research into a tentative link between these common coral associates and coral health. This study indicates that coral bacterial community assessments require a number of replicates per coral species and site to accurately describe the diversity present across the population and in order to draw inferences on health-related changes in the community composition. In addition, the comparisons of healthy and diseased Acropora hyacinthus samples showed that bacterial communities can change dramatically in diseased individuals. The DGGE profiles observed for corals displaying signs of White Syndrome comprised a range of bacterial ribotypes not generally found on healthy corals, including close relatives of bacteria previously found on Black Band Diseased corals. However the community profiles across the samples taken from diseased coral colonies were inconsistent and not indicative of a single bacterial causative agent.\n\n" ], "offsets": [ [ 0, 2111 ] ] } ]

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[ { "id": "PMID-17523137__text", "type": "abstract", "text": [ "Characterization of transferrin glycoforms in human serum by CE-UV and CE-ESI-MS.\nHuman transferrin (Tf) is a model glycoprotein for congenital disorders of glycosylation (CDG) diagnosis. In the last few years, new CE-UV methods for intact Tf glycoforms analysis have been developed using nonvolatile BGEs and organic modifiers. However, the use of these BGEs does not allow the coupling of these procedures with electrospray MS (ESI-MS). In this study, a new CE-UV separation method of Tf glycoforms is developed, using a double-layer stable coating and a volatile BGE based on ammonium acetate. The separation method is optimized using standard Tf and their potential is demonstrated applying the method to the analysis of sera Tf from healthy individuals and CDG patients. The CE-UV separation method has been coupled to ESI-MS detection. Main parameters such as sheath liquid composition are optimized in order to obtain a good sensitivity. The CE-ESI-MS method has also been used in serum samples obtaining the separation of the different proteins present in serum and partial separation of Tf glycoforms. Different mass spectra and deconvoluted molecular masses were obtained for each sialoform, allowing unequivocal glycoform identification.\n" ], "offsets": [ [ 0, 1249 ] ] } ]

[ { "id": "PMID-17523137_T1", "type": "Organism_substance", "text": [ "sera" ], "offsets": [ [ 725, 729 ] ], "normalized": [] }, { "id": "PMID-17523137_T2", "type": "Organism_substance", "text": [ "serum samples" ], "offsets": [ [ 988, 1001 ] ], "normalized": [] }, { "id": "PMID-17523137_T3", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1064, 1069 ] ], "normalized": [] }, { "id": "PMID-17523137_T4", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 52, 57 ] ], "normalized": [] } ]

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[ { "id": "PMC-1698941-caption-09__text", "type": "caption", "text": [ "Comparison of the Predicted Irr Regulon and ICE Motifs with the Published Expression Microarray Data for Iron- and Irr-Affected Genes in Bradyrhizobium japonicum\n" ], "offsets": [ [ 0, 162 ] ] } ]

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[ { "id": "PMID-12419822__text", "type": "abstract", "text": [ "Identification of Dss1 as a 12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in keratinocyte progenitor cells, with possible involvement in early skin tumorigenesis. \nThis study identifies genes expressed early in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin carcinogenesis in genetically initiated Tg.AC v-Ha-ras transgenic mice. Keratinocyte progenitor cells from TPA-treated Tg.AC mice were isolated with fluorescence-activated cell sorting and expression was analyzed using cDNA microarray technology. Eleven genes were identified whose expression changed significantly in response to carcinogen treatment. Deleted in split hand/split foot 1 (Dss1) is a gene associated with a heterogeneous limb developmental disorder called split hand/split foot malformation. cDNA microarray expression analysis showed that the mouse homologue of Dss1 is induced by TPA. Dss1 overexpression was detected by Northern blot analysis in early TPA-treated hyperplastic skins and in JB6 Cl 41-5a epidermal cells. Interestingly, Dss1 expression was also shown to be elevated in skin papillomas relative to normal skins, and further increased in squamous cell malignancies. Functional studies by ectopically constitutive expression of Dss1 in JB6 Cl 41-5a preneoplastic cells strongly increased focus formation and proliferation of these cells and enhanced efficiency of neoplastic transformation of the cells in soft agar. These results strongly suggest that Dss1 is a TPA-inducible gene that may play an important role in the early stages of skin carcinogenesis.\n" ], "offsets": [ [ 0, 1572 ] ] } ]

[ { "id": "PMID-12419822_T3", "type": "Cell", "text": [ "keratinocyte progenitor cells" ], "offsets": [ [ 94, 123 ] ], "normalized": [] }, { "id": "PMID-12419822_T4", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 160, 164 ] ], "normalized": [] }, { "id": "PMID-12419822_T7", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 279, 283 ] ], "normalized": [] }, { "id": "PMID-12419822_T10", "type": "Cell", "text": [ "Keratinocyte progenitor cells" ], "offsets": [ [ 356, 385 ] ], "normalized": [] }, { "id": "PMID-12419822_T13", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 456, 460 ] ], "normalized": [] }, { "id": "PMID-12419822_T16", "type": "Organism_subdivision", "text": [ "limb" ], "offsets": [ [ 720, 724 ] ], "normalized": [] }, { "id": "PMID-12419822_T17", "type": "Organism_subdivision", "text": [ "hand" ], "offsets": [ [ 761, 765 ] ], "normalized": [] }, { "id": "PMID-12419822_T18", "type": "Organism_subdivision", "text": [ "foot" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-12419822_T24", "type": "Pathological_formation", "text": [ "hyperplastic skins" ], "offsets": [ [ 966, 984 ] ], "normalized": [] }, { "id": "PMID-12419822_T25", "type": "Cell", "text": [ "JB6 Cl 41-5a epidermal cells" ], "offsets": [ [ 992, 1020 ] ], "normalized": [] }, { "id": "PMID-12419822_T27", "type": "Organ", "text": [ "skin papillomas" ], "offsets": [ [ 1086, 1101 ] ], "normalized": [] }, { "id": "PMID-12419822_T28", "type": "Organ", "text": [ "skins" ], "offsets": [ [ 1121, 1126 ] ], "normalized": [] }, { "id": "PMID-12419822_T29", "type": "Cancer", "text": [ "squamous cell malignancies" ], "offsets": [ [ 1153, 1179 ] ], "normalized": [] }, { "id": "PMID-12419822_T31", "type": "Cell", "text": [ "JB6 Cl 41-5a preneoplastic cells" ], "offsets": [ [ 1250, 1282 ] ], "normalized": [] }, { "id": "PMID-12419822_T32", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1345, 1350 ] ], "normalized": [] }, { "id": "PMID-12419822_T33", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1411, 1416 ] ], "normalized": [] }, { "id": "PMID-12419822_T36", "type": "Organ", "text": [ "skin" ], "offsets": [ [ 1551, 1555 ] ], "normalized": [] }, { "id": "PMID-12419822_T62", "type": "Cell", "text": [ "focus" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-12419822_T1", "type": "Cancer", "text": [ "neoplastic" ], "offsets": [ [ 1378, 1388 ] ], "normalized": [] } ]

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[ { "id": "PMC-2792620-sec-33__text", "type": "sec", "text": [ "Surgery\nTrabeculectomy should be considered in all patients, when the 'target IOP' is not achieved with glaucoma medications and if the expected rate of visual loss could affect the patient during their lifetime. In this procedure, an opening is made in the trabecular meshwork, so that aqueous humor can drain into the sclera.\nMany patients can discontinue glaucoma medications after surgery. Approximately one-third of the trabeculectomy patients develop cataract within five years. If trabeculectomy fails, another type of surgery places a drainage tube (Molteno tube) in the eye, between the cornea and iris, which exits at the junction of the cornea and sclera. Cyclodestructive procedures, which lower IOP by destroying the ciliary body, are typically reserved for eyes, which are refractory to all other forms of therapy. These procedures include cyclocryotherapy, cylcodiathermy and laser cyclophotocoagulation.[91-93]\n" ], "offsets": [ [ 0, 927 ] ] } ]

[ { "id": "PMC-2792620-sec-33_T1", "type": "Organism_substance", "text": [ "aqueous humor" ], "offsets": [ [ 287, 300 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T2", "type": "Multi-tissue_structure", "text": [ "sclera" ], "offsets": [ [ 320, 326 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T3", "type": "Organ", "text": [ "eye" ], "offsets": [ [ 579, 582 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T4", "type": "Multi-tissue_structure", "text": [ "cornea" ], "offsets": [ [ 596, 602 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T5", "type": "Multi-tissue_structure", "text": [ "iris" ], "offsets": [ [ 607, 611 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T6", "type": "Multi-tissue_structure", "text": [ "cornea" ], "offsets": [ [ 648, 654 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T7", "type": "Multi-tissue_structure", "text": [ "sclera" ], "offsets": [ [ 659, 665 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T8", "type": "Multi-tissue_structure", "text": [ "ciliary body" ], "offsets": [ [ 730, 742 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T9", "type": "Organ", "text": [ "eyes" ], "offsets": [ [ 771, 775 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T10", "type": "Organ", "text": [ "trabecular" ], "offsets": [ [ 258, 268 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T11", "type": "Pathological_formation", "text": [ "glaucoma" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMC-2792620-sec-33_T12", "type": "Pathological_formation", "text": [ "glaucoma" ], "offsets": [ [ 358, 366 ] ], "normalized": [] } ]

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[ { "id": "PMID-11943784__text", "type": "abstract", "text": [ "Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. \nCancer cells display high rates of aerobic glycolysis, a phenomenon known historically as the Warburg effect. Lactate and pyruvate, the end products of glycolysis, are highly produced by cancer cells even in the presence of oxygen. Hypoxia-induced gene expression in cancer cells has been linked to malignant transformation. Here we provide evidence that lactate and pyruvate regulate hypoxia-inducible gene expression independently of hypoxia by stimulating the accumulation of hypoxia-inducible Factor 1alpha (HIF-1alpha). In human gliomas and other cancer cell lines, the accumulation of HIF-1alpha protein under aerobic conditions requires the metabolism of glucose to pyruvate that prevents the aerobic degradation of HIF-1alpha protein, activates HIF-1 DNA binding activity, and enhances the expression of several HIF-1-activated genes including erythropoietin, vascular endothelial growth factor, glucose transporter 3, and aldolase A. Our findings support a novel role for pyruvate in metabolic signaling and suggest a mechanism by which high rates of aerobic glycolysis can promote the malignant transformation and survival of cancer cells.\n" ], "offsets": [ [ 0, 1260 ] ] } ]

[ { "id": "PMID-11943784_T2", "type": "Cell", "text": [ "Cancer cells" ], "offsets": [ [ 110, 122 ] ], "normalized": [] }, { "id": "PMID-11943784_T5", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 297, 309 ] ], "normalized": [] }, { "id": "PMID-11943784_T7", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 377, 389 ] ], "normalized": [] }, { "id": "PMID-11943784_T13", "type": "Cancer", "text": [ "gliomas" ], "offsets": [ [ 644, 651 ] ], "normalized": [] }, { "id": "PMID-11943784_T14", "type": "Cell", "text": [ "cancer cell lines" ], "offsets": [ [ 662, 679 ] ], "normalized": [] }, { "id": "PMID-11943784_T27", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1246, 1258 ] ], "normalized": [] } ]

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[ { "id": "PMID-19351864__text", "type": "abstract", "text": [ "PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. \nHuman pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG overexpression in a representative ESCC cell line, EC9706, increased in vitro cell migration and invasion and promoted in vivo lymph node metastasis. Suppressing PTTG expression by siRNA decreased cell motility in both PTTG-HA/EC9706 and KYSE150 cells. By using mass spectrometric analysis, we identified that PTTG up-regulated S100A4 and galectin-1 secretion and down-regulated tissue inhibitor of metalloproteinase-2 secretion to the culture media. PTTG induced S100A4 and galectin-1 mRNA and protein expression as assessed by Western blot and reverse transcription-PCR. Attenuating galectin-1 expression by siRNA constrained PTTG-HA/EC9706 cell motility (P < 0.05). PTTG activated E-box transcription and induced c-Myc protein expression in EC9706 cells, which in turn may act on an E-box motif within the galectin-1 promoter. Chromatin immunoprecipitation assays further confirmed specific c-Myc binding to galectin-1 promoter. PTTG-induced galectin-1 transactivation and expression were mediated by c-Myc, and both inductions were suppressed by c-Myc RNAi cotranfection. These findings elucidate the molecular mechanisms of PTTG overexpression in promoting tumor metastasis, whereby up-regulated PTTG modulates expression and secretion of metastasis-related factors to facilitate cell motility.\n" ], "offsets": [ [ 0, 1793 ] ] } ]

[ { "id": "PMID-19351864_T2", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "PMID-19351864_T4", "type": "Cancer", "text": [ "esophageal squamous cell carcinoma" ], "offsets": [ [ 60, 94 ] ], "normalized": [] }, { "id": "PMID-19351864_T8", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 198, 204 ] ], "normalized": [] }, { "id": "PMID-19351864_T12", "type": "Tissue", "text": [ "primary esophageal squamous cell carcinoma (ESCC) tumor tissues" ], "offsets": [ [ 320, 383 ] ], "normalized": [] }, { "id": "PMID-19351864_T14", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 446, 456 ] ], "normalized": [] }, { "id": "PMID-19351864_T16", "type": "Cell", "text": [ "ESCC cell line" ], "offsets": [ [ 528, 542 ] ], "normalized": [] }, { "id": "PMID-19351864_T17", "type": "Cell", "text": [ "EC9706" ], "offsets": [ [ 544, 550 ] ], "normalized": [] }, { "id": "PMID-19351864_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 571, 575 ] ], "normalized": [] }, { "id": "PMID-19351864_T19", "type": "Multi-tissue_structure", "text": [ "lymph node" ], "offsets": [ [ 620, 630 ] ], "normalized": [] }, { "id": "PMID-19351864_T21", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 690, 694 ] ], "normalized": [] }, { "id": "PMID-19351864_T22", "type": "Cell", "text": [ "PTTG-HA/EC9706" ], "offsets": [ [ 712, 726 ] ], "normalized": [] }, { "id": "PMID-19351864_T24", "type": "Cell", "text": [ "KYSE150 cells" ], "offsets": [ [ 731, 744 ] ], "normalized": [] }, { "id": "PMID-19351864_T28", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 872, 878 ] ], "normalized": [] }, { "id": "PMID-19351864_T34", "type": "Cell", "text": [ "PTTG-HA/EC9706 cell" ], "offsets": [ [ 1121, 1140 ] ], "normalized": [] }, { "id": "PMID-19351864_T38", "type": "Cell", "text": [ "EC9706 cells" ], "offsets": [ [ 1237, 1249 ] ], "normalized": [] }, { "id": "PMID-19351864_T40", "type": "Cellular_component", "text": [ "Chromatin" ], "offsets": [ [ 1323, 1332 ] ], "normalized": [] }, { "id": "PMID-19351864_T48", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 1655, 1660 ] ], "normalized": [] }, { "id": "PMID-19351864_T50", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1778, 1782 ] ], "normalized": [] } ]

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[ { "id": "PMID-7504687__text", "type": "abstract", "text": [ "Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. \nTGF-beta effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-beta 1, -beta 2, and -beta 3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity. Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-beta 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical. Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-beta 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-beta in the progression of mammary carcinomas by suppressing host immune surveillance.\n" ], "offsets": [ [ 0, 1617 ] ] } ]

[ { "id": "PMID-7504687_T2", "type": "Cell", "text": [ "breast cancer cell" ], "offsets": [ [ 62, 80 ] ], "normalized": [] }, { "id": "PMID-7504687_T4", "type": "Cell", "text": [ "spleen natural killer cell" ], "offsets": [ [ 115, 141 ] ], "normalized": [] }, { "id": "PMID-7504687_T5", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 188, 198 ] ], "normalized": [] }, { "id": "PMID-7504687_T9", "type": "Cancer", "text": [ "breast cancer" ], "offsets": [ [ 235, 248 ] ], "normalized": [] }, { "id": "PMID-7504687_T11", "type": "Tissue", "text": [ "stroma" ], "offsets": [ [ 297, 303 ] ], "normalized": [] }, { "id": "PMID-7504687_T12", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 371, 376 ] ], "normalized": [] }, { "id": "PMID-7504687_T17", "type": "Cell", "text": [ "MDA-231" ], "offsets": [ [ 498, 505 ] ], "normalized": [] }, { "id": "PMID-7504687_T19", "type": "Cell", "text": [ "breast cancer cell line" ], "offsets": [ [ 512, 535 ] ], "normalized": [] }, { "id": "PMID-7504687_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 558, 563 ] ], "normalized": [] }, { "id": "PMID-7504687_T23", "type": "Cell", "text": [ "spleen natural killer (NK) cell" ], "offsets": [ [ 596, 627 ] ], "normalized": [] }, { "id": "PMID-7504687_T24", "type": "Immaterial_anatomical_entity", "text": [ "Intraperitoneal" ], "offsets": [ [ 638, 653 ] ], "normalized": [] }, { "id": "PMID-7504687_T25", "type": "Immaterial_anatomical_entity", "text": [ "intraperitoneal" ], "offsets": [ [ 691, 706 ] ], "normalized": [] }, { "id": "PMID-7504687_T26", "type": "Cell", "text": [ "tumor cells" ], "offsets": [ [ 722, 733 ] ], "normalized": [] }, { "id": "PMID-7504687_T27", "type": "Cancer", "text": [ "intraabdominal tumor" ], "offsets": [ [ 745, 765 ] ], "normalized": [] }, { "id": "PMID-7504687_T28", "type": "Cancer", "text": [ "lung metastases" ], "offsets": [ [ 770, 785 ] ], "normalized": [] }, { "id": "PMID-7504687_T30", "type": "Cancer", "text": [ "MDA-231 subcutaneous tumors" ], "offsets": [ [ 903, 930 ] ], "normalized": [] }, { "id": "PMID-7504687_T31", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 977, 983 ] ], "normalized": [] }, { "id": "PMID-7504687_T32", "type": "Immaterial_anatomical_entity", "text": [ "Intraperitoneal" ], "offsets": [ [ 1000, 1015 ] ], "normalized": [] }, { "id": "PMID-7504687_T34", "type": "Cell", "text": [ "spleen NK cell" ], "offsets": [ [ 1077, 1091 ] ], "normalized": [] }, { "id": "PMID-7504687_T35", "type": "Cancer", "text": [ "MDA-231 primary tumor" ], "offsets": [ [ 1122, 1143 ] ], "normalized": [] }, { "id": "PMID-7504687_T36", "type": "Cancer", "text": [ "metastases" ], "offsets": [ [ 1147, 1157 ] ], "normalized": [] }, { "id": "PMID-7504687_T37", "type": "Cell", "text": [ "NK cell" ], "offsets": [ [ 1190, 1197 ] ], "normalized": [] }, { "id": "PMID-7504687_T39", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1262, 1267 ] ], "normalized": [] }, { "id": "PMID-7504687_T40", "type": "Cell", "text": [ "MDA-231 cells" ], "offsets": [ [ 1297, 1310 ] ], "normalized": [] }, { "id": "PMID-7504687_T41", "type": "Cell", "text": [ "NK cell" ], "offsets": [ [ 1325, 1332 ] ], "normalized": [] }, { "id": "PMID-7504687_T43", "type": "Cell", "text": [ "blood lymphocytes" ], "offsets": [ [ 1351, 1368 ] ], "normalized": [] }, { "id": "PMID-7504687_T46", "type": "Cell", "text": [ "tumor cell" ], "offsets": [ [ 1515, 1525 ] ], "normalized": [] }, { "id": "PMID-7504687_T48", "type": "Cancer", "text": [ "mammary carcinomas" ], "offsets": [ [ 1557, 1575 ] ], "normalized": [] } ]

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[ { "id": "PMID-19509166__text", "type": "abstract", "text": [ "Fibroblast growth factor receptor 2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma.\nPURPOSE: Tumor fibroblasts (TF) have been suggested to play an essential role in the complex process of tumor-stroma interactions and tumorigenesis. The aim of the present study was to investigate the specific role of TF in the esophageal cancer microenvironment. EXPERIMENTAL DESIGN: An Affymetrix expression microarray was used to compare gene expression profiles between six pairs of TFs and normal fibroblasts from esophageal squamous cell carcinoma (ESCC). Differentially expressed genes were identified, and a subset was evaluated by quantitative real-time PCR and immunohistochemistry. RESULTS: About 43% (126 of 292) of known deregulated genes in TFs were associated with cell proliferation, extracellular matrix remodeling, and immune response. Up-regulation of fibroblast growth factor receptor 2 (FGFR2), which showed the most significant change, was detected in all six tested TFs compared with their paired normal fibroblasts. A further study found that FGFR2-positive fibroblasts were only observed inside the tumor tissues and not in tumor-surrounding stromal tissues, suggesting that FGFR2 could be used as a TF-specific marker in ESCC. Moreover, the conditioned medium from TFs was found to be able to promote ESCC tumor cell growth, migration, and invasion in vitro. CONCLUSIONS: Our study provides new candidate genes for the esophageal cancer microenvironment. Based on our results, we hypothesize that FGFR2(+)-TFs might provide cancer cells with a suitable microenvironment via secretion of proteins that could promote cancer development and progression through stimulation of cancer cell proliferation, induction of angiogenesis, inhibition of cell adhesion, enhancement of cell mobility, and promotion of the epithelial-mesenchymal transition.\n" ], "offsets": [ [ 0, 1924 ] ] } ]

[ { "id": "PMID-19509166_T1", "type": "Cell", "text": [ "Fibroblast growth factor receptor 2-positive fibroblasts" ], "offsets": [ [ 0, 56 ] ], "normalized": [] }, { "id": "PMID-19509166_T3", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 97, 102 ] ], "normalized": [] }, { "id": "PMID-19509166_T4", "type": "Cancer", "text": [ "esophageal carcinoma" ], "offsets": [ [ 134, 154 ] ], "normalized": [] }, { "id": "PMID-19509166_T5", "type": "Cell", "text": [ "Tumor fibroblasts" ], "offsets": [ [ 165, 182 ] ], "normalized": [] }, { "id": "PMID-19509166_T6", "type": "Cell", "text": [ "TF" ], "offsets": [ [ 184, 186 ] ], "normalized": [] }, { "id": "PMID-19509166_T7", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 260, 265 ] ], "normalized": [] }, { "id": "PMID-19509166_T8", "type": "Tissue", "text": [ "stroma" ], "offsets": [ [ 266, 272 ] ], "normalized": [] }, { "id": "PMID-19509166_T9", "type": "Cell", "text": [ "TF" ], "offsets": [ [ 374, 376 ] ], "normalized": [] }, { "id": "PMID-19509166_T10", "type": "Cancer", "text": [ "esophageal cancer" ], "offsets": [ [ 384, 401 ] ], "normalized": [] }, { "id": "PMID-19509166_T11", "type": "Cell", "text": [ "TFs" ], "offsets": [ [ 543, 546 ] ], "normalized": [] }, { "id": "PMID-19509166_T12", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 558, 569 ] ], "normalized": [] }, { "id": "PMID-19509166_T13", "type": "Cancer", "text": [ "esophageal squamous cell carcinoma" ], "offsets": [ [ 575, 609 ] ], "normalized": [] }, { "id": "PMID-19509166_T14", "type": "Cancer", "text": [ "ESCC" ], "offsets": [ [ 611, 615 ] ], "normalized": [] }, { "id": "PMID-19509166_T15", "type": "Cell", "text": [ "TFs" ], "offsets": [ [ 811, 814 ] ], "normalized": [] }, { "id": "PMID-19509166_T16", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 836, 840 ] ], "normalized": [] }, { "id": "PMID-19509166_T17", "type": "Cellular_component", "text": [ "extracellular matrix" ], "offsets": [ [ 856, 876 ] ], "normalized": [] }, { "id": "PMID-19509166_T20", "type": "Cell", "text": [ "TFs" ], "offsets": [ [ 1045, 1048 ] ], "normalized": [] }, { "id": "PMID-19509166_T21", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1083, 1094 ] ], "normalized": [] }, { "id": "PMID-19509166_T22", "type": "Cell", "text": [ "FGFR2-positive fibroblasts" ], "offsets": [ [ 1123, 1149 ] ], "normalized": [] }, { "id": "PMID-19509166_T24", "type": "Tissue", "text": [ "tumor tissues" ], "offsets": [ [ 1180, 1193 ] ], "normalized": [] }, { "id": "PMID-19509166_T25", "type": "Tissue", "text": [ "tumor-surrounding stromal tissues" ], "offsets": [ [ 1205, 1238 ] ], "normalized": [] }, { "id": "PMID-19509166_T27", "type": "Cell", "text": [ "TF" ], "offsets": [ [ 1281, 1283 ] ], "normalized": [] }, { "id": "PMID-19509166_T28", "type": "Cancer", "text": [ "ESCC" ], "offsets": [ [ 1303, 1307 ] ], "normalized": [] }, { "id": "PMID-19509166_T29", "type": "Cell", "text": [ "TFs" ], "offsets": [ [ 1347, 1350 ] ], "normalized": [] }, { "id": "PMID-19509166_T30", "type": "Cell", "text": [ "ESCC tumor cell" ], "offsets": [ [ 1383, 1398 ] ], "normalized": [] }, { "id": "PMID-19509166_T31", "type": "Cancer", "text": [ "esophageal cancer" ], "offsets": [ [ 1501, 1518 ] ], "normalized": [] }, { "id": "PMID-19509166_T32", "type": "Cell", "text": [ "FGFR2(+)-TFs" ], "offsets": [ [ 1579, 1591 ] ], "normalized": [] }, { "id": "PMID-19509166_T34", "type": "Cell", "text": [ "cancer cells" ], "offsets": [ [ 1606, 1618 ] ], "normalized": [] }, { "id": "PMID-19509166_T35", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 1697, 1703 ] ], "normalized": [] }, { "id": "PMID-19509166_T36", "type": "Cell", "text": [ "cancer cell" ], "offsets": [ [ 1755, 1766 ] ], "normalized": [] }, { "id": "PMID-19509166_T37", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1823, 1827 ] ], "normalized": [] }, { "id": "PMID-19509166_T38", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1853, 1857 ] ], "normalized": [] }, { "id": "PMID-19509166_T39", "type": "Cell", "text": [ "epithelial" ], "offsets": [ [ 1889, 1899 ] ], "normalized": [] }, { "id": "PMID-19509166_T40", "type": "Cell", "text": [ "mesenchymal" ], "offsets": [ [ 1900, 1911 ] ], "normalized": [] } ]

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[ { "id": "PMID-3109978__text", "type": "abstract", "text": [ "Epidermal growth factor and its receptor. \nEpidermal growth factor (EGF) binds with high affinity and specificity to a single site on the external domain of its transmembrane receptor to activate the tyrosine protein kinase activity of its cytoplasmic portion. The EGF receptor gene is amplified and over-expressed in several human tumors, suggesting that increased concentrations of the proto-oncogene leads to constitutive activity similar to that seen with oncogene erb B. Synthesis and degradation of the EGF receptor are regulated, in addition, covalent modification by phosphorylation regulates activity of the receptor protein. Intramolecular self-phosphorylation of Tyr1173 removes a competitive inhibitory constraint to enhance phosphorylation of substrates. Phosphorylation of Thr654 by protein kinase C decreases high affinity EGF binding and EGF-stimulated tyrosine protein kinase activity, providing a mechanism for heterologous regulation of the EGF receptor by tumor promoters and other ligand X receptor complexes. Extensive regulation contributes to normal growth control, abrogation of regulatory controls contributes to uncontrolled growth as seen with erb B transformation and EGF receptor gene amplification in human tumors.\n" ], "offsets": [ [ 0, 1246 ] ] } ]

[ { "id": "PMID-3109978_T4", "type": "Cellular_component", "text": [ "transmembrane" ], "offsets": [ [ 161, 174 ] ], "normalized": [] }, { "id": "PMID-3109978_T5", "type": "Organism_substance", "text": [ "cytoplasmic" ], "offsets": [ [ 240, 251 ] ], "normalized": [] }, { "id": "PMID-3109978_T8", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 332, 338 ] ], "normalized": [] }, { "id": "PMID-3109978_T17", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 976, 981 ] ], "normalized": [] }, { "id": "PMID-3109978_T22", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1238, 1244 ] ], "normalized": [] } ]

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[ { "id": "PMC-3203455-sec-04__text", "type": "sec", "text": [ "4.\nThe kinetochore\nThe arguments built in the previous section lead to the conclusion that it is essential to understand error correction and spindle checkpoint signalling in the context of the complex structural organization of the kinetochore. A complete account of kinetochore organization is beyond the scope of this review and several reviews on this topic have been made available recently [21,22]. Suffice to say that kinetochores are thought to consist of an inner plate hosting an interface between the 15-subunit constitutive centromere-associated network (CCAN) and specialized centromeric chromatin; and an outer plate containing the 10-subunit KMN network (from the initials of its Knl1, Mis12 and Ndc80 subcomplexes) implicated in microtubule binding. The CCAN and KMN networks are tightly connected. An interaction between CENP-C (CCAN) and the Mis12 complex (KMN network) provides an important point of contact [81-83]. The existence of additional points of contact, including one between CENP-T (CCAN) and the Ndc80 subcomplex (KMN network) [83,84], is supported by extensive analyses of localization dependencies of kinetochore proteins and from initial experiments of biochemical reconstitution.\nBiochemical and structural studies, including super-resolution investigations of kinetochore organization by fluorescence microscopy, have finally resulted in rather precise maps of the relative position of many structural kinetochore proteins and of several checkpoint components [85-88]. For instance, these studies clarified that the highly elongated 4-subunit Ndc80 complex, conserved in all eukaryotes, orients its approximately 60 nm long axis at a relatively small angle with the inter-kinetochore axis [85-87]. The kinetochore-binding end of the Ndc80 complex was predicted to be positioned near the Mis12 and Knl1 complexes [87,88], and this prediction was fully confirmed in experiments of biochemical reconstitution [89].\nIn prophase Drosophila melanogaster S2 cells, the C-terminal region of the Ndc80 subunit is located approximately 65 nm outward (i.e. towards the microtubule) relative to CENP-A, the histone H3 variant that marks centromeres from yeast to humans [40]. Remarkably, it was shown that this distance increases to approximately 100 nm when kinetochores experience microtubule-dependent tension at metaphase [40]. This phenomenon is now known as intra-kinetochore stretch or tension [40,90]. A major task for the future is to understand how intra-kinetochore stretch is generated when microtubules bind the kinetochore. At one extreme, intra-kinetochore stretching might be the result of a discreet conformational change in the kinetochore caused by microtubule binding [22,91]. While this is possible, it seems unlikely when considering the great structural complexity of kinetochores. Each microtubule-binding site contains six to eight copies of the approximately 30 structural kinetochore components [85]. Furthermore, in most species, kinetochores are designed to bind multiple microtubules. Plausibly, each microtubule-binding site becomes engaged at a different time. Thus, it may be more sensible to interpret intra-kinetochore stretching as a progressive, continuous distortion of the kinetochore when microtubules are added. In agreement with this idea, intermediate levels of stretching are observed when microtubule end dynamics are inhibited through addition of taxol [40].\nImportantly, intra-kinetochore stretch was shown to correlate with the status of checkpoint activation, with high stretch being correlated with checkpoint satisfaction. This idea of checkpoint control is alternative to a previous idea that tension might be monitored at the centromere, i.e. between sister kinetochores (inter-kinetochore tension) [46]. A significant theoretical limitation of the idea that the checkpoint sensor monitors tension between sister kinetochores is that it is not applicable to meiosis I, when the sisters co-orient and the homologues pair through the chiasmata. Conversely, the intra-kinetochore tension idea is also applicable to checkpoint control in meiosis I.\n" ], "offsets": [ [ 0, 4122 ] ] } ]

[ { "id": "PMC-3203455-sec-04_T1", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 7, 18 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T2", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 233, 244 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T3", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 268, 279 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T4", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 425, 437 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T5", "type": "Cellular_component", "text": [ "chromatin" ], "offsets": [ [ 601, 610 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T6", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 745, 756 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T7", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 1134, 1145 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T8", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 1296, 1307 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T9", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 1438, 1449 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T10", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 1708, 1719 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T11", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 1738, 1749 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T12", "type": "Cell", "text": [ "S2 cells" ], "offsets": [ [ 1984, 1992 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T13", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 2094, 2105 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T14", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 2283, 2295 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T15", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 2307, 2318 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T16", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2394, 2405 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T17", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2489, 2500 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T18", "type": "Cellular_component", "text": [ "microtubules" ], "offsets": [ [ 2527, 2539 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T19", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2549, 2560 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T20", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2584, 2595 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T21", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2670, 2681 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T22", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 2692, 2703 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T23", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 2815, 2827 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T24", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 2834, 2845 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T25", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 2923, 2934 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T26", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 2982, 2994 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T27", "type": "Cellular_component", "text": [ "microtubules" ], "offsets": [ [ 3025, 3037 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T28", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 3055, 3066 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T29", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 3166, 3177 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T30", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 3236, 3247 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T31", "type": "Cellular_component", "text": [ "microtubules" ], "offsets": [ [ 3253, 3265 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T32", "type": "Cellular_component", "text": [ "microtubule" ], "offsets": [ [ 3358, 3369 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T33", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 3448, 3459 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T34", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 3735, 3747 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T35", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 3755, 3766 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T36", "type": "Cellular_component", "text": [ "kinetochores" ], "offsets": [ [ 3890, 3902 ] ], "normalized": [] }, { "id": "PMC-3203455-sec-04_T37", "type": "Cellular_component", "text": [ "kinetochore" ], "offsets": [ [ 4042, 4053 ] ], "normalized": [] } ]

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[ { "id": "PMID-12154044__text", "type": "abstract", "text": [ "Inhibition of angiogenesis by the cancer chemopreventive agent conjugated linoleic acid.\nDietary conjugated linoleic acid (CLA) has been shown previously to inhibit rat mammary carcinogenesis. In addition to direct effects on mammary epithelial cells,including decreased proliferation and induction of apoptosis, CLA may exert its effects indirectly by inhibiting the differentiation of mammary stromal cells to an endothelial cell type. Specifically, CLA was found to decrease the ability of mammary stromal cells to form complex anastomosing microcapillary networks in vitro on Engelbreth-Holm-Swarm-derived reconstituted basement membrane. This suggested that CLA might inhibit angiogenesis in vivo. To test this possibility, CD2/F(1) mice were placed on synthetic diets containing 0, 1, or 2% CLA for 6 weeks, before angiogenic challenge by s.c. injection with an angiogenic gel substrate (Matrigel pellet assay). After 7 days, the pellets from animals fed the control diet were infiltrated by abundant branching networks of blood vessels with patent lumen-containing RBCs. In contrast, pellets from the CLA-fed animals contained fewer infiltrating cells, which formed limited branching cellular networks, the majority of which had collapsed lumen and no RBCs. Both levels of dietary CLA showed similar effects, with the number of RBC-containing vessels per 20x field decreased to a third of that seen in control. Dietary CLA decreased serum levels of vascular endothelial growth factor (VEGF) and whole mammary gland levels of VEGF and its receptor Flk-1. Both cis-9, trans-11 and trans-10, cis-12 CLA isomers were effective in inhibiting angiogenesis in vitro in a dose-dependent fashion. The ability of CLA to inhibit angiogenesis may contribute to its efficacy as a chemopreventive agent.\n" ], "offsets": [ [ 0, 1797 ] ] } ]

[ { "id": "PMID-12154044_T1", "type": "Cancer", "text": [ "cancer" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "PMID-12154044_T6", "type": "Organ", "text": [ "mammary" ], "offsets": [ [ 169, 176 ] ], "normalized": [] }, { "id": "PMID-12154044_T7", "type": "Cell", "text": [ "mammary epithelial cells" ], "offsets": [ [ 226, 250 ] ], "normalized": [] }, { "id": "PMID-12154044_T9", "type": "Cell", "text": [ "mammary stromal cells" ], "offsets": [ [ 387, 408 ] ], "normalized": [] }, { "id": "PMID-12154044_T10", "type": "Cell", "text": [ "endothelial cell type" ], "offsets": [ [ 415, 436 ] ], "normalized": [] }, { "id": "PMID-12154044_T12", "type": "Cell", "text": [ "mammary stromal cells" ], "offsets": [ [ 493, 514 ] ], "normalized": [] }, { "id": "PMID-12154044_T13", "type": "Multi-tissue_structure", "text": [ "microcapillary networks" ], "offsets": [ [ 544, 567 ] ], "normalized": [] }, { "id": "PMID-12154044_T14", "type": "Cellular_component", "text": [ "basement membrane" ], "offsets": [ [ 624, 641 ] ], "normalized": [] }, { "id": "PMID-12154044_T18", "type": "Multi-tissue_structure", "text": [ "networks of blood vessels" ], "offsets": [ [ 1017, 1042 ] ], "normalized": [] }, { "id": "PMID-12154044_T19", "type": "Immaterial_anatomical_entity", "text": [ "lumen" ], "offsets": [ [ 1055, 1060 ] ], "normalized": [] }, { "id": "PMID-12154044_T20", "type": "Cell", "text": [ "RBCs" ], "offsets": [ [ 1072, 1076 ] ], "normalized": [] }, { "id": "PMID-12154044_T22", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1153, 1158 ] ], "normalized": [] }, { "id": "PMID-12154044_T23", "type": "Multi-tissue_structure", "text": [ "cellular networks" ], "offsets": [ [ 1191, 1208 ] ], "normalized": [] }, { "id": "PMID-12154044_T24", "type": "Immaterial_anatomical_entity", "text": [ "lumen" ], "offsets": [ [ 1246, 1251 ] ], "normalized": [] }, { "id": "PMID-12154044_T25", "type": "Cell", "text": [ "RBCs" ], "offsets": [ [ 1259, 1263 ] ], "normalized": [] }, { "id": "PMID-12154044_T27", "type": "Cell", "text": [ "RBC" ], "offsets": [ [ 1335, 1338 ] ], "normalized": [] }, { "id": "PMID-12154044_T28", "type": "Multi-tissue_structure", "text": [ "vessels" ], "offsets": [ [ 1350, 1357 ] ], "normalized": [] }, { "id": "PMID-12154044_T30", "type": "Organism_substance", "text": [ "serum" ], "offsets": [ [ 1440, 1445 ] ], "normalized": [] }, { "id": "PMID-12154044_T33", "type": "Organ", "text": [ "mammary gland" ], "offsets": [ [ 1508, 1521 ] ], "normalized": [] } ]

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[ { "id": "PMID-2028342__text", "type": "abstract", "text": [ "Posterior stabilization of the cervical spine with hook plates.\nHook-plate fixation is designed for posterior cervical stabilization from C2 to C7. Indications remain the same as for standard posterior fixations. The prime indications are discoligamentous injuries. The plates are hooked under the lower laminas and attached to the articular masses of the upper vertebra by oblique screws. An H-graft is placed between the spinous processes. The vertebrae are compressed together by the plates at three points, the facet joints, and graft. The resulting pre-stressed system is stable in all directions. A protocol for safe reduction of cervical dislocations is observed. Of 70 patients treated from 1979 to 1986, 51 were examined 12-54 months after surgery. All fusions consolidated. Two neurologic complications not attributable to the fixation occurred. Other major complications were not seen.\n" ], "offsets": [ [ 0, 897 ] ] } ]

[ { "id": "PMID-2028342_T1", "type": "Organism_subdivision", "text": [ "cervical spine" ], "offsets": [ [ 31, 45 ] ], "normalized": [] }, { "id": "PMID-2028342_T2", "type": "Multi-tissue_structure", "text": [ "lower laminas" ], "offsets": [ [ 298, 311 ] ], "normalized": [] }, { "id": "PMID-2028342_T3", "type": "Organ", "text": [ "vertebra" ], "offsets": [ [ 362, 370 ] ], "normalized": [] }, { "id": "PMID-2028342_T4", "type": "Organ", "text": [ "vertebrae" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "PMID-2028342_T5", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 636, 644 ] ], "normalized": [] }, { "id": "PMID-2028342_T6", "type": "Organism_subdivision", "text": [ "cervical" ], "offsets": [ [ 110, 118 ] ], "normalized": [] }, { "id": "PMID-2028342_T7", "type": "Multi-tissue_structure", "text": [ "articular masses" ], "offsets": [ [ 332, 348 ] ], "normalized": [] }, { "id": "PMID-2028342_T8", "type": "Anatomical_system", "text": [ "neurologic" ], "offsets": [ [ 788, 798 ] ], "normalized": [] } ]

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[ { "id": "PMC-2885393-caption-01__text", "type": "caption", "text": [ "Comparison of the molecular organisation of the tra-2 of A. obliqua (A), C. capitata (B) and D. melanogaster (C) and their proteins. Exons (boxes) and introns (dashed lines) are not drawn to scale. The numbers inside the boxes indicate the number of the exon. The beginning and the end of the ORF are indicated by ATG and TAA respectively. AAA stands for poly-A(+). (D) Expression of gene tra-2 of A. obliqua. RT-PCR analyses of total RNA from ovaries (O), embryos (E), from male and female larvae (L), male soma (head plus thorax, MS) and female soma (head plus thorax, FS). (E) Expression of gene tra-2 of A. obliqua. RT-PCR analysis of total RNA from A. obliqua testis. Lane 1 corresponds to PCR with primers PM1 and P2; lane 2 corresponds to PCR with primers P1 and P2 (see location of primers in Figure 1A). (F) Southern-blot corresponding to the gel shown in (E) and hybridisation with a probe specific for intron 3 of A. obliqua. The arrow marks the hybridisation to the higher band in lane 1 of Figure 1E. The size of the mRNAs encoding the proteins shown in this figure are: 1923 bp for A. obliqua mRNA, 1113 bp for C. capitata mRNA, and 960, 1583 and 1391 bp for D. melanogaster mRNAs tra2-179, tra2-226 and tra2-264, respectively.\n" ], "offsets": [ [ 0, 1242 ] ] } ]

[ { "id": "PMC-2885393-caption-01_T1", "type": "Organ", "text": [ "ovaries" ], "offsets": [ [ 444, 451 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T2", "type": "Developing_anatomical_structure", "text": [ "embryos" ], "offsets": [ [ 457, 464 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T3", "type": "Cell", "text": [ "soma" ], "offsets": [ [ 508, 512 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T4", "type": "Cell", "text": [ "soma" ], "offsets": [ [ 547, 551 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T5", "type": "Organism_subdivision", "text": [ "head" ], "offsets": [ [ 514, 518 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T6", "type": "Organism_subdivision", "text": [ "thorax" ], "offsets": [ [ 524, 530 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T7", "type": "Organism_subdivision", "text": [ "head" ], "offsets": [ [ 553, 557 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T8", "type": "Organism_subdivision", "text": [ "thorax" ], "offsets": [ [ 563, 569 ] ], "normalized": [] }, { "id": "PMC-2885393-caption-01_T9", "type": "Organ", "text": [ "testis" ], "offsets": [ [ 665, 671 ] ], "normalized": [] } ]

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[ { "id": "PMC-1828719-sec-06__text", "type": "sec", "text": [ "Mass casualty estimation on a geographic basis\nThe Defense Threat Reduction Agency (DTRA) has expended considerable effort to develop models for calculating mass casualties from a nuclear detonation. In order to specifically evaluate urban medical systems vulnerability we are employing the PC based Consequence Assessment Tool Set (CATS) v6, with ESRI's ArcGIS9 [14], CATS/JACE (Joint Assessment of Catastrophic Events) v5 with ESRI's ArcView 3.3, Hazard Prediction and Assessment Capability (HPAC) V4.04SP3 [15], as well as custom GIS and database software applications. HPAC does excellent Chemical Biological and Nuclear (CBN) modeling, although output could provide more flexibility. Additionally, results can be exported to CATS for further analysis and display. All three programs can access the current weather data from both classified and unclassified weather servers. Examples of uses of CATS/HPAC are hurricane, tidal surge and earthquake damage, prediction of the results from nuclear, biological and chemical releases, assessment of persons and infrastructure affected and at risk (e.g. which hospitals and pharmacies are under a CBN plume and are thus out of commission), and mobilization of surviving and nearby infrastructure outside the plume that would be needed to address healthcare and other emergency response needs of the community.\nThese models have been, and continue to be, developed with a view to better estimating the impact of WMD weapons in an offensive setting. However, recent DTRA enhancements and our modifications have facilitated their use in helping estimate potential casualties from a WMD terrorist incident. One area of intense interest, and somewhat of a vacuum in public health planning, has been the utility of this approach in estimating medical care vulnerabilities in such an attack, and for the calculation of the distribution of surviving medical care resources. While much work has already occurred in estimating the impact of chemical weapons (due to the dual use in chemical spill management from transportation and industrial accidents), or in nuclear power plant accident management, much less research and development has gone into estimating the impact on our civilian population of a nuclear weapon detonation from a terrorist incident in a large urban area. The models already calculate such factors as the impact of blast, thermal effects and fallout, but results are often not available at the detail level needed for civil defense purposes, casualty management, and planning the use of scarce health resources in response to a nuclear weapon detonation. Furthermore, the models do not readily facilitate the calculation of injuries from multiple effects such as burns and blast with fallout or prompt radiation. The complexity of the urban three-dimensional landscape and its local impact on thermal, blast and radiation is also poorly understood. Additionally, given their traditional world-wide focus, and the increased sensitivity to providing information on the U.S.A. of use to terrorists, the models do not provide detailed or current data that exists for the United States that would help provide better casualty estimates and response. The models can be customized locally and data updated if the user has sufficient expertise. However, there is often a significant duplication of effort due to overlapping jurisdictions and the lack of data sharing due to security and other considerations.\nCATS and HPAC are also useful for creating realistic scenarios for training and planning before a disaster strikes, thus enabling responders to drill and exercise so they know roughly what to expect and how to react. Contingency plans can be created using comprehensive national and more detailed population and infrastructure data. Should disaster strike, the affected population and the impact on critical facilities can be quickly assessed, although efforts frequently need to be expended to ensure regional and local databases are current and useful.\n" ], "offsets": [ [ 0, 4017 ] ] } ]

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[ { "id": "PMID-19082449__text", "type": "abstract", "text": [ "Clinical significance of chicken ovalbumin upstream promoter-transcription factor II expression in human colorectal cancer.\nChicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an essential role in angiogenesis and development. A previous study showed that the expression of COUP-TFII enhanced invasiveness of human lung carcinoma cells. However, no published data are available concerning the biological and clinical significance of COUP-TFII expression in colorectal cancer. Thus, our objective was to explore the expression of COUP-TFII in colorectal cancer as well as its association with clinicopathological features, and to evaluate the role of COUP-TFII as a prognostic indicator in colorectal cancer. We investigated the presence of COUP-TFII in human colorectal cancer tissues and adjacent normal tissues from 95 primary colorectal cancer patients by immunohistochemistry. The correlation between the expression of COUP-TFII and clinicopathologic features was investigated. The 3-year disease-free survival (DFS) and overall survival (OS) of patients with tumors expressing different levels of COUP-TFII were evaluated by the Kaplan-Meier method. No significant correlation was found between COUP-TFII expression and age at surgery, gender, histopathologic differentiation, vessel invasion, carcinoembryonic antigen (CEA), or nodal involvement. However, survival analysis showed that the COUP-TFII-positive group had a significantly better OS compared to COUP-TFII-negative group (80.4% vs. 57.7%, P=0.0491). Based on our results, COUP-TFII may represent a biomarker for good prognosis in colorectal cancer.\n" ], "offsets": [ [ 0, 1642 ] ] } ]

[ { "id": "PMID-19082449_T3", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 105, 122 ] ], "normalized": [] }, { "id": "PMID-19082449_T8", "type": "Cell", "text": [ "lung carcinoma cells" ], "offsets": [ [ 341, 361 ] ], "normalized": [] }, { "id": "PMID-19082449_T10", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 483, 500 ] ], "normalized": [] }, { "id": "PMID-19082449_T12", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 568, 585 ] ], "normalized": [] }, { "id": "PMID-19082449_T14", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 715, 732 ] ], "normalized": [] }, { "id": "PMID-19082449_T17", "type": "Tissue", "text": [ "colorectal cancer tissues" ], "offsets": [ [ 785, 810 ] ], "normalized": [] }, { "id": "PMID-19082449_T18", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 831, 838 ] ], "normalized": [] }, { "id": "PMID-19082449_T19", "type": "Cancer", "text": [ "primary colorectal cancer" ], "offsets": [ [ 847, 872 ] ], "normalized": [] }, { "id": "PMID-19082449_T23", "type": "Cancer", "text": [ "tumors" ], "offsets": [ [ 1090, 1096 ] ], "normalized": [] }, { "id": "PMID-19082449_T26", "type": "Multi-tissue_structure", "text": [ "vessel" ], "offsets": [ [ 1308, 1314 ] ], "normalized": [] }, { "id": "PMID-19082449_T32", "type": "Cancer", "text": [ "colorectal cancer" ], "offsets": [ [ 1623, 1640 ] ], "normalized": [] }, { "id": "PMID-19082449_T49", "type": "Multi-tissue_structure", "text": [ "nodal" ], "offsets": [ [ 1360, 1365 ] ], "normalized": [] } ]

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[ { "id": "PMID-9663607__text", "type": "abstract", "text": [ "SV40 Tag transformation of the normal invasive trophoblast results in a premalignant phenotype. I. Mechanisms responsible for hyperinvasiveness and resistance to anti-invasive action of TGFbeta. \nInvasion of the uterus by first trimester human placental extravillous trophoblast (EVT) cells depends on mechanisms shared by malignant cells. However, unlike tumor invasion, trophoblast invasion of the uterus is stringently controlled in situ by local molecules such as transforming growth factor (TGF)beta. Since EVT cells possess active invasion-associated genes but are nontumorigenic, our objective was to induce premalignant and then malignant phenotype into a normal EVT cell line in order to identify the molecular basis of tumor progression. Simian virus 40 large T antigen (SV40 Tag) was introduced into a normal human first trimester invasive EVT cell line, HTR8, established in our laboratory. Since the HTR8 line has a limited in vitro lifespan of 12-15 passages, SV40 Tag-transformed cells were selected on the basis of extended lifespan. A long-lived line, RSVT-2, was produced and an immortalized subclone, RSVT2/C, was further derived under a forced crisis regimen. We examined transformation-induced alterations in proliferative and invasive abilities, responses to the invasion and proliferation-regulating growth factor TGFbeta and changes in gene expression for invasion-associated enzymes or enzyme inhibitors. RSVT-2 and RSVT2/C cell lines were hyperproliferative and hyperinvasive when compared with the parental HTR8 cell line. They were also variably resistant to the anti-proliferative and anti-invasive signals from TGFbeta. Since both cell lines remained non-tumorigenic in nude mice, these properties indicate that they attained a premalignant phenotype. Both cell lines showed reduced expression of tissue inhibitor of metalloproteases (TIMP)-1, while TIMP-2 and plasminogen activator inhibitor (PAI)-I expression was was also reduced in RSVT2/C cells, thus contributing to their hyperinvasiveness. Their resistance to the anti-invasive action of TGFbeta was explained by the failure of TGFbeta to upregulate TIMPs and PAI-I, in contrast to the TGFbeta-induced upregulation noted in parental HTR8 cells.\n" ], "offsets": [ [ 0, 2232 ] ] } ]

[ { "id": "PMID-9663607_T3", "type": "Cell", "text": [ "trophoblast" ], "offsets": [ [ 47, 58 ] ], "normalized": [] }, { "id": "PMID-9663607_T5", "type": "Organ", "text": [ "uterus" ], "offsets": [ [ 212, 218 ] ], "normalized": [] }, { "id": "PMID-9663607_T7", "type": "Cell", "text": [ "placental extravillous trophoblast (EVT) cells" ], "offsets": [ [ 244, 290 ] ], "normalized": [] }, { "id": "PMID-9663607_T8", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 323, 338 ] ], "normalized": [] }, { "id": "PMID-9663607_T9", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 356, 361 ] ], "normalized": [] }, { "id": "PMID-9663607_T10", "type": "Cell", "text": [ "trophoblast" ], "offsets": [ [ 372, 383 ] ], "normalized": [] }, { "id": "PMID-9663607_T11", "type": "Organ", "text": [ "uterus" ], "offsets": [ [ 400, 406 ] ], "normalized": [] }, { "id": "PMID-9663607_T13", "type": "Cell", "text": [ "EVT cells" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "PMID-9663607_T14", "type": "Cell", "text": [ "EVT cell line" ], "offsets": [ [ 671, 684 ] ], "normalized": [] }, { "id": "PMID-9663607_T15", "type": "Cancer", "text": [ "tumor" ], "offsets": [ [ 729, 734 ] ], "normalized": [] }, { "id": "PMID-9663607_T21", "type": "Cell", "text": [ "EVT cell line" ], "offsets": [ [ 851, 864 ] ], "normalized": [] }, { "id": "PMID-9663607_T22", "type": "Cell", "text": [ "HTR8" ], "offsets": [ [ 866, 870 ] ], "normalized": [] }, { "id": "PMID-9663607_T23", "type": "Cell", "text": [ "HTR8 line" ], "offsets": [ [ 913, 922 ] ], "normalized": [] }, { "id": "PMID-9663607_T26", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 995, 1000 ] ], "normalized": [] }, { "id": "PMID-9663607_T27", "type": "Cell", "text": [ "line" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [] }, { "id": "PMID-9663607_T28", "type": "Cell", "text": [ "RSVT-2" ], "offsets": [ [ 1069, 1075 ] ], "normalized": [] }, { "id": "PMID-9663607_T29", "type": "Cell", "text": [ "RSVT2/C" ], "offsets": [ [ 1120, 1127 ] ], "normalized": [] }, { "id": "PMID-9663607_T31", "type": "Cell", "text": [ "RSVT-2" ], "offsets": [ [ 1430, 1436 ] ], "normalized": [] }, { "id": "PMID-9663607_T32", "type": "Cell", "text": [ "RSVT2/C cell lines" ], "offsets": [ [ 1441, 1459 ] ], "normalized": [] }, { "id": "PMID-9663607_T33", "type": "Cell", "text": [ "HTR8 cell line" ], "offsets": [ [ 1534, 1548 ] ], "normalized": [] }, { "id": "PMID-9663607_T35", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "PMID-9663607_T37", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1787, 1797 ] ], "normalized": [] }, { "id": "PMID-9663607_T41", "type": "Cell", "text": [ "RSVT2/C cells" ], "offsets": [ [ 1966, 1979 ] ], "normalized": [] }, { "id": "PMID-9663607_T47", "type": "Cell", "text": [ "HTR8 cells" ], "offsets": [ [ 2220, 2230 ] ], "normalized": [] }, { "id": "PMID-9663607_T1", "type": "Cell", "text": [ "subclone" ], "offsets": [ [ 1110, 1118 ] ], "normalized": [] } ]

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[ { "id": "PMID-2992384__text", "type": "abstract", "text": [ "On the mechanism of glycolysis stimulation by neutral detergents in 3T3 and Ehrlich ascites tumor cells. \nGlycolysis of 3T3 and Ehrlich ascites tumor cells was greatly enhanced by Nonidet P-40 or Triton X-100 at about 100 micrograms/mg cell protein. This enhanced glycolysis was partly sensitive to rutamycin and partly sensitive to ouabain, suggesting that the detergent released the control of the ATPase of the mitochondria and of the plasma membrane Na+K+-ATPase. Nonidet P-40 had no effect on glycolysis in cell-free extracts from Ehrlich ascites tumor cells to which soluble mitochondrial ATPase was added. Measuring ouabain-sensitive 22Na efflux and using ouabain-sensitive lactate production as a measure of ATP hydrolysis by the Na+K+ pump, it was shown that Nonidet P-40 greatly decreased the efficiency of the Na+K+ pump. Quercetin increased the efficiency of pumping in EAT cells both in the absence and presence of the detergent.\n" ], "offsets": [ [ 0, 943 ] ] } ]

[ { "id": "PMID-2992384_T1", "type": "Cell", "text": [ "3T3" ], "offsets": [ [ 68, 71 ] ], "normalized": [] }, { "id": "PMID-2992384_T2", "type": "Cell", "text": [ "Ehrlich ascites tumor cells" ], "offsets": [ [ 76, 103 ] ], "normalized": [] }, { "id": "PMID-2992384_T3", "type": "Cell", "text": [ "3T3" ], "offsets": [ [ 120, 123 ] ], "normalized": [] }, { "id": "PMID-2992384_T4", "type": "Cell", "text": [ "Ehrlich ascites tumor cells" ], "offsets": [ [ 128, 155 ] ], "normalized": [] }, { "id": "PMID-2992384_T7", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 236, 240 ] ], "normalized": [] }, { "id": "PMID-2992384_T11", "type": "Cellular_component", "text": [ "mitochondria" ], "offsets": [ [ 414, 426 ] ], "normalized": [] }, { "id": "PMID-2992384_T12", "type": "Cellular_component", "text": [ "plasma membrane" ], "offsets": [ [ 438, 453 ] ], "normalized": [] }, { "id": "PMID-2992384_T15", "type": "Organism_substance", "text": [ "extracts" ], "offsets": [ [ 522, 530 ] ], "normalized": [] }, { "id": "PMID-2992384_T16", "type": "Cell", "text": [ "Ehrlich ascites tumor cells" ], "offsets": [ [ 536, 563 ] ], "normalized": [] }, { "id": "PMID-2992384_T17", "type": "Cellular_component", "text": [ "mitochondrial" ], "offsets": [ [ 581, 594 ] ], "normalized": [] }, { "id": "PMID-2992384_T27", "type": "Cell", "text": [ "EAT cells" ], "offsets": [ [ 882, 891 ] ], "normalized": [] }, { "id": "PMID-2992384_T46", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 512, 516 ] ], "normalized": [] } ]

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[ { "id": "PMID-20157600__text", "type": "abstract", "text": [ "Further Characterization of Activin A-induced IgA Response in Murine B Lymphocytes.\nWe have recently shown that activin A, a member of TGF-beta superfamily, stimulates mouse B cells to express IgA isotype but other isotypes. In the present study, we further characterized effects of activin A on B cell growth and IgA expression. We found that activin A did not have effect on LPS-stimulated cell viability. In parallel, CFSE staining analysis revealed that activin A did not alter cell division. An increase of IgA secretion by activin A was completely abrogated by anti-activin A Ab but not by anti-TGFbeta1 Ab. In the same conditions, no other isotypes are significantly affected by each antibody treatment. Finally, activin A, as similar to TGF-beta1, increased IgA secretion by mesenteric lymph node cells. These results suggest that activin A can specifically stimulate IgA response, independent of TGF-beta in the gut.\n" ], "offsets": [ [ 0, 926 ] ] } ]

[ { "id": "PMID-20157600_T1", "type": "Cell", "text": [ "B Lymphocytes" ], "offsets": [ [ 69, 82 ] ], "normalized": [] }, { "id": "PMID-20157600_T2", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 174, 181 ] ], "normalized": [] }, { "id": "PMID-20157600_T3", "type": "Cell", "text": [ "B cell" ], "offsets": [ [ 296, 302 ] ], "normalized": [] }, { "id": "PMID-20157600_T4", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 392, 396 ] ], "normalized": [] }, { "id": "PMID-20157600_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 482, 486 ] ], "normalized": [] }, { "id": "PMID-20157600_T6", "type": "Cell", "text": [ "lymph node cells" ], "offsets": [ [ 794, 810 ] ], "normalized": [] }, { "id": "PMID-20157600_T7", "type": "Organism_subdivision", "text": [ "gut" ], "offsets": [ [ 921, 924 ] ], "normalized": [] } ]

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[ { "id": "PMC-3266646-sec-09__text", "type": "sec", "text": [ "Origins of Acquired Antibiotic Resistance Mechanisms\nRecently, D'Costa et al. (2011) have reported a metagenomic analysis of the Beringian permafrost, which is 30,000 years old. They showed molecular evidences of the ancient origins of antibiotic resistances, detecting beta-lactamases genes, vanX-like, component of the vancomycin resistance operon, and tetM, coding for a protein protecting the ribosomal target from tetracycline. Sequence analysis revealed that the beta-lactamases genes recovered from the permafrost demonstrated an amino-acid homology (53-84%) to known beta-lactamases from beta-lactams producing Streptomyces. The tetM sequences revealed a high similarity to the genes coding for the ribosomal protection protein of actinomycetes. The vanX sequence showed a similarity to the vanX gene recovered in pathogenic vancomycin resistant enterococci (VRE) and to the vanX gene from Amycolatopsis orientalis. This environmental species, belonging to the actinobacteria phylum, is a natural producer of vancomycin, and very likely the progenitor of the van genes operons, responsible for resistance to vancomycin. The integration of the van operons on transposons and on conjugative plasmids has enhanced their spread (Courvalin, 2006). Reports of VRE in freshwater have been provided by several authors (Talebi et al., 2008; Lata et al., 2009; Luczkiewicz et al., 2010). Interestingly, Schwartz et al. (2003) detected vanA genes in the biofilm of drinking water supplies, in the absence of enterococci, demonstrating the lateral transfer of this gene. Notably, the progenitors of these resistance genes are soil bacteria thus most likely, a shuttle has been responsible for the introduction of these genes into the commensal bacterial community and afterward into the pathogenic species.\n\n" ], "offsets": [ [ 0, 1804 ] ] } ]

[ { "id": "PMC-3266646-sec-09_T1", "type": "Cellular_component", "text": [ "ribosomal" ], "offsets": [ [ 397, 406 ] ], "normalized": [] }, { "id": "PMC-3266646-sec-09_T2", "type": "Cellular_component", "text": [ "ribosomal" ], "offsets": [ [ 707, 716 ] ], "normalized": [] }, { "id": "PMC-3266646-sec-09_T3", "type": "Cellular_component", "text": [ "conjugative plasmids" ], "offsets": [ [ 1185, 1205 ] ], "normalized": [] }, { "id": "PMC-3266646-sec-09_T5", "type": "Cell", "text": [ "biofilm" ], "offsets": [ [ 1451, 1458 ] ], "normalized": [] }, { "id": "PMC-3266646-sec-09_T4", "type": "Cell", "text": [ "community" ], "offsets": [ [ 1750, 1759 ] ], "normalized": [] } ]

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