id
stringlengths 1
3
| document_id
stringlengths 11
13
| passages
list | entities
list | events
list | coreferences
list | relations
list |
|---|---|---|---|---|---|---|
0 | PMID-12484699 | [
{
"id": "PMID-12484699__text",
"type": "abstract",
"text": [
"Regulation of transforming growth factor-beta signaling and vascular diseases.\n\nPURPOSE: Members of the transforming growth factor (TGF)-beta superfamily play critical roles in regulation of various cellular functions. Dysregulation of the signaling mechanisms of the TGF-beta superfamily proteins is associated with clinical diseases such as cancer, fibrotic diseases, and vascular disorders. Therefore, understanding these signaling mechanisms may provide us with novel ways to develop strategies for treating clinical diseases induced by these cytokines. METHODS: This review discusses our current understanding of the mechanisms of TGF-beta signaling, focusing on the roles of TGF-beta in regulation of vascular wall cells and on the regulation of TGF-beta superfamily signals by inhibitory Smads.\n"
],
"offsets": [
[
0,
802
]
]
}
] | [
{
"id": "PMID-12484699_T2",
"type": "Gene_or_gene_product",
"text": [
"transforming growth factor-beta"
],
"offsets": [
[
14,
45
]
],
"normalized": []
},
{
"id": "PMID-12484699_T5",
"type": "Gene_or_gene_product",
"text": [
"transforming growth factor (TGF)-beta"
],
"offsets": [
[
104,
141
]
],
"normalized": []
},
{
"id": "PMID-12484699_T8",
"type": "Gene_or_gene_product",
"text": [
"TGF-beta"
],
"offsets": [
[
268,
276
]
],
"normalized": []
},
{
"id": "PMID-12484699_T12",
"type": "Gene_or_gene_product",
"text": [
"TGF-beta"
],
"offsets": [
[
636,
644
]
],
"normalized": []
},
{
"id": "PMID-12484699_T14",
"type": "Gene_or_gene_product",
"text": [
"TGF-beta"
],
"offsets": [
[
681,
689
]
],
"normalized": []
},
{
"id": "PMID-12484699_T17",
"type": "Cell",
"text": [
"vascular wall cells"
],
"offsets": [
[
707,
726
]
],
"normalized": []
},
{
"id": "PMID-12484699_T21",
"type": "Gene_or_gene_product",
"text": [
"TGF-beta"
],
"offsets": [
[
752,
760
]
],
"normalized": []
},
{
"id": "PMID-12484699_T22",
"type": "Gene_or_gene_product",
"text": [
"Smads"
],
"offsets": [
[
795,
800
]
],
"normalized": []
}
] | [
{
"id": "PMID-12484699_E16",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
693,
703
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12484699_T17"
}
]
},
{
"id": "PMID-12484699_E19",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
738,
748
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12484699_T21"
},
{
"role": "Cause",
"ref_id": "PMID-12484699_E4"
}
]
},
{
"id": "PMID-12484699_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12484699_E5"
}
]
},
{
"id": "PMID-12484699_E2",
"type": "Regulation",
"trigger": {
"text": [
"Dysregulation"
],
"offsets": [
[
219,
232
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12484699_T8"
}
]
},
{
"id": "PMID-12484699_E3",
"type": "Regulation",
"trigger": {
"text": [
"roles"
],
"offsets": [
[
672,
677
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12484699_T14"
},
{
"role": "Theme",
"ref_id": "PMID-12484699_E16"
}
]
},
{
"id": "PMID-12484699_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory"
],
"offsets": [
[
784,
794
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12484699_T22"
}
]
},
{
"id": "PMID-12484699_E5",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
46,
55
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-12484699_T2"
}
]
},
{
"id": "PMID-12484699_E6",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
645,
654
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-12484699_T12"
}
]
}
] | [] | [] |
1 | PMID-16268479 | [
{
"id": "PMID-16268479__text",
"type": "abstract",
"text": [
"Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.\n\nDomain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.\n"
],
"offsets": [
[
0,
1759
]
]
}
] | [
{
"id": "PMID-16268479_T2",
"type": "Gene_or_gene_product",
"text": [
"high molecular weight kininogen"
],
"offsets": [
[
20,
51
]
],
"normalized": []
},
{
"id": "PMID-16268479_T6",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
61,
77
]
],
"normalized": []
},
{
"id": "PMID-16268479_T7",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
96,
99
]
],
"normalized": []
},
{
"id": "PMID-16268479_T11",
"type": "Gene_or_gene_product",
"text": [
"high molecular weight kininogen"
],
"offsets": [
[
127,
158
]
],
"normalized": []
},
{
"id": "PMID-16268479_T12",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
160,
163
]
],
"normalized": []
},
{
"id": "PMID-16268479_T17",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
199,
215
]
],
"normalized": []
},
{
"id": "PMID-16268479_T19",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
280,
283
]
],
"normalized": []
},
{
"id": "PMID-16268479_T24",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
305,
321
]
],
"normalized": []
},
{
"id": "PMID-16268479_T25",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
398,
401
]
],
"normalized": []
},
{
"id": "PMID-16268479_T31",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
449,
465
]
],
"normalized": []
},
{
"id": "PMID-16268479_T32",
"type": "Gene_or_gene_product",
"text": [
"sphingosine 1-phosphate"
],
"offsets": [
[
477,
500
]
],
"normalized": []
},
{
"id": "PMID-16268479_T33",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
502,
505
]
],
"normalized": []
},
{
"id": "PMID-16268479_T34",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
511,
545
]
],
"normalized": []
},
{
"id": "PMID-16268479_T35",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
547,
551
]
],
"normalized": []
},
{
"id": "PMID-16268479_T37",
"type": "Gene_or_gene_product",
"text": [
"P13-kinase"
],
"offsets": [
[
575,
585
]
],
"normalized": []
},
{
"id": "PMID-16268479_T38",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
586,
589
]
],
"normalized": []
},
{
"id": "PMID-16268479_T39",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
609,
612
]
],
"normalized": []
},
{
"id": "PMID-16268479_T44",
"type": "Cell",
"text": [
"pulmonary artery endothelial cell"
],
"offsets": [
[
635,
668
]
],
"normalized": []
},
{
"id": "PMID-16268479_T46",
"type": "Cell",
"text": [
"BPAE"
],
"offsets": [
[
670,
674
]
],
"normalized": []
},
{
"id": "PMID-16268479_T49",
"type": "Cell",
"text": [
"umbilical vein endothelial cell"
],
"offsets": [
[
685,
716
]
],
"normalized": []
},
{
"id": "PMID-16268479_T51",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
773,
777
]
],
"normalized": []
},
{
"id": "PMID-16268479_T52",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
781,
784
]
],
"normalized": []
},
{
"id": "PMID-16268479_T53",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
817,
820
]
],
"normalized": []
},
{
"id": "PMID-16268479_T56",
"type": "Gene_or_gene_product",
"text": [
"urokinase-type plasminogen activator receptor"
],
"offsets": [
[
850,
895
]
],
"normalized": []
},
{
"id": "PMID-16268479_T57",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
902,
905
]
],
"normalized": []
},
{
"id": "PMID-16268479_T62",
"type": "Cell",
"text": [
"BPAE cell"
],
"offsets": [
[
935,
944
]
],
"normalized": []
},
{
"id": "PMID-16268479_T66",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
1034,
1037
]
],
"normalized": []
},
{
"id": "PMID-16268479_T67",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1041,
1045
]
],
"normalized": []
},
{
"id": "PMID-16268479_T68",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
1047,
1050
]
],
"normalized": []
},
{
"id": "PMID-16268479_T71",
"type": "Gene_or_gene_product",
"text": [
"paxillin"
],
"offsets": [
[
1085,
1093
]
],
"normalized": []
},
{
"id": "PMID-16268479_T73",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
1123,
1126
]
],
"normalized": []
},
{
"id": "PMID-16268479_T75",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1131,
1135
]
],
"normalized": []
},
{
"id": "PMID-16268479_T76",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
1234,
1237
]
],
"normalized": []
},
{
"id": "PMID-16268479_T79",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
1264,
1267
]
],
"normalized": []
},
{
"id": "PMID-16268479_T80",
"type": "Gene_or_gene_product",
"text": [
"GSK-3alpha"
],
"offsets": [
[
1297,
1307
]
],
"normalized": []
},
{
"id": "PMID-16268479_T81",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
1308,
1311
]
],
"normalized": []
},
{
"id": "PMID-16268479_T85",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
1346,
1349
]
],
"normalized": []
},
{
"id": "PMID-16268479_T86",
"type": "Gene_or_gene_product",
"text": [
"GSK-3alpha"
],
"offsets": [
[
1354,
1364
]
],
"normalized": []
},
{
"id": "PMID-16268479_T89",
"type": "Gene_or_gene_product",
"text": [
"withVEGF"
],
"offsets": [
[
1383,
1391
]
],
"normalized": []
},
{
"id": "PMID-16268479_T90",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
1396,
1399
]
],
"normalized": []
},
{
"id": "PMID-16268479_T91",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
1415,
1418
]
],
"normalized": []
},
{
"id": "PMID-16268479_T92",
"type": "Gene_or_gene_product",
"text": [
"P13-kinase"
],
"offsets": [
[
1423,
1433
]
],
"normalized": []
},
{
"id": "PMID-16268479_T93",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
1461,
1464
]
],
"normalized": []
},
{
"id": "PMID-16268479_T97",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
1472,
1488
]
],
"normalized": []
},
{
"id": "PMID-16268479_T99",
"type": "Gene_or_gene_product",
"text": [
"paxillin"
],
"offsets": [
[
1511,
1519
]
],
"normalized": []
},
{
"id": "PMID-16268479_T102",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1579,
1583
]
],
"normalized": []
},
{
"id": "PMID-16268479_T103",
"type": "Gene_or_gene_product",
"text": [
"S1P"
],
"offsets": [
[
1588,
1591
]
],
"normalized": []
},
{
"id": "PMID-16268479_T104",
"type": "Gene_or_gene_product",
"text": [
"HKa"
],
"offsets": [
[
1619,
1622
]
],
"normalized": []
},
{
"id": "PMID-16268479_T107",
"type": "Gene_or_gene_product",
"text": [
"P13-kinase"
],
"offsets": [
[
1652,
1662
]
],
"normalized": []
},
{
"id": "PMID-16268479_T108",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
1663,
1666
]
],
"normalized": []
},
{
"id": "PMID-16268479_T112",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
1688,
1704
]
],
"normalized": []
},
{
"id": "PMID-16268479_T1000",
"type": "Organism",
"text": [
"bovine"
],
"offsets": [
[
628,
634
]
],
"normalized": []
},
{
"id": "PMID-16268479_T1001",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
679,
684
]
],
"normalized": []
},
{
"id": "PMID-16268479_T1",
"type": "Protein_domain_or_region",
"text": [
"Domain 5"
],
"offsets": [
[
0,
8
]
],
"normalized": []
},
{
"id": "PMID-16268479_T8",
"type": "Protein_domain_or_region",
"text": [
"Domain 5"
],
"offsets": [
[
102,
110
]
],
"normalized": []
},
{
"id": "PMID-16268479_T9",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
112,
114
]
],
"normalized": []
},
{
"id": "PMID-16268479_T21",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
288,
290
]
],
"normalized": []
},
{
"id": "PMID-16268479_T27",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
406,
408
]
],
"normalized": []
},
{
"id": "PMID-16268479_T40",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
617,
619
]
],
"normalized": []
},
{
"id": "PMID-16268479_T55",
"type": "Gene_or_gene_product",
"text": [
"antibodies to urokinase-type plasminogen activator receptor"
],
"offsets": [
[
836,
895
]
],
"normalized": []
},
{
"id": "PMID-16268479_T58",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
910,
912
]
],
"normalized": []
},
{
"id": "PMID-16268479_T69",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
1055,
1057
]
],
"normalized": []
},
{
"id": "PMID-16268479_T82",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
1316,
1318
]
],
"normalized": []
},
{
"id": "PMID-16268479_T105",
"type": "Protein_domain_or_region",
"text": [
"D5"
],
"offsets": [
[
1635,
1637
]
],
"normalized": []
},
{
"id": "PMID-16268479_T50",
"type": "Cellular_component",
"text": [
"focal adhesions"
],
"offsets": [
[
1101,
1116
]
],
"normalized": []
},
{
"id": "PMID-16268479_T109",
"type": "Cellular_component",
"text": [
"focal adhesions"
],
"offsets": [
[
1540,
1555
]
],
"normalized": []
},
{
"id": "PMID-16268479_T114",
"type": "Cellular_component",
"text": [
"focal adhesions"
],
"offsets": [
[
1742,
1757
]
],
"normalized": []
},
{
"id": "PMID-16268479_T115",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
244,
248
]
],
"normalized": []
}
] | [
{
"id": "PMID-16268479_E5",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
78,
87
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T6"
}
]
},
{
"id": "PMID-16268479_E10",
"type": "Protein_processing",
"trigger": {
"text": [
"cleaved"
],
"offsets": [
[
119,
126
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T11"
}
]
},
{
"id": "PMID-16268479_E16",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
216,
225
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T17"
}
]
},
{
"id": "PMID-16268479_E20",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
291,
301
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E23"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_T19"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T21"
}
]
},
{
"id": "PMID-16268479_E23",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
322,
331
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T24"
}
]
},
{
"id": "PMID-16268479_E30",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
466,
475
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T31"
}
]
},
{
"id": "PMID-16268479_E43",
"type": "Localization",
"trigger": {
"text": [
"chemotaxis"
],
"offsets": [
[
717,
727
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T44"
}
]
},
{
"id": "PMID-16268479_E48",
"type": "Localization",
"trigger": {
"text": [
"chemotaxis"
],
"offsets": [
[
717,
727
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T49"
}
]
},
{
"id": "PMID-16268479_E61",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
945,
954
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E64",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1017,
1028
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T67"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E65",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1017,
1028
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T66"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E70",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
1069,
1081
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T71"
},
{
"role": "ToLoc",
"ref_id": "PMID-16268479_T50"
}
]
},
{
"id": "PMID-16268479_E72",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1136,
1147
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T73"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E74",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1136,
1147
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T75"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E77",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1245,
1260
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T80"
}
]
},
{
"id": "PMID-16268479_E78",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1245,
1260
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T79"
}
]
},
{
"id": "PMID-16268479_E83",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1327,
1342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T86"
}
]
},
{
"id": "PMID-16268479_E84",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1327,
1342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T85"
}
]
},
{
"id": "PMID-16268479_E87",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1371,
1382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T90"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E88",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1371,
1382
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T89"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
}
]
},
{
"id": "PMID-16268479_E96",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1489,
1498
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T97"
}
]
},
{
"id": "PMID-16268479_E98",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
1520,
1532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T99"
},
{
"role": "ToLoc",
"ref_id": "PMID-16268479_T109"
}
]
},
{
"id": "PMID-16268479_E101",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1562,
1573
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_T102"
}
]
},
{
"id": "PMID-16268479_E111",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1705,
1714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T112"
}
]
},
{
"id": "PMID-16268479_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
409,
419
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T34"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_E42"
}
]
},
{
"id": "PMID-16268479_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
165,
173
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E16"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_T11"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T8"
}
]
},
{
"id": "PMID-16268479_E3",
"type": "Regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
268,
276
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E20"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_E4"
}
]
},
{
"id": "PMID-16268479_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
409,
419
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T32"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_E42"
}
]
},
{
"id": "PMID-16268479_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
620,
627
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T39"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E48"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T40"
}
]
},
{
"id": "PMID-16268479_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
620,
627
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T39"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E43"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T40"
}
]
},
{
"id": "PMID-16268479_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
762,
770
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T52"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E43"
}
]
},
{
"id": "PMID-16268479_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
762,
770
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T52"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E48"
}
]
},
{
"id": "PMID-16268479_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
762,
770
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T51"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E48"
}
]
},
{
"id": "PMID-16268479_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
762,
770
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T51"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E43"
}
]
},
{
"id": "PMID-16268479_E14",
"type": "Negative_regulation",
"trigger": {
"text": [
"decrease"
],
"offsets": [
[
913,
921
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T57"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E61"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T58"
}
]
},
{
"id": "PMID-16268479_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduce"
],
"offsets": [
[
1058,
1064
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T68"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E70"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T69"
}
]
},
{
"id": "PMID-16268479_E18",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
1224,
1230
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T76"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E77"
}
]
},
{
"id": "PMID-16268479_E19",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
1224,
1230
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T76"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E78"
}
]
},
{
"id": "PMID-16268479_E21",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
1319,
1326
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T81"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E83"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T82"
}
]
},
{
"id": "PMID-16268479_E24",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
1319,
1326
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T81"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E84"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T82"
}
]
},
{
"id": "PMID-16268479_E25",
"type": "Negative_regulation",
"trigger": {
"text": [
"block"
],
"offsets": [
[
1466,
1471
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E96"
}
]
},
{
"id": "PMID-16268479_E26",
"type": "Negative_regulation",
"trigger": {
"text": [
"disrupt"
],
"offsets": [
[
1503,
1510
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E98"
}
]
},
{
"id": "PMID-16268479_E27",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1562,
1573
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T62"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_T103"
}
]
},
{
"id": "PMID-16268479_E28",
"type": "Regulation",
"trigger": {
"text": [
"alters"
],
"offsets": [
[
1645,
1651
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T104"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E34"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T105"
}
]
},
{
"id": "PMID-16268479_E31",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
1680,
1687
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E111"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_E28"
}
]
},
{
"id": "PMID-16268479_E32",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
174,
186
]
]
},
"arguments": []
},
{
"id": "PMID-16268479_E33",
"type": "Pathway",
"trigger": {
"text": [
"signaling pathway"
],
"offsets": [
[
590,
607
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-16268479_T37"
},
{
"role": "Participant",
"ref_id": "PMID-16268479_T38"
}
]
},
{
"id": "PMID-16268479_E34",
"type": "Pathway",
"trigger": {
"text": [
"signaling"
],
"offsets": [
[
1667,
1676
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-16268479_T107"
},
{
"role": "Participant",
"ref_id": "PMID-16268479_T108"
}
]
},
{
"id": "PMID-16268479_E4",
"type": "Pathway",
"trigger": {
"text": [
"signaling pathways"
],
"offsets": [
[
249,
267
]
]
},
"arguments": []
},
{
"id": "PMID-16268479_E15",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
804,
813
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T44"
}
]
},
{
"id": "PMID-16268479_E22",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
790,
800
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T53"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E15"
}
]
},
{
"id": "PMID-16268479_E29",
"type": "Negative_regulation",
"trigger": {
"text": [
"reversed"
],
"offsets": [
[
824,
832
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T55"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E22"
}
]
},
{
"id": "PMID-16268479_E35",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
804,
813
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T49"
}
]
},
{
"id": "PMID-16268479_E36",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
790,
800
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T53"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E35"
}
]
},
{
"id": "PMID-16268479_E37",
"type": "Negative_regulation",
"trigger": {
"text": [
"reversed"
],
"offsets": [
[
824,
832
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T55"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E36"
}
]
},
{
"id": "PMID-16268479_E38",
"type": "Regulation",
"trigger": {
"text": [
"alterations"
],
"offsets": [
[
1723,
1734
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T114"
}
]
},
{
"id": "PMID-16268479_E39",
"type": "Protein_processing",
"trigger": {
"text": [
"cleaved"
],
"offsets": [
[
12,
19
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_T2"
}
]
},
{
"id": "PMID-16268479_E40",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
52,
60
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_E41"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_E5"
}
]
},
{
"id": "PMID-16268479_E41",
"type": "Regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
52,
60
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16268479_T2"
},
{
"role": "Theme",
"ref_id": "PMID-16268479_T7"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T1"
}
]
},
{
"id": "PMID-16268479_E42",
"type": "Regulation",
"trigger": {
"text": [
"act"
],
"offsets": [
[
559,
562
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16268479_E33"
},
{
"role": "Cause",
"ref_id": "PMID-16268479_T25"
},
{
"role": "CSite",
"ref_id": "PMID-16268479_T27"
}
]
}
] | [
{
"id": "PMID-16268479_1",
"entity_ids": [
"PMID-16268479_T32",
"PMID-16268479_T33"
]
},
{
"id": "PMID-16268479_2",
"entity_ids": [
"PMID-16268479_T9",
"PMID-16268479_T8"
]
},
{
"id": "PMID-16268479_3",
"entity_ids": [
"PMID-16268479_T34",
"PMID-16268479_T35"
]
},
{
"id": "PMID-16268479_4",
"entity_ids": [
"PMID-16268479_T11",
"PMID-16268479_T12"
]
},
{
"id": "PMID-16268479_5",
"entity_ids": [
"PMID-16268479_T44",
"PMID-16268479_T46"
]
}
] | [] |
2 | PMID-11121230 | [
{
"id": "PMID-11121230__text",
"type": "abstract",
"text": [
"RNA damage and inhibition of neoplastic endothelial cell growth: effects of human and amphibian ribonucleases.\n\nAngiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels. This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells. To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et al., Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC(50) = 0.3-1.0 microM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC(50) = 0.02-0.06 microM) than on primary HUVECs (IC(50) > 0.1 microM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds.\n"
],
"offsets": [
[
0,
1276
]
]
}
] | [
{
"id": "PMID-11121230_T4",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
40,
56
]
],
"normalized": []
},
{
"id": "PMID-11121230_T5",
"type": "Gene_or_gene_product",
"text": [
"ribonucleases"
],
"offsets": [
[
96,
109
]
],
"normalized": []
},
{
"id": "PMID-11121230_T12",
"type": "Multi-tissue_structure",
"text": [
"blood vessels"
],
"offsets": [
[
213,
226
]
],
"normalized": []
},
{
"id": "PMID-11121230_T14",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
359,
364
]
],
"normalized": []
},
{
"id": "PMID-11121230_T18",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
453,
470
]
],
"normalized": []
},
{
"id": "PMID-11121230_T20",
"type": "Drug_or_compound",
"text": [
"onconase"
],
"offsets": [
[
536,
544
]
],
"normalized": []
},
{
"id": "PMID-11121230_T21",
"type": "Drug_or_compound",
"text": [
"(-4)rhEDN"
],
"offsets": [
[
549,
558
]
],
"normalized": []
},
{
"id": "PMID-11121230_T25",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
595,
611
]
],
"normalized": []
},
{
"id": "PMID-11121230_T26",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
656,
673
]
],
"normalized": []
},
{
"id": "PMID-11121230_T27",
"type": "Cell",
"text": [
"human umbilical vein endothelial cells"
],
"offsets": [
[
712,
750
]
],
"normalized": []
},
{
"id": "PMID-11121230_T28",
"type": "Cell",
"text": [
"HUVECs"
],
"offsets": [
[
752,
758
]
],
"normalized": []
},
{
"id": "PMID-11121230_T29",
"type": "Cell",
"text": [
"HUVEC"
],
"offsets": [
[
793,
798
]
],
"normalized": []
},
{
"id": "PMID-11121230_T30",
"type": "Cell",
"text": [
"HUVECs"
],
"offsets": [
[
859,
865
]
],
"normalized": []
},
{
"id": "PMID-11121230_T31",
"type": "Drug_or_compound",
"text": [
"Onconase"
],
"offsets": [
[
867,
875
]
],
"normalized": []
},
{
"id": "PMID-11121230_T34",
"type": "Drug_or_compound",
"text": [
"(-4)rhEDN"
],
"offsets": [
[
966,
975
]
],
"normalized": []
},
{
"id": "PMID-11121230_T35",
"type": "Cell",
"text": [
"HUVEC cell lines"
],
"offsets": [
[
1011,
1027
]
],
"normalized": []
},
{
"id": "PMID-11121230_T36",
"type": "Cell",
"text": [
"HUVECs"
],
"offsets": [
[
1072,
1078
]
],
"normalized": []
},
{
"id": "PMID-11121230_T37",
"type": "Cell",
"text": [
"endothelial cell type"
],
"offsets": [
[
1170,
1191
]
],
"normalized": []
},
{
"id": "PMID-11121230_T33",
"type": "Pathological_formation",
"text": [
"tumors"
],
"offsets": [
[
287,
293
]
],
"normalized": []
},
{
"id": "PMID-11121230_T13",
"type": "Gene_or_gene_product",
"text": [
"Kras"
],
"offsets": [
[
763,
767
]
],
"normalized": []
},
{
"id": "PMID-11121230_T1000",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
76,
81
]
],
"normalized": []
},
{
"id": "PMID-11121230_T42",
"type": "Organism",
"text": [
"HPV-16 E6"
],
"offsets": [
[
686,
695
]
],
"normalized": []
},
{
"id": "PMID-11121230_T43",
"type": "Organism",
"text": [
"E7"
],
"offsets": [
[
696,
698
]
],
"normalized": []
},
{
"id": "PMID-11121230_T44",
"type": "Organism",
"text": [
"HPV-16 E6"
],
"offsets": [
[
780,
789
]
],
"normalized": []
},
{
"id": "PMID-11121230_T45",
"type": "Organism",
"text": [
"E7"
],
"offsets": [
[
790,
792
]
],
"normalized": []
},
{
"id": "PMID-11121230_T46",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
188,
204
]
],
"normalized": []
},
{
"id": "PMID-11121230_T48",
"type": "Cell",
"text": [
"cell lines"
],
"offsets": [
[
923,
933
]
],
"normalized": []
}
] | [
{
"id": "PMID-11121230_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
15,
25
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_E3"
}
]
},
{
"id": "PMID-11121230_E3",
"type": "Cell_proliferation",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
57,
63
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T4"
}
]
},
{
"id": "PMID-11121230_E9",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
164,
170
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T12"
}
]
},
{
"id": "PMID-11121230_E11",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
175,
184
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T12"
}
]
},
{
"id": "PMID-11121230_E24",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
612,
625
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T25"
}
]
},
{
"id": "PMID-11121230_E4",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
262,
268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T33"
}
]
},
{
"id": "PMID-11121230_E5",
"type": "Localization",
"trigger": {
"text": [
"metastasis"
],
"offsets": [
[
273,
283
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T33"
}
]
},
{
"id": "PMID-11121230_E6",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
584,
591
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_E24"
},
{
"role": "Cause",
"ref_id": "PMID-11121230_T21"
}
]
},
{
"id": "PMID-11121230_E7",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
584,
591
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_E24"
},
{
"role": "Cause",
"ref_id": "PMID-11121230_T20"
}
]
},
{
"id": "PMID-11121230_E12",
"type": "Planned_process",
"trigger": {
"text": [
"immortalized"
],
"offsets": [
[
699,
711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T27"
},
{
"role": "Instrument",
"ref_id": "PMID-11121230_T43"
}
]
},
{
"id": "PMID-11121230_E13",
"type": "Planned_process",
"trigger": {
"text": [
"immortalized"
],
"offsets": [
[
699,
711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T27"
},
{
"role": "Instrument",
"ref_id": "PMID-11121230_T42"
}
]
},
{
"id": "PMID-11121230_E14",
"type": "Planned_process",
"trigger": {
"text": [
"transformed"
],
"offsets": [
[
768,
779
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-11121230_T13"
},
{
"role": "Theme",
"ref_id": "PMID-11121230_T29"
}
]
},
{
"id": "PMID-11121230_E15",
"type": "Planned_process",
"trigger": {
"text": [
"immortalized"
],
"offsets": [
[
998,
1010
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T35"
}
]
},
{
"id": "PMID-11121230_E16",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
1208,
1221
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T37"
}
]
},
{
"id": "PMID-11121230_E17",
"type": "Development",
"trigger": {
"text": [
"derived"
],
"offsets": [
[
205,
212
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T12"
}
]
},
{
"id": "PMID-11121230_E18",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
896,
909
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11121230_T48"
}
]
},
{
"id": "PMID-11121230_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
886,
895
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11121230_T31"
},
{
"role": "Theme",
"ref_id": "PMID-11121230_E18"
}
]
},
{
"id": "PMID-11121230_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"effective"
],
"offsets": [
[
985,
994
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11121230_T34"
},
{
"role": "Theme",
"ref_id": "PMID-11121230_T35"
}
]
},
{
"id": "PMID-11121230_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"effective"
],
"offsets": [
[
985,
994
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11121230_T34"
},
{
"role": "Theme",
"ref_id": "PMID-11121230_T36"
}
]
},
{
"id": "PMID-11121230_E22",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
112,
124
]
]
},
"arguments": []
},
{
"id": "PMID-11121230_E25",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
365,
377
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-11121230_T14"
}
]
},
{
"id": "PMID-11121230_E26",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
429,
439
]
]
},
"arguments": []
},
{
"id": "PMID-11121230_E27",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
504,
514
]
]
},
"arguments": []
},
{
"id": "PMID-11121230_E28",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1254,
1264
]
]
},
"arguments": []
}
] | [
{
"id": "PMID-11121230_1",
"entity_ids": [
"PMID-11121230_T27",
"PMID-11121230_T28"
]
}
] | [
{
"id": "PMID-11121230_R1",
"type": "frag",
"arg1_id": "PMID-11121230_T43",
"arg2_id": "PMID-11121230_T42",
"normalized": []
},
{
"id": "PMID-11121230_R2",
"type": "frag",
"arg1_id": "PMID-11121230_T45",
"arg2_id": "PMID-11121230_T44",
"normalized": []
}
] |
3 | PMID-12610665 | [
{
"id": "PMID-12610665__text",
"type": "abstract",
"text": [
"Arteriogenesis: the development and growth of collateral arteries.\n\nIn patients with atherosclerotic vascular diseases, collateral vessels bypassing major arterial obstructions have frequently been observed. This may explain why some patients remain without symptoms or signs of ischemia. The term \"arteriogenesis\" was introduced to differentiate the formation of collateral arteries from angiogenesis, which mainly occurs in the ischemic, collateral flow-dependent tissue. Many observations in various animal models and humans support that the remodeling of preexisting collateral vessels is the mechanism of collateral artery formation. This remodeling process seems to be mainly flow-mediated. It involves endothelial cell activation, basal membrane degradation, leukocyte invasion, proliferation of vascular cells, neointima formation (in most species studied), and changes of the extracellular matrix. The contribution of ischemia to arteriogenesis is still unclear, but arteriogenesis clearly can occur in the absence of any significant ischemia. It is questionable, whether collateral arteries also form de novo in ischemic vascular diseases. A better understanding of the mechanisms of arteriogenesis will be important for the design of more effective strategies for the treatment of patients with ischemic vascular diseases.\n"
],
"offsets": [
[
0,
1334
]
]
}
] | [
{
"id": "PMID-12610665_T2",
"type": "Multi-tissue_structure",
"text": [
"collateral arteries"
],
"offsets": [
[
46,
65
]
],
"normalized": []
},
{
"id": "PMID-12610665_T3",
"type": "Multi-tissue_structure",
"text": [
"collateral vessels"
],
"offsets": [
[
120,
138
]
],
"normalized": []
},
{
"id": "PMID-12610665_T5",
"type": "Multi-tissue_structure",
"text": [
"collateral arteries"
],
"offsets": [
[
364,
383
]
],
"normalized": []
},
{
"id": "PMID-12610665_T7",
"type": "Multi-tissue_structure",
"text": [
"collateral vessels"
],
"offsets": [
[
571,
589
]
],
"normalized": []
},
{
"id": "PMID-12610665_T8",
"type": "Multi-tissue_structure",
"text": [
"collateral artery"
],
"offsets": [
[
610,
627
]
],
"normalized": []
},
{
"id": "PMID-12610665_T11",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
709,
725
]
],
"normalized": []
},
{
"id": "PMID-12610665_T12",
"type": "Cellular_component",
"text": [
"basal membrane"
],
"offsets": [
[
738,
752
]
],
"normalized": []
},
{
"id": "PMID-12610665_T13",
"type": "Cell",
"text": [
"leukocyte"
],
"offsets": [
[
766,
775
]
],
"normalized": []
},
{
"id": "PMID-12610665_T16",
"type": "Cell",
"text": [
"vascular cells"
],
"offsets": [
[
803,
817
]
],
"normalized": []
},
{
"id": "PMID-12610665_T20",
"type": "Tissue",
"text": [
"neointima"
],
"offsets": [
[
819,
828
]
],
"normalized": []
},
{
"id": "PMID-12610665_T21",
"type": "Cellular_component",
"text": [
"extracellular matrix"
],
"offsets": [
[
885,
905
]
],
"normalized": []
},
{
"id": "PMID-12610665_T25",
"type": "Multi-tissue_structure",
"text": [
"collateral arteries"
],
"offsets": [
[
1081,
1100
]
],
"normalized": []
},
{
"id": "PMID-12610665_T1000",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
71,
79
]
],
"normalized": []
},
{
"id": "PMID-12610665_T1001",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
234,
242
]
],
"normalized": []
},
{
"id": "PMID-12610665_T1002",
"type": "Organism",
"text": [
"humans"
],
"offsets": [
[
521,
527
]
],
"normalized": []
},
{
"id": "PMID-12610665_T1003",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1292,
1300
]
],
"normalized": []
},
{
"id": "PMID-12610665_T35",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
466,
472
]
],
"normalized": []
},
{
"id": "PMID-12610665_T9",
"type": "Pathological_formation",
"text": [
"arterial obstructions"
],
"offsets": [
[
155,
176
]
],
"normalized": []
}
] | [
{
"id": "PMID-12610665_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
726,
736
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T11"
}
]
},
{
"id": "PMID-12610665_E15",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
786,
799
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T16"
}
]
},
{
"id": "PMID-12610665_E19",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
829,
838
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T20"
}
]
},
{
"id": "PMID-12610665_E1",
"type": "Development",
"trigger": {
"text": [
"development"
],
"offsets": [
[
20,
31
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T2"
}
]
},
{
"id": "PMID-12610665_E2",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
36,
42
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T2"
}
]
},
{
"id": "PMID-12610665_E3",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
351,
360
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T5"
}
]
},
{
"id": "PMID-12610665_E4",
"type": "Remodeling",
"trigger": {
"text": [
"remodeling"
],
"offsets": [
[
545,
555
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T7"
}
]
},
{
"id": "PMID-12610665_E5",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
628,
637
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T8"
}
]
},
{
"id": "PMID-12610665_E6",
"type": "Remodeling",
"trigger": {
"text": [
"remodeling"
],
"offsets": [
[
644,
654
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T7"
}
]
},
{
"id": "PMID-12610665_E7",
"type": "Breakdown",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
753,
764
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T12"
}
]
},
{
"id": "PMID-12610665_E8",
"type": "Localization",
"trigger": {
"text": [
"invasion"
],
"offsets": [
[
776,
784
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T13"
}
]
},
{
"id": "PMID-12610665_E11",
"type": "Regulation",
"trigger": {
"text": [
"changes"
],
"offsets": [
[
870,
877
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T21"
}
]
},
{
"id": "PMID-12610665_E12",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E10"
}
]
},
{
"id": "PMID-12610665_E13",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E7"
}
]
},
{
"id": "PMID-12610665_E16",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E8"
}
]
},
{
"id": "PMID-12610665_E17",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E15"
}
]
},
{
"id": "PMID-12610665_E20",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E19"
}
]
},
{
"id": "PMID-12610665_E21",
"type": "Regulation",
"trigger": {
"text": [
"involves"
],
"offsets": [
[
700,
708
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12610665_E6"
},
{
"role": "Theme",
"ref_id": "PMID-12610665_E11"
}
]
},
{
"id": "PMID-12610665_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
456,
465
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T35"
}
]
},
{
"id": "PMID-12610665_E23",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Arteriogenesis"
],
"offsets": [
[
0,
14
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T2"
}
]
},
{
"id": "PMID-12610665_E24",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"arteriogenesis"
],
"offsets": [
[
299,
313
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T5"
}
]
},
{
"id": "PMID-12610665_E25",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
389,
401
]
]
},
"arguments": []
},
{
"id": "PMID-12610665_E26",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"arteriogenesis"
],
"offsets": [
[
939,
953
]
]
},
"arguments": []
},
{
"id": "PMID-12610665_E27",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"arteriogenesis"
],
"offsets": [
[
976,
990
]
]
},
"arguments": []
},
{
"id": "PMID-12610665_E28",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"arteriogenesis"
],
"offsets": [
[
1194,
1208
]
]
},
"arguments": []
},
{
"id": "PMID-12610665_E9",
"type": "Development",
"trigger": {
"text": [
"form"
],
"offsets": [
[
1106,
1110
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12610665_T25"
}
]
}
] | [] | [] |
4 | PMID-17462601 | [
{
"id": "PMID-17462601__text",
"type": "abstract",
"text": [
"An antibody directed against PDGF receptor beta enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibody.\n\nPlatelet-derived growth factor (PDGF) and its receptors (PDGFR) play important roles in tumorigenesis through stimulating tumor growth and promoting angiogenesis via enhancing pericyte recruitment and vessel maturation. Here we produced a neutralizing antibody, 1B3, directed against mouse PDGFRbeta. 1B3 binds to PDGFRbeta with high affinity (9x10(-11)M) and blocks PDGF-BB from binding to the receptor with an IC(50) of approximately 1.2 nM. The antibody also blocks ligand-stimulated activation of PDGFRbeta and downstream signaling molecules, including Akt and MAPK p42/44, in tumor cells. In animal studies, 1B3 significantly enhanced the antitumor and the anti-angiogenic activities of DC101, an antibody directed against mouse vascular endothelial growth factor receptor 2, in a pancreatic (BxPC-3) and a non-small cell lung (NCI-H460) tumor xenograft models. Treatment with the combination of 1B3 and DC101 in BxPC-3 xenograft-bearing mice resulted in tumor regression in 58% of mice compared to that in 18% of mice treated with DC101 alone. Taken together, these results lend great support to use PDGFRbeta antagonists in combinations with other antitumor and/or anti-angiogenic agents in the treatment of a variety of cancers.\n"
],
"offsets": [
[
0,
1381
]
]
}
] | [
{
"id": "PMID-17462601_T1",
"type": "Gene_or_gene_product",
"text": [
"PDGF receptor beta"
],
"offsets": [
[
29,
47
]
],
"normalized": []
},
{
"id": "PMID-17462601_T6",
"type": "Gene_or_gene_product",
"text": [
"VEGF receptor 2"
],
"offsets": [
[
117,
132
]
],
"normalized": []
},
{
"id": "PMID-17462601_T7",
"type": "Gene_or_gene_product",
"text": [
"Platelet-derived growth factor"
],
"offsets": [
[
144,
174
]
],
"normalized": []
},
{
"id": "PMID-17462601_T8",
"type": "Gene_or_gene_product",
"text": [
"PDGF"
],
"offsets": [
[
176,
180
]
],
"normalized": []
},
{
"id": "PMID-17462601_T9",
"type": "Gene_or_gene_product",
"text": [
"PDGFR"
],
"offsets": [
[
201,
206
]
],
"normalized": []
},
{
"id": "PMID-17462601_T12",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
266,
271
]
],
"normalized": []
},
{
"id": "PMID-17462601_T16",
"type": "Cell",
"text": [
"pericyte"
],
"offsets": [
[
320,
328
]
],
"normalized": []
},
{
"id": "PMID-17462601_T18",
"type": "Multi-tissue_structure",
"text": [
"vessel"
],
"offsets": [
[
345,
351
]
],
"normalized": []
},
{
"id": "PMID-17462601_T19",
"type": "Drug_or_compound",
"text": [
"1B3"
],
"offsets": [
[
406,
409
]
],
"normalized": []
},
{
"id": "PMID-17462601_T20",
"type": "Gene_or_gene_product",
"text": [
"PDGFRbeta"
],
"offsets": [
[
434,
443
]
],
"normalized": []
},
{
"id": "PMID-17462601_T22",
"type": "Drug_or_compound",
"text": [
"1B3"
],
"offsets": [
[
445,
448
]
],
"normalized": []
},
{
"id": "PMID-17462601_T23",
"type": "Gene_or_gene_product",
"text": [
"PDGFRbeta"
],
"offsets": [
[
458,
467
]
],
"normalized": []
},
{
"id": "PMID-17462601_T24",
"type": "Gene_or_gene_product",
"text": [
"PDGF-BB"
],
"offsets": [
[
511,
518
]
],
"normalized": []
},
{
"id": "PMID-17462601_T26",
"type": "Gene_or_gene_product",
"text": [
"PDGFRbeta"
],
"offsets": [
[
645,
654
]
],
"normalized": []
},
{
"id": "PMID-17462601_T27",
"type": "Gene_or_gene_product",
"text": [
"Akt"
],
"offsets": [
[
701,
704
]
],
"normalized": []
},
{
"id": "PMID-17462601_T28",
"type": "Gene_or_gene_product",
"text": [
"MAPK p42/44"
],
"offsets": [
[
709,
720
]
],
"normalized": []
},
{
"id": "PMID-17462601_T29",
"type": "Cell",
"text": [
"tumor cells"
],
"offsets": [
[
725,
736
]
],
"normalized": []
},
{
"id": "PMID-17462601_T31",
"type": "Drug_or_compound",
"text": [
"1B3"
],
"offsets": [
[
757,
760
]
],
"normalized": []
},
{
"id": "PMID-17462601_T34",
"type": "Drug_or_compound",
"text": [
"DC101"
],
"offsets": [
[
836,
841
]
],
"normalized": []
},
{
"id": "PMID-17462601_T35",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor receptor 2"
],
"offsets": [
[
878,
923
]
],
"normalized": []
},
{
"id": "PMID-17462601_T36",
"type": "Pathological_formation",
"text": [
"BxPC-3"
],
"offsets": [
[
942,
948
]
],
"normalized": []
},
{
"id": "PMID-17462601_T39",
"type": "Pathological_formation",
"text": [
"non-small cell lung (NCI-H460) tumor xenograft"
],
"offsets": [
[
956,
1002
]
],
"normalized": []
},
{
"id": "PMID-17462601_T40",
"type": "Drug_or_compound",
"text": [
"1B3"
],
"offsets": [
[
1045,
1048
]
],
"normalized": []
},
{
"id": "PMID-17462601_T41",
"type": "Drug_or_compound",
"text": [
"DC101"
],
"offsets": [
[
1053,
1058
]
],
"normalized": []
},
{
"id": "PMID-17462601_T42",
"type": "Pathological_formation",
"text": [
"BxPC-3 xenograft"
],
"offsets": [
[
1062,
1078
]
],
"normalized": []
},
{
"id": "PMID-17462601_T44",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1104,
1109
]
],
"normalized": []
},
{
"id": "PMID-17462601_T45",
"type": "Drug_or_compound",
"text": [
"DC101"
],
"offsets": [
[
1181,
1186
]
],
"normalized": []
},
{
"id": "PMID-17462601_T47",
"type": "Gene_or_gene_product",
"text": [
"PDGFRbeta"
],
"offsets": [
[
1250,
1259
]
],
"normalized": []
},
{
"id": "PMID-17462601_T2",
"type": "Pathological_formation",
"text": [
"pancreatic"
],
"offsets": [
[
930,
940
]
],
"normalized": []
},
{
"id": "PMID-17462601_T3",
"type": "Pathological_formation",
"text": [
"cancers"
],
"offsets": [
[
1372,
1379
]
],
"normalized": []
},
{
"id": "PMID-17462601_T1000",
"type": "Organism",
"text": [
"mouse"
],
"offsets": [
[
428,
433
]
],
"normalized": []
},
{
"id": "PMID-17462601_T1001",
"type": "Organism",
"text": [
"mouse"
],
"offsets": [
[
872,
877
]
],
"normalized": []
},
{
"id": "PMID-17462601_T1002",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1087,
1091
]
],
"normalized": []
},
{
"id": "PMID-17462601_T1003",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1131,
1135
]
],
"normalized": []
},
{
"id": "PMID-17462601_T1004",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1163,
1167
]
],
"normalized": []
},
{
"id": "PMID-17462601_T5",
"type": "Gene_or_gene_product",
"text": [
"anti-VEGF receptor 2 antibody"
],
"offsets": [
[
112,
141
]
],
"normalized": []
},
{
"id": "PMID-17462601_T58",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
65,
70
]
],
"normalized": []
},
{
"id": "PMID-17462601_T59",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
792,
797
]
],
"normalized": []
},
{
"id": "PMID-17462601_T61",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1303,
1308
]
],
"normalized": []
}
] | [
{
"id": "PMID-17462601_E11",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
272,
278
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T12"
}
]
},
{
"id": "PMID-17462601_E21",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
449,
454
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T22"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T23"
}
]
},
{
"id": "PMID-17462601_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
631,
641
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T26"
}
]
},
{
"id": "PMID-17462601_E43",
"type": "Negative_regulation",
"trigger": {
"text": [
"regression"
],
"offsets": [
[
1110,
1120
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T44"
}
]
},
{
"id": "PMID-17462601_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhances"
],
"offsets": [
[
48,
56
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T1"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T5"
}
]
},
{
"id": "PMID-17462601_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulating"
],
"offsets": [
[
254,
265
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T9"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E11"
}
]
},
{
"id": "PMID-17462601_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"promoting"
],
"offsets": [
[
283,
292
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_E31"
}
]
},
{
"id": "PMID-17462601_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancing"
],
"offsets": [
[
310,
319
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_E7"
}
]
},
{
"id": "PMID-17462601_E6",
"type": "Development",
"trigger": {
"text": [
"maturation"
],
"offsets": [
[
352,
362
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T18"
}
]
},
{
"id": "PMID-17462601_E7",
"type": "Localization",
"trigger": {
"text": [
"recruitment"
],
"offsets": [
[
329,
340
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T16"
}
]
},
{
"id": "PMID-17462601_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulating"
],
"offsets": [
[
254,
265
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T7"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E11"
}
]
},
{
"id": "PMID-17462601_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulating"
],
"offsets": [
[
254,
265
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T9"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E4"
}
]
},
{
"id": "PMID-17462601_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulating"
],
"offsets": [
[
254,
265
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T7"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E4"
}
]
},
{
"id": "PMID-17462601_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancing"
],
"offsets": [
[
310,
319
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_E6"
}
]
},
{
"id": "PMID-17462601_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancing"
],
"offsets": [
[
310,
319
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T9"
}
]
},
{
"id": "PMID-17462601_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhancing"
],
"offsets": [
[
310,
319
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T7"
}
]
},
{
"id": "PMID-17462601_E15",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocks"
],
"offsets": [
[
504,
510
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_E16"
},
{
"role": "Cause",
"ref_id": "PMID-17462601_T22"
}
]
},
{
"id": "PMID-17462601_E16",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
524,
531
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T24"
}
]
},
{
"id": "PMID-17462601_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocks"
],
"offsets": [
[
606,
612
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T22"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E25"
}
]
},
{
"id": "PMID-17462601_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
631,
641
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T27"
}
]
},
{
"id": "PMID-17462601_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
631,
641
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T28"
}
]
},
{
"id": "PMID-17462601_E22",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocks"
],
"offsets": [
[
606,
612
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T22"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E19"
}
]
},
{
"id": "PMID-17462601_E23",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocks"
],
"offsets": [
[
606,
612
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T22"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E20"
}
]
},
{
"id": "PMID-17462601_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
775,
783
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T31"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E38"
}
]
},
{
"id": "PMID-17462601_E26",
"type": "Planned_process",
"trigger": {
"text": [
"Treatment"
],
"offsets": [
[
1011,
1020
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-17462601_T40"
},
{
"role": "Instrument",
"ref_id": "PMID-17462601_T41"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T1002"
}
]
},
{
"id": "PMID-17462601_E27",
"type": "Positive_regulation",
"trigger": {
"text": [
"resulted"
],
"offsets": [
[
1092,
1100
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_E26"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E43"
}
]
},
{
"id": "PMID-17462601_E28",
"type": "Planned_process",
"trigger": {
"text": [
"treated"
],
"offsets": [
[
1168,
1175
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-17462601_T45"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T1004"
}
]
},
{
"id": "PMID-17462601_E29",
"type": "Planned_process",
"trigger": {
"text": [
"treatment"
],
"offsets": [
[
1346,
1355
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-17462601_T3"
}
]
},
{
"id": "PMID-17462601_E30",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
84,
94
]
]
},
"arguments": []
},
{
"id": "PMID-17462601_E31",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
293,
305
]
]
},
"arguments": []
},
{
"id": "PMID-17462601_E32",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
811,
821
]
]
},
"arguments": []
},
{
"id": "PMID-17462601_E33",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1321,
1331
]
]
},
"arguments": []
},
{
"id": "PMID-17462601_E34",
"type": "Negative_regulation",
"trigger": {
"text": [
"activities"
],
"offsets": [
[
95,
105
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T5"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E30"
}
]
},
{
"id": "PMID-17462601_E35",
"type": "Negative_regulation",
"trigger": {
"text": [
"activities"
],
"offsets": [
[
95,
105
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T5"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T58"
}
]
},
{
"id": "PMID-17462601_E36",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhances"
],
"offsets": [
[
48,
56
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T1"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E34"
}
]
},
{
"id": "PMID-17462601_E37",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhances"
],
"offsets": [
[
48,
56
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T1"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E35"
}
]
},
{
"id": "PMID-17462601_E38",
"type": "Negative_regulation",
"trigger": {
"text": [
"activities"
],
"offsets": [
[
822,
832
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T34"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E32"
}
]
},
{
"id": "PMID-17462601_E39",
"type": "Negative_regulation",
"trigger": {
"text": [
"activities"
],
"offsets": [
[
822,
832
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T34"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_T59"
}
]
},
{
"id": "PMID-17462601_E40",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
775,
783
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-17462601_T31"
},
{
"role": "Theme",
"ref_id": "PMID-17462601_E39"
}
]
}
] | [
{
"id": "PMID-17462601_1",
"entity_ids": [
"PMID-17462601_T7",
"PMID-17462601_T8"
]
}
] | [
{
"id": "PMID-17462601_R1",
"type": "frag",
"arg1_id": "PMID-17462601_T2",
"arg2_id": "PMID-17462601_T39",
"normalized": []
}
] |
5 | PMID-19369582 | [
{
"id": "PMID-19369582__text",
"type": "abstract",
"text": [
"Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets.\n\nAngiogenesis is a fundamental process to normal and abnormal tissue growth and repair, which consists of recruiting endothelial cells toward an angiogenic stimulus. The cells subsequently proliferate and differentiate to form endothelial tubes and capillary-like structures. Little is known about the metabolic adaptation of endothelial cells through such a transformation. We studied the metabolic changes of endothelial cell activation by growth factors using human umbilical vein endothelial cells (HUVECs), [1,2-(13)C(2)]-glucose and mass isotopomer distribution analysis. The metabolism of [1,2-(13)C(2)]-glucose by HUVEC allows us to trace many of the main glucose metabolic pathways, including glycogen synthesis, the pentose cycle and the glycolytic pathways. So we established that these pathways were crucial to endothelial cell proliferation under vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) stimulation. A specific VEGF receptor-2 inhibitor demonstrated the importance of glycogen metabolism and pentose cycle pathway. Furthermore, we showed that glycogen was depleted in a low glucose medium, but conserved under hypoxic conditions. Finally, we demonstrated that direct inhibition of key enzymes to glycogen metabolism and pentose phosphate pathways reduced HUVEC viability and migration. In this regard, inhibitors of these pathways have been shown to be effective antitumoral agents. To sum up, our data suggest that the inhibition of metabolic pathways offers a novel and powerful therapeutic approach, which simultaneously inhibits tumor cell proliferation and tumor-induced angiogenesis.\n"
],
"offsets": [
[
0,
1783
]
]
}
] | [
{
"id": "PMID-19369582_T3",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
260,
277
]
],
"normalized": []
},
{
"id": "PMID-19369582_T6",
"type": "Tissue",
"text": [
"endothelial tubes"
],
"offsets": [
[
370,
387
]
],
"normalized": []
},
{
"id": "PMID-19369582_T7",
"type": "Tissue",
"text": [
"capillary-like structures"
],
"offsets": [
[
392,
417
]
],
"normalized": []
},
{
"id": "PMID-19369582_T8",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
469,
486
]
],
"normalized": []
},
{
"id": "PMID-19369582_T10",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
554,
570
]
],
"normalized": []
},
{
"id": "PMID-19369582_T11",
"type": "Cell",
"text": [
"human umbilical vein endothelial cells"
],
"offsets": [
[
606,
644
]
],
"normalized": []
},
{
"id": "PMID-19369582_T12",
"type": "Cell",
"text": [
"HUVECs"
],
"offsets": [
[
646,
652
]
],
"normalized": []
},
{
"id": "PMID-19369582_T13",
"type": "Drug_or_compound",
"text": [
"[1,2-(13)C(2)]-glucose"
],
"offsets": [
[
655,
677
]
],
"normalized": []
},
{
"id": "PMID-19369582_T15",
"type": "Drug_or_compound",
"text": [
"[1,2-(13)C(2)]-glucose"
],
"offsets": [
[
739,
761
]
],
"normalized": []
},
{
"id": "PMID-19369582_T16",
"type": "Cell",
"text": [
"HUVEC"
],
"offsets": [
[
765,
770
]
],
"normalized": []
},
{
"id": "PMID-19369582_T17",
"type": "Drug_or_compound",
"text": [
"glucose"
],
"offsets": [
[
807,
814
]
],
"normalized": []
},
{
"id": "PMID-19369582_T23",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
966,
982
]
],
"normalized": []
},
{
"id": "PMID-19369582_T25",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
1003,
1037
]
],
"normalized": []
},
{
"id": "PMID-19369582_T26",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1039,
1043
]
],
"normalized": []
},
{
"id": "PMID-19369582_T28",
"type": "Gene_or_gene_product",
"text": [
"fibroblast growth factor"
],
"offsets": [
[
1049,
1073
]
],
"normalized": []
},
{
"id": "PMID-19369582_T29",
"type": "Gene_or_gene_product",
"text": [
"FGF"
],
"offsets": [
[
1075,
1078
]
],
"normalized": []
},
{
"id": "PMID-19369582_T30",
"type": "Gene_or_gene_product",
"text": [
"VEGF receptor-2"
],
"offsets": [
[
1104,
1119
]
],
"normalized": []
},
{
"id": "PMID-19369582_T33",
"type": "Drug_or_compound",
"text": [
"glucose"
],
"offsets": [
[
1267,
1274
]
],
"normalized": []
},
{
"id": "PMID-19369582_T37",
"type": "Cell",
"text": [
"HUVEC"
],
"offsets": [
[
1448,
1453
]
],
"normalized": []
},
{
"id": "PMID-19369582_T38",
"type": "Cell",
"text": [
"tumor cell"
],
"offsets": [
[
1726,
1736
]
],
"normalized": []
},
{
"id": "PMID-19369582_T40",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1755,
1760
]
],
"normalized": []
},
{
"id": "PMID-19369582_T50",
"type": "Drug_or_compound",
"text": [
"glycogen"
],
"offsets": [
[
845,
853
]
],
"normalized": []
},
{
"id": "PMID-19369582_T52",
"type": "Drug_or_compound",
"text": [
"pentose"
],
"offsets": [
[
869,
876
]
],
"normalized": []
},
{
"id": "PMID-19369582_T27",
"type": "Drug_or_compound",
"text": [
"glycogen"
],
"offsets": [
[
1236,
1244
]
],
"normalized": []
},
{
"id": "PMID-19369582_T55",
"type": "Drug_or_compound",
"text": [
"glycogen"
],
"offsets": [
[
1389,
1397
]
],
"normalized": []
},
{
"id": "PMID-19369582_T57",
"type": "Drug_or_compound",
"text": [
"pentose"
],
"offsets": [
[
1413,
1420
]
],
"normalized": []
},
{
"id": "PMID-19369582_T63",
"type": "Tissue",
"text": [
"tissue"
],
"offsets": [
[
205,
211
]
],
"normalized": []
},
{
"id": "PMID-19369582_T66",
"type": "Cell",
"text": [
"cells"
],
"offsets": [
[
313,
318
]
],
"normalized": []
},
{
"id": "PMID-19369582_T18",
"type": "Drug_or_compound",
"text": [
"glycogen"
],
"offsets": [
[
1161,
1169
]
],
"normalized": []
},
{
"id": "PMID-19369582_T53",
"type": "Drug_or_compound",
"text": [
"pentose"
],
"offsets": [
[
1185,
1192
]
],
"normalized": []
}
] | [
{
"id": "PMID-19369582_E14",
"type": "Metabolism",
"trigger": {
"text": [
"metabolism"
],
"offsets": [
[
725,
735
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T15"
}
]
},
{
"id": "PMID-19369582_E22",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
983,
996
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T23"
}
]
},
{
"id": "PMID-19369582_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1080,
1091
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T28"
}
]
},
{
"id": "PMID-19369582_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
78,
88
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_E30"
}
]
},
{
"id": "PMID-19369582_E2",
"type": "Localization",
"trigger": {
"text": [
"recruiting"
],
"offsets": [
[
249,
259
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T3"
}
]
},
{
"id": "PMID-19369582_E3",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferate"
],
"offsets": [
[
332,
343
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T66"
}
]
},
{
"id": "PMID-19369582_E4",
"type": "Development",
"trigger": {
"text": [
"differentiate"
],
"offsets": [
[
348,
361
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T66"
}
]
},
{
"id": "PMID-19369582_E6",
"type": "Development",
"trigger": {
"text": [
"form"
],
"offsets": [
[
365,
369
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T6"
}
]
},
{
"id": "PMID-19369582_E7",
"type": "Development",
"trigger": {
"text": [
"form"
],
"offsets": [
[
365,
369
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T7"
}
]
},
{
"id": "PMID-19369582_E8",
"type": "Development",
"trigger": {
"text": [
"transformation"
],
"offsets": [
[
502,
516
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T8"
}
]
},
{
"id": "PMID-19369582_E10",
"type": "Regulation",
"trigger": {
"text": [
"changes"
],
"offsets": [
[
543,
550
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_E11"
}
]
},
{
"id": "PMID-19369582_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
571,
581
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T10"
}
]
},
{
"id": "PMID-19369582_E12",
"type": "Pathway",
"trigger": {
"text": [
"metabolic pathways"
],
"offsets": [
[
815,
833
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19369582_T17"
}
]
},
{
"id": "PMID-19369582_E13",
"type": "Synthesis",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
854,
863
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T50"
}
]
},
{
"id": "PMID-19369582_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1080,
1091
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T25"
}
]
},
{
"id": "PMID-19369582_E17",
"type": "Catabolism",
"trigger": {
"text": [
"depleted"
],
"offsets": [
[
1249,
1257
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T27"
}
]
},
{
"id": "PMID-19369582_E18",
"type": "Metabolism",
"trigger": {
"text": [
"metabolism"
],
"offsets": [
[
1398,
1408
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T55"
}
]
},
{
"id": "PMID-19369582_E19",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1440,
1447
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_E20"
}
]
},
{
"id": "PMID-19369582_E20",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1468,
1477
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T37"
}
]
},
{
"id": "PMID-19369582_E23",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
1717,
1725
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_E25"
}
]
},
{
"id": "PMID-19369582_E25",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
1737,
1750
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T38"
}
]
},
{
"id": "PMID-19369582_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1761,
1768
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-19369582_T40"
},
{
"role": "Theme",
"ref_id": "PMID-19369582_E33"
}
]
},
{
"id": "PMID-19369582_E27",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
1717,
1725
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_E33"
}
]
},
{
"id": "PMID-19369582_E28",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
212,
218
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T63"
}
]
},
{
"id": "PMID-19369582_E29",
"type": "Development",
"trigger": {
"text": [
"repair"
],
"offsets": [
[
223,
229
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T63"
}
]
},
{
"id": "PMID-19369582_E30",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
67,
77
]
]
},
"arguments": []
},
{
"id": "PMID-19369582_E31",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
144,
156
]
]
},
"arguments": []
},
{
"id": "PMID-19369582_E32",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
288,
298
]
]
},
"arguments": []
},
{
"id": "PMID-19369582_E33",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1769,
1781
]
]
},
"arguments": []
},
{
"id": "PMID-19369582_E37",
"type": "Pathway",
"trigger": {
"text": [
"glycolytic pathways"
],
"offsets": [
[
891,
910
]
]
},
"arguments": []
},
{
"id": "PMID-19369582_E39",
"type": "Pathway",
"trigger": {
"text": [
"cycle pathway"
],
"offsets": [
[
1193,
1206
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19369582_T53"
}
]
},
{
"id": "PMID-19369582_E41",
"type": "Pathway",
"trigger": {
"text": [
"phosphate pathways"
],
"offsets": [
[
1421,
1439
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19369582_T57"
}
]
},
{
"id": "PMID-19369582_E34",
"type": "Metabolism",
"trigger": {
"text": [
"metabolism"
],
"offsets": [
[
1170,
1180
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19369582_T18"
}
]
},
{
"id": "PMID-19369582_E15",
"type": "Pathway",
"trigger": {
"text": [
"cycle"
],
"offsets": [
[
877,
882
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19369582_T52"
}
]
}
] | [
{
"id": "PMID-19369582_1",
"entity_ids": [
"PMID-19369582_T11",
"PMID-19369582_T12"
]
},
{
"id": "PMID-19369582_2",
"entity_ids": [
"PMID-19369582_T25",
"PMID-19369582_T26"
]
},
{
"id": "PMID-19369582_3",
"entity_ids": [
"PMID-19369582_T28",
"PMID-19369582_T29"
]
}
] | [] |
6 | PMID-10589785 | [
{
"id": "PMID-10589785__text",
"type": "abstract",
"text": [
"The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice.\n\nThe aim of this study was to ascertain the potential usefulness of the antiangiogenic compound linomide for treatment of von Hippel-Lindau (VHL)-related tumors. Paraganglioma tissue fragments obtained at surgery from a VHL type 2a patient were transplanted s.c. to male BALB/c nu/nu (nude) mice: (a) 2-3-mm fragments for \"prevention\" experiments; and (b) 2-3-mm fragments allowed to grow to 1 cm for \"intervention\" studies. Both groups received either 0.5 mg/ml linomide in drinking water or acidified water and were followed until tumor diameter reached 3 cm or for 4 weeks. In both the prevention and intervention experiments, a significant diminution of tumor size and weight was observed in the drug-treated animals. In vivo nuclear magnetic resonance analysis of tumor blood flow in linomide-treated animals showed localization of blood vessels almost exclusively to the periphery of the poorly vascularized tumors with a significant reduction of both vascular functionality and vasodilation. Histological examination of tumors from linomide-treated animals revealed marked avascularity. Treated animals also displayed a 2.4-fold reduction of tumor vascular endothelial growth factor mRNA levels. Taken together, our data indicate that in VHL disease, therapy directed at inhibition of constitutively expressed VEGF induction of angiogenesis by VHL tumors may constitute an effective medical treatment.\n"
],
"offsets": [
[
0,
1523
]
]
}
] | [
{
"id": "PMID-10589785_T2",
"type": "Drug_or_compound",
"text": [
"linomide"
],
"offsets": [
[
25,
33
]
],
"normalized": []
},
{
"id": "PMID-10589785_T4",
"type": "Pathological_formation",
"text": [
"von Hippel-Lindau paraganglioma xenografts"
],
"offsets": [
[
62,
104
]
],
"normalized": []
},
{
"id": "PMID-10589785_T6",
"type": "Drug_or_compound",
"text": [
"linomide"
],
"offsets": [
[
210,
218
]
],
"normalized": []
},
{
"id": "PMID-10589785_T7",
"type": "Pathological_formation",
"text": [
"von Hippel-Lindau (VHL)-related tumors"
],
"offsets": [
[
236,
274
]
],
"normalized": []
},
{
"id": "PMID-10589785_T8",
"type": "Tissue",
"text": [
"Paraganglioma tissue fragments"
],
"offsets": [
[
276,
306
]
],
"normalized": []
},
{
"id": "PMID-10589785_T9",
"type": "Drug_or_compound",
"text": [
"linomide"
],
"offsets": [
[
577,
585
]
],
"normalized": []
},
{
"id": "PMID-10589785_T10",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
647,
652
]
],
"normalized": []
},
{
"id": "PMID-10589785_T12",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
772,
777
]
],
"normalized": []
},
{
"id": "PMID-10589785_T14",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
883,
888
]
],
"normalized": []
},
{
"id": "PMID-10589785_T15",
"type": "Drug_or_compound",
"text": [
"linomide"
],
"offsets": [
[
903,
911
]
],
"normalized": []
},
{
"id": "PMID-10589785_T17",
"type": "Multi-tissue_structure",
"text": [
"blood vessels"
],
"offsets": [
[
951,
964
]
],
"normalized": []
},
{
"id": "PMID-10589785_T18",
"type": "Pathological_formation",
"text": [
"tumors"
],
"offsets": [
[
1028,
1034
]
],
"normalized": []
},
{
"id": "PMID-10589785_T19",
"type": "Pathological_formation",
"text": [
"tumors"
],
"offsets": [
[
1141,
1147
]
],
"normalized": []
},
{
"id": "PMID-10589785_T20",
"type": "Drug_or_compound",
"text": [
"linomide"
],
"offsets": [
[
1153,
1161
]
],
"normalized": []
},
{
"id": "PMID-10589785_T22",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1263,
1268
]
],
"normalized": []
},
{
"id": "PMID-10589785_T23",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
1269,
1303
]
],
"normalized": []
},
{
"id": "PMID-10589785_T27",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1431,
1435
]
],
"normalized": []
},
{
"id": "PMID-10589785_T29",
"type": "Pathological_formation",
"text": [
"VHL tumors"
],
"offsets": [
[
1465,
1475
]
],
"normalized": []
},
{
"id": "PMID-10589785_T1000",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
108,
112
]
],
"normalized": []
},
{
"id": "PMID-10589785_T1001",
"type": "Organism",
"text": [
"patient"
],
"offsets": [
[
346,
353
]
],
"normalized": []
},
{
"id": "PMID-10589785_T1002",
"type": "Organism",
"text": [
"BALB/c nu/nu (nude) mice"
],
"offsets": [
[
385,
409
]
],
"normalized": []
},
{
"id": "PMID-10589785_T36",
"type": "Organism_substance",
"text": [
"blood"
],
"offsets": [
[
889,
894
]
],
"normalized": []
}
] | [
{
"id": "PMID-10589785_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"diminution"
],
"offsets": [
[
758,
768
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T12"
}
]
},
{
"id": "PMID-10589785_E16",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
935,
947
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T17"
}
]
},
{
"id": "PMID-10589785_E21",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduction"
],
"offsets": [
[
1250,
1259
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T23"
}
]
},
{
"id": "PMID-10589785_E24",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
1392,
1402
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_E25"
},
{
"role": "Cause",
"ref_id": "PMID-10589785_T29"
}
]
},
{
"id": "PMID-10589785_E25",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1436,
1445
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_E12"
},
{
"role": "Cause",
"ref_id": "PMID-10589785_T27"
}
]
},
{
"id": "PMID-10589785_E26",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
1421,
1430
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T27"
}
]
},
{
"id": "PMID-10589785_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
34,
42
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_E2"
},
{
"role": "Cause",
"ref_id": "PMID-10589785_T2"
}
]
},
{
"id": "PMID-10589785_E2",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
47,
53
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T4"
}
]
},
{
"id": "PMID-10589785_E3",
"type": "Planned_process",
"trigger": {
"text": [
"treatment"
],
"offsets": [
[
223,
232
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-10589785_T6"
},
{
"role": "Theme",
"ref_id": "PMID-10589785_T7"
}
]
},
{
"id": "PMID-10589785_E4",
"type": "Planned_process",
"trigger": {
"text": [
"transplanted"
],
"offsets": [
[
359,
371
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-10589785_T8"
},
{
"role": "Theme",
"ref_id": "PMID-10589785_T1002"
}
]
},
{
"id": "PMID-10589785_E5",
"type": "Planned_process",
"trigger": {
"text": [
"obtained"
],
"offsets": [
[
307,
315
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10589785_T8"
}
]
},
{
"id": "PMID-10589785_E6",
"type": "Planned_process",
"trigger": {
"text": [
"received"
],
"offsets": [
[
551,
559
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-10589785_T9"
}
]
},
{
"id": "PMID-10589785_E7",
"type": "Planned_process",
"trigger": {
"text": [
"treated"
],
"offsets": [
[
912,
919
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-10589785_T15"
}
]
},
{
"id": "PMID-10589785_E8",
"type": "Planned_process",
"trigger": {
"text": [
"treated"
],
"offsets": [
[
1162,
1169
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-10589785_T20"
}
]
},
{
"id": "PMID-10589785_E9",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
8,
18
]
]
},
"arguments": []
},
{
"id": "PMID-10589785_E10",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
190,
200
]
]
},
"arguments": []
},
{
"id": "PMID-10589785_E12",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1449,
1461
]
]
},
"arguments": []
}
] | [] | [] |
7 | PMID-12140030 | [
{
"id": "PMID-12140030__text",
"type": "abstract",
"text": [
"Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration.\n\nPURPOSE: To optimize the method of treating choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). DESIGN: Experimental study and interventional case series. METHODS: The parameters associated with locating and then photocoagulating CNV feeder vessels were identified and optimized using published data and data derived from modeling the choroidal vasculature. Based on these optimized parameters, a prototype diagnostic/treatment system was designed that captures high-speed indocyanine green (ICG) angiogram images and facilitates analysis of the images by enhancing visualization of dye movement through CNV feeder vessels (FVs). The system also permits precise aiming and delivery of 810- nm wavelength photocoagulation laser energy to target FVs on a real-time ICG angiogram image of the choroidal vasculature. Target FVs are tracked by a joy-stick controlled laser aiming beam until an intravenously-injected high-concentration ICG dye bolus is observed to enter the target vessel, at which time the laser is fired. Proof of principle of the combined diagnosis/treatment system design for performing dye-enhanced photocoagulation (DEP) in the clinical setting and determination of the minimum DEP laser energy needed to close CNV FVs was made in 11 AMD patients requiring treatment of CNV, but for whom other treatment was not appropriate. RESULTS: Using ICG-DEP, CNV feeder vessels were closed with single pulse laser energy, delivering as little as 0.6 to 1.8 J of energy to the fundus, producing no visible change in the fundus. Successful FV closure was usually indicated immediately by presence of incarcerated ICG dye in the vessel adjacent to the burn site. The prototype system proved relatively easy to operate. After acquiring and interpreting diagnostic angiograms and repositioning a patient in front of the device, feeder vessel DEP and treatment evaluation required 15 to 20 minutes. CONCLUSIONS: Indocyanine green dye-enhanced photocoagulation of CNV feeder vessels, facilitated by use of a device that permits real-time visualization of the choroidal circulation while aiming the treatment laser beam, appears to minimize the amount of energy applied to the fundus and the volume of fundus tissue affected by treatment, compared with other treatment modalities. The combination diagnosis/treatment device should be useful in optimizing FV treatment and in refining and evaluating the efficacy of DEP in future clinical trials.\n"
],
"offsets": [
[
0,
2604
]
]
}
] | [
{
"id": "PMID-12140030_T3",
"type": "Multi-tissue_structure",
"text": [
"feeder vessels"
],
"offsets": [
[
53,
67
]
],
"normalized": []
},
{
"id": "PMID-12140030_T8",
"type": "Multi-tissue_structure",
"text": [
"feeder vessels"
],
"offsets": [
[
392,
406
]
],
"normalized": []
},
{
"id": "PMID-12140030_T9",
"type": "Multi-tissue_structure",
"text": [
"choroidal vasculature"
],
"offsets": [
[
493,
514
]
],
"normalized": []
},
{
"id": "PMID-12140030_T10",
"type": "Drug_or_compound",
"text": [
"indocyanine green"
],
"offsets": [
[
631,
648
]
],
"normalized": []
},
{
"id": "PMID-12140030_T11",
"type": "Drug_or_compound",
"text": [
"ICG"
],
"offsets": [
[
650,
653
]
],
"normalized": []
},
{
"id": "PMID-12140030_T13",
"type": "Multi-tissue_structure",
"text": [
"feeder vessels"
],
"offsets": [
[
766,
780
]
],
"normalized": []
},
{
"id": "PMID-12140030_T14",
"type": "Multi-tissue_structure",
"text": [
"FVs"
],
"offsets": [
[
782,
785
]
],
"normalized": []
},
{
"id": "PMID-12140030_T15",
"type": "Multi-tissue_structure",
"text": [
"FVs"
],
"offsets": [
[
902,
905
]
],
"normalized": []
},
{
"id": "PMID-12140030_T16",
"type": "Drug_or_compound",
"text": [
"ICG"
],
"offsets": [
[
921,
924
]
],
"normalized": []
},
{
"id": "PMID-12140030_T17",
"type": "Multi-tissue_structure",
"text": [
"choroidal vasculature"
],
"offsets": [
[
948,
969
]
],
"normalized": []
},
{
"id": "PMID-12140030_T18",
"type": "Multi-tissue_structure",
"text": [
"FVs"
],
"offsets": [
[
978,
981
]
],
"normalized": []
},
{
"id": "PMID-12140030_T20",
"type": "Drug_or_compound",
"text": [
"ICG dye"
],
"offsets": [
[
1089,
1096
]
],
"normalized": []
},
{
"id": "PMID-12140030_T21",
"type": "Multi-tissue_structure",
"text": [
"vessel"
],
"offsets": [
[
1135,
1141
]
],
"normalized": []
},
{
"id": "PMID-12140030_T23",
"type": "Multi-tissue_structure",
"text": [
"FVs"
],
"offsets": [
[
1391,
1394
]
],
"normalized": []
},
{
"id": "PMID-12140030_T25",
"type": "Drug_or_compound",
"text": [
"ICG"
],
"offsets": [
[
1516,
1519
]
],
"normalized": []
},
{
"id": "PMID-12140030_T27",
"type": "Multi-tissue_structure",
"text": [
"feeder vessels"
],
"offsets": [
[
1529,
1543
]
],
"normalized": []
},
{
"id": "PMID-12140030_T29",
"type": "Multi-tissue_structure",
"text": [
"FV"
],
"offsets": [
[
1704,
1706
]
],
"normalized": []
},
{
"id": "PMID-12140030_T30",
"type": "Drug_or_compound",
"text": [
"ICG dye"
],
"offsets": [
[
1777,
1784
]
],
"normalized": []
},
{
"id": "PMID-12140030_T31",
"type": "Multi-tissue_structure",
"text": [
"vessel"
],
"offsets": [
[
1792,
1798
]
],
"normalized": []
},
{
"id": "PMID-12140030_T32",
"type": "Multi-tissue_structure",
"text": [
"feeder vessel"
],
"offsets": [
[
1989,
2002
]
],
"normalized": []
},
{
"id": "PMID-12140030_T33",
"type": "Drug_or_compound",
"text": [
"Indocyanine green dye"
],
"offsets": [
[
2072,
2093
]
],
"normalized": []
},
{
"id": "PMID-12140030_T35",
"type": "Multi-tissue_structure",
"text": [
"feeder vessels"
],
"offsets": [
[
2127,
2141
]
],
"normalized": []
},
{
"id": "PMID-12140030_T37",
"type": "Multi-tissue_structure",
"text": [
"fundus"
],
"offsets": [
[
2335,
2341
]
],
"normalized": []
},
{
"id": "PMID-12140030_T38",
"type": "Tissue",
"text": [
"fundus tissue"
],
"offsets": [
[
2360,
2373
]
],
"normalized": []
},
{
"id": "PMID-12140030_T39",
"type": "Multi-tissue_structure",
"text": [
"FV"
],
"offsets": [
[
2513,
2515
]
],
"normalized": []
},
{
"id": "PMID-12140030_T40",
"type": "Tissue",
"text": [
"macular"
],
"offsets": [
[
226,
233
]
],
"normalized": []
},
{
"id": "PMID-12140030_T41",
"type": "Tissue",
"text": [
"macular"
],
"offsets": [
[
96,
103
]
],
"normalized": []
},
{
"id": "PMID-12140030_T42",
"type": "Multi-tissue_structure",
"text": [
"fundus"
],
"offsets": [
[
1642,
1648
]
],
"normalized": []
},
{
"id": "PMID-12140030_T43",
"type": "Multi-tissue_structure",
"text": [
"fundus"
],
"offsets": [
[
1685,
1691
]
],
"normalized": []
},
{
"id": "PMID-12140030_T1004",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1414,
1422
]
],
"normalized": []
},
{
"id": "PMID-12140030_T1007",
"type": "Organism",
"text": [
"patient"
],
"offsets": [
[
1957,
1964
]
],
"normalized": []
}
] | [
{
"id": "PMID-12140030_E19",
"type": "Localization",
"trigger": {
"text": [
"observed"
],
"offsets": [
[
1106,
1114
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T20"
},
{
"role": "ToLoc",
"ref_id": "PMID-12140030_T21"
}
]
},
{
"id": "PMID-12140030_E28",
"type": "Planned_process",
"trigger": {
"text": [
"closure"
],
"offsets": [
[
1707,
1714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T29"
}
]
},
{
"id": "PMID-12140030_E1",
"type": "Breakdown",
"trigger": {
"text": [
"degeneration"
],
"offsets": [
[
104,
116
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T41"
}
]
},
{
"id": "PMID-12140030_E2",
"type": "Breakdown",
"trigger": {
"text": [
"degeneration"
],
"offsets": [
[
234,
246
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T40"
}
]
},
{
"id": "PMID-12140030_E3",
"type": "Planned_process",
"trigger": {
"text": [
"treatment"
],
"offsets": [
[
11,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_E14"
}
]
},
{
"id": "PMID-12140030_E4",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
68,
78
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_E1"
},
{
"role": "Cause",
"ref_id": "PMID-12140030_E14"
}
]
},
{
"id": "PMID-12140030_E5",
"type": "Planned_process",
"trigger": {
"text": [
"treating"
],
"offsets": [
[
154,
162
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_E15"
}
]
},
{
"id": "PMID-12140030_E6",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
198,
208
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_E2"
},
{
"role": "Cause",
"ref_id": "PMID-12140030_E15"
}
]
},
{
"id": "PMID-12140030_E7",
"type": "Planned_process",
"trigger": {
"text": [
"intravenously-injected"
],
"offsets": [
[
1047,
1069
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-12140030_T20"
}
]
},
{
"id": "PMID-12140030_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"requiring"
],
"offsets": [
[
1423,
1432
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12140030_E10"
},
{
"role": "Theme",
"ref_id": "PMID-12140030_T1004"
}
]
},
{
"id": "PMID-12140030_E10",
"type": "Planned_process",
"trigger": {
"text": [
"treatment"
],
"offsets": [
[
1433,
1442
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_E21"
}
]
},
{
"id": "PMID-12140030_E11",
"type": "Planned_process",
"trigger": {
"text": [
"closed"
],
"offsets": [
[
1549,
1555
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T27"
},
{
"role": "Instrument",
"ref_id": "PMID-12140030_T25"
}
]
},
{
"id": "PMID-12140030_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
2094,
2102
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12140030_T33"
},
{
"role": "Theme",
"ref_id": "PMID-12140030_E8"
}
]
},
{
"id": "PMID-12140030_E13",
"type": "Planned_process",
"trigger": {
"text": [
"treatment"
],
"offsets": [
[
2516,
2525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T39"
}
]
},
{
"id": "PMID-12140030_E14",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"neovascularization"
],
"offsets": [
[
34,
52
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T3"
}
]
},
{
"id": "PMID-12140030_E15",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"neovascularization"
],
"offsets": [
[
173,
191
]
]
},
"arguments": []
},
{
"id": "PMID-12140030_E16",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
193,
196
]
]
},
"arguments": []
},
{
"id": "PMID-12140030_E17",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
388,
391
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T8"
}
]
},
{
"id": "PMID-12140030_E18",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
762,
765
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T13"
}
]
},
{
"id": "PMID-12140030_E20",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
1387,
1390
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T23"
}
]
},
{
"id": "PMID-12140030_E21",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
1446,
1449
]
]
},
"arguments": []
},
{
"id": "PMID-12140030_E22",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
1525,
1528
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T27"
}
]
},
{
"id": "PMID-12140030_E23",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"CNV"
],
"offsets": [
[
2123,
2126
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T35"
}
]
},
{
"id": "PMID-12140030_E8",
"type": "Planned_process",
"trigger": {
"text": [
"photocoagulation"
],
"offsets": [
[
2103,
2119
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T35"
}
]
},
{
"id": "PMID-12140030_E24",
"type": "Planned_process",
"trigger": {
"text": [
"photocoagulating"
],
"offsets": [
[
371,
387
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12140030_T8"
}
]
}
] | [
{
"id": "PMID-12140030_1",
"entity_ids": [
"PMID-12140030_T13",
"PMID-12140030_T14"
]
},
{
"id": "PMID-12140030_2",
"entity_ids": [
"PMID-12140030_T10",
"PMID-12140030_T11"
]
}
] | [] |
8 | PMID-11238633 | [
{
"id": "PMID-11238633__text",
"type": "abstract",
"text": [
"IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk.\n\nIn vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular injury. Although in vivo studies have shown that such inhibition stems from complex interactions of immune cells and the production of IFN-gamma and other downstream angiostatic chemokines, the mechanisms involved are still poorly defined. Here we show that IL-12 activates an anti-angiogenic program in Con A-activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The soluble factors they release in its presence arrest the cycle of endothelial cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell-cell contact, yet result from continuous interaction between activated lymphoid cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10 and monokine-induced by IFN-gamma chemokines are pivotal in inducing these effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated spc enriched in specific cell subpopulations demonstrated that CD4(+), CD8(+), and NK cells are all needed to mediate the full anti-angiogenetic effect of IL-12.\n"
],
"offsets": [
[
0,
1458
]
]
}
] | [
{
"id": "PMID-11238633_T2",
"type": "Gene_or_gene_product",
"text": [
"IL-12"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "PMID-11238633_T4",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
20,
36
]
],
"normalized": []
},
{
"id": "PMID-11238633_T8",
"type": "Cell",
"text": [
"lymphocyte"
],
"offsets": [
[
75,
85
]
],
"normalized": []
},
{
"id": "PMID-11238633_T9",
"type": "Cell",
"text": [
"endothelial cell"
],
"offsets": [
[
86,
102
]
],
"normalized": []
},
{
"id": "PMID-11238633_T11",
"type": "Gene_or_gene_product",
"text": [
"IL-12"
],
"offsets": [
[
124,
129
]
],
"normalized": []
},
{
"id": "PMID-11238633_T12",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
140,
145
]
],
"normalized": []
},
{
"id": "PMID-11238633_T13",
"type": "Gene_or_gene_product",
"text": [
"IL-12"
],
"offsets": [
[
181,
186
]
],
"normalized": []
},
{
"id": "PMID-11238633_T14",
"type": "Gene_or_gene_product",
"text": [
"CD8"
],
"offsets": [
[
201,
204
]
],
"normalized": []
},
{
"id": "PMID-11238633_T19",
"type": "Cell",
"text": [
"immune cells"
],
"offsets": [
[
369,
381
]
],
"normalized": []
},
{
"id": "PMID-11238633_T21",
"type": "Gene_or_gene_product",
"text": [
"IFN-gamma"
],
"offsets": [
[
404,
413
]
],
"normalized": []
},
{
"id": "PMID-11238633_T23",
"type": "Gene_or_gene_product",
"text": [
"IL-12"
],
"offsets": [
[
527,
532
]
],
"normalized": []
},
{
"id": "PMID-11238633_T27",
"type": "Drug_or_compound",
"text": [
"Con A"
],
"offsets": [
[
573,
578
]
],
"normalized": []
},
{
"id": "PMID-11238633_T28",
"type": "Cell",
"text": [
"spleen cells"
],
"offsets": [
[
595,
607
]
],
"normalized": []
},
{
"id": "PMID-11238633_T30",
"type": "Cell",
"text": [
"spc"
],
"offsets": [
[
619,
622
]
],
"normalized": []
},
{
"id": "PMID-11238633_T31",
"type": "Cell",
"text": [
"PBMC"
],
"offsets": [
[
633,
637
]
],
"normalized": []
},
{
"id": "PMID-11238633_T33",
"type": "Cell",
"text": [
"PBMC"
],
"offsets": [
[
649,
653
]
],
"normalized": []
},
{
"id": "PMID-11238633_T35",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
725,
742
]
],
"normalized": []
},
{
"id": "PMID-11238633_T36",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
744,
746
]
],
"normalized": []
},
{
"id": "PMID-11238633_T40",
"type": "Gene_or_gene_product",
"text": [
"matrix metalloproteinase-9"
],
"offsets": [
[
818,
844
]
],
"normalized": []
},
{
"id": "PMID-11238633_T42",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
865,
867
]
],
"normalized": []
},
{
"id": "PMID-11238633_T43",
"type": "Gene_or_gene_product",
"text": [
"vitronectin"
],
"offsets": [
[
881,
892
]
],
"normalized": []
},
{
"id": "PMID-11238633_T46",
"type": "Gene_or_gene_product",
"text": [
"ICAM-1"
],
"offsets": [
[
909,
915
]
],
"normalized": []
},
{
"id": "PMID-11238633_T47",
"type": "Gene_or_gene_product",
"text": [
"VCAM-1"
],
"offsets": [
[
920,
926
]
],
"normalized": []
},
{
"id": "PMID-11238633_T48",
"type": "Cell",
"text": [
"lymphoid cells"
],
"offsets": [
[
1051,
1065
]
],
"normalized": []
},
{
"id": "PMID-11238633_T49",
"type": "Cell",
"text": [
"EC"
],
"offsets": [
[
1070,
1072
]
],
"normalized": []
},
{
"id": "PMID-11238633_T50",
"type": "Gene_or_gene_product",
"text": [
"IFN-inducible protein-10"
],
"offsets": [
[
1116,
1140
]
],
"normalized": []
},
{
"id": "PMID-11238633_T53",
"type": "Cell",
"text": [
"spc"
],
"offsets": [
[
1296,
1299
]
],
"normalized": []
},
{
"id": "PMID-11238633_T54",
"type": "Gene_or_gene_product",
"text": [
"CD4"
],
"offsets": [
[
1359,
1362
]
],
"normalized": []
},
{
"id": "PMID-11238633_T55",
"type": "Gene_or_gene_product",
"text": [
"CD8"
],
"offsets": [
[
1367,
1370
]
],
"normalized": []
},
{
"id": "PMID-11238633_T56",
"type": "Cell",
"text": [
"NK cells"
],
"offsets": [
[
1379,
1387
]
],
"normalized": []
},
{
"id": "PMID-11238633_T59",
"type": "Gene_or_gene_product",
"text": [
"IL-12"
],
"offsets": [
[
1451,
1456
]
],
"normalized": []
},
{
"id": "PMID-11238633_T1000",
"type": "Organism",
"text": [
"mouse"
],
"offsets": [
[
589,
594
]
],
"normalized": []
},
{
"id": "PMID-11238633_T1001",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
627,
632
]
],
"normalized": []
},
{
"id": "PMID-11238633_T1002",
"type": "Organism",
"text": [
"nu/nu mice"
],
"offsets": [
[
1242,
1252
]
],
"normalized": []
},
{
"id": "PMID-11238633_T1003",
"type": "Organism",
"text": [
"nonobese diabetic-SCID mice"
],
"offsets": [
[
1254,
1281
]
],
"normalized": []
},
{
"id": "PMID-11238633_T6",
"type": "Cell",
"text": [
"CD4(+)"
],
"offsets": [
[
1359,
1365
]
],
"normalized": []
},
{
"id": "PMID-11238633_T15",
"type": "Cell",
"text": [
"CD8(+)"
],
"offsets": [
[
1367,
1373
]
],
"normalized": []
},
{
"id": "PMID-11238633_T62",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
975,
979
]
],
"normalized": []
},
{
"id": "PMID-11238633_T63",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
980,
984
]
],
"normalized": []
},
{
"id": "PMID-11238633_T66",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1321,
1325
]
],
"normalized": []
}
] | [
{
"id": "PMID-11238633_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
6,
16
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T2"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T4"
}
]
},
{
"id": "PMID-11238633_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
146,
156
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T12"
}
]
},
{
"id": "PMID-11238633_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
390,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T21"
}
]
},
{
"id": "PMID-11238633_E26",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
579,
588
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T27"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T28"
}
]
},
{
"id": "PMID-11238633_E29",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
609,
618
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T30"
}
]
},
{
"id": "PMID-11238633_E32",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
639,
648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T33"
}
]
},
{
"id": "PMID-11238633_E34",
"type": "Negative_regulation",
"trigger": {
"text": [
"arrest"
],
"offsets": [
[
705,
711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T35"
}
]
},
{
"id": "PMID-11238633_E39",
"type": "Negative_regulation",
"trigger": {
"text": [
"negatively modulate"
],
"offsets": [
[
780,
799
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E11"
}
]
},
{
"id": "PMID-11238633_E41",
"type": "Binding",
"trigger": {
"text": [
"adhere"
],
"offsets": [
[
871,
877
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T42"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T43"
}
]
},
{
"id": "PMID-11238633_E44",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulate"
],
"offsets": [
[
897,
908
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E45"
}
]
},
{
"id": "PMID-11238633_E45",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
927,
937
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T47"
}
]
},
{
"id": "PMID-11238633_E52",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1286,
1295
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T53"
}
]
},
{
"id": "PMID-11238633_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
6,
16
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T2"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_E23"
}
]
},
{
"id": "PMID-11238633_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
130,
139
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T11"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_E10"
}
]
},
{
"id": "PMID-11238633_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
228,
235
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T13"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_E24"
}
]
},
{
"id": "PMID-11238633_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
533,
542
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T23"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_E7"
}
]
},
{
"id": "PMID-11238633_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"program"
],
"offsets": [
[
562,
569
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E25"
}
]
},
{
"id": "PMID-11238633_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
579,
588
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T27"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T31"
}
]
},
{
"id": "PMID-11238633_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
749,
756
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E27"
}
]
},
{
"id": "PMID-11238633_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
804,
814
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T40"
}
]
},
{
"id": "PMID-11238633_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"negatively modulate"
],
"offsets": [
[
780,
799
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E41"
}
]
},
{
"id": "PMID-11238633_E13",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
927,
937
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T46"
}
]
},
{
"id": "PMID-11238633_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulate"
],
"offsets": [
[
897,
908
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E13"
}
]
},
{
"id": "PMID-11238633_E15",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
1021,
1032
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T48"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T49"
}
]
},
{
"id": "PMID-11238633_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1041,
1050
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T48"
}
]
},
{
"id": "PMID-11238633_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1041,
1050
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T49"
}
]
},
{
"id": "PMID-11238633_E18",
"type": "Regulation",
"trigger": {
"text": [
"mediate"
],
"offsets": [
[
1406,
1413
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E19"
}
]
},
{
"id": "PMID-11238633_E19",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
1441,
1447
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-11238633_T59"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_E28"
}
]
},
{
"id": "PMID-11238633_E21",
"type": "Binding",
"trigger": {
"text": [
"contact"
],
"offsets": [
[
985,
992
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_T63"
},
{
"role": "Theme",
"ref_id": "PMID-11238633_T62"
}
]
},
{
"id": "PMID-11238633_E22",
"type": "Regulation",
"trigger": {
"text": [
"require"
],
"offsets": [
[
960,
967
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-11238633_E21"
}
]
},
{
"id": "PMID-11238633_E23",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
51,
63
]
]
},
"arguments": []
},
{
"id": "PMID-11238633_E24",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
236,
248
]
]
},
"arguments": []
},
{
"id": "PMID-11238633_E25",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
551,
561
]
]
},
"arguments": []
},
{
"id": "PMID-11238633_E27",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
766,
778
]
]
},
"arguments": []
},
{
"id": "PMID-11238633_E28",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenetic"
],
"offsets": [
[
1428,
1440
]
]
},
"arguments": []
}
] | [
{
"id": "PMID-11238633_1",
"entity_ids": [
"PMID-11238633_T35",
"PMID-11238633_T36"
]
},
{
"id": "PMID-11238633_2",
"entity_ids": [
"PMID-11238633_T30",
"PMID-11238633_T28"
]
},
{
"id": "PMID-11238633_3",
"entity_ids": [
"PMID-11238633_T33",
"PMID-11238633_T31"
]
}
] | [
{
"id": "PMID-11238633_R1",
"type": "frag",
"arg1_id": "PMID-11238633_T15",
"arg2_id": "PMID-11238633_T56",
"normalized": []
},
{
"id": "PMID-11238633_R2",
"type": "frag",
"arg1_id": "PMID-11238633_T6",
"arg2_id": "PMID-11238633_T56",
"normalized": []
}
] |
9 | PMID-16310808 | [
{
"id": "PMID-16310808__text",
"type": "abstract",
"text": [
"Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.\n\nAngiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.\n"
],
"offsets": [
[
0,
1660
]
]
}
] | [
{
"id": "PMID-16310808_T1",
"type": "Drug_or_compound",
"text": [
"thalidomide"
],
"offsets": [
[
10,
21
]
],
"normalized": []
},
{
"id": "PMID-16310808_T4",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
32,
36
]
],
"normalized": []
},
{
"id": "PMID-16310808_T11",
"type": "Tissue",
"text": [
"capillary tube"
],
"offsets": [
[
77,
91
]
],
"normalized": []
},
{
"id": "PMID-16310808_T12",
"type": "Cell",
"text": [
"endothelial EA.hy 926 cells"
],
"offsets": [
[
111,
138
]
],
"normalized": []
},
{
"id": "PMID-16310808_T15",
"type": "Multi-tissue_structure",
"text": [
"blood vessel"
],
"offsets": [
[
159,
171
]
],
"normalized": []
},
{
"id": "PMID-16310808_T23",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
272,
289
]
],
"normalized": []
},
{
"id": "PMID-16310808_T24",
"type": "Tissue",
"text": [
"capillary microvessels"
],
"offsets": [
[
344,
366
]
],
"normalized": []
},
{
"id": "PMID-16310808_T26",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
378,
386
]
],
"normalized": []
},
{
"id": "PMID-16310808_T28",
"type": "Multi-tissue_structure",
"text": [
"blood vessel"
],
"offsets": [
[
403,
415
]
],
"normalized": []
},
{
"id": "PMID-16310808_T30",
"type": "Pathological_formation",
"text": [
"solid tumors"
],
"offsets": [
[
496,
508
]
],
"normalized": []
},
{
"id": "PMID-16310808_T31",
"type": "Drug_or_compound",
"text": [
"Thalidomide"
],
"offsets": [
[
520,
531
]
],
"normalized": []
},
{
"id": "PMID-16310808_T32",
"type": "Drug_or_compound",
"text": [
"alpha-(N-phthalimido)-glutarimide"
],
"offsets": [
[
533,
566
]
],
"normalized": []
},
{
"id": "PMID-16310808_T36",
"type": "Drug_or_compound",
"text": [
"thalidomide"
],
"offsets": [
[
746,
757
]
],
"normalized": []
},
{
"id": "PMID-16310808_T38",
"type": "Drug_or_compound",
"text": [
"thalidomide"
],
"offsets": [
[
851,
862
]
],
"normalized": []
},
{
"id": "PMID-16310808_T40",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
866,
870
]
],
"normalized": []
},
{
"id": "PMID-16310808_T46",
"type": "Tissue",
"text": [
"capillary"
],
"offsets": [
[
921,
930
]
],
"normalized": []
},
{
"id": "PMID-16310808_T47",
"type": "Cell",
"text": [
"endothelial cell line EA.hy 926"
],
"offsets": [
[
950,
981
]
],
"normalized": []
},
{
"id": "PMID-16310808_T48",
"type": "Drug_or_compound",
"text": [
"Thalidomide"
],
"offsets": [
[
983,
994
]
],
"normalized": []
},
{
"id": "PMID-16310808_T50",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1056,
1060
]
],
"normalized": []
},
{
"id": "PMID-16310808_T52",
"type": "Tissue",
"text": [
"capillary tubes"
],
"offsets": [
[
1121,
1136
]
],
"normalized": []
},
{
"id": "PMID-16310808_T53",
"type": "Gene_or_gene_product",
"text": [
"collagen"
],
"offsets": [
[
1168,
1176
]
],
"normalized": []
},
{
"id": "PMID-16310808_T55",
"type": "Drug_or_compound",
"text": [
"thalidomide"
],
"offsets": [
[
1196,
1207
]
],
"normalized": []
},
{
"id": "PMID-16310808_T62",
"type": "Drug_or_compound",
"text": [
"Thalidomide"
],
"offsets": [
[
1319,
1330
]
],
"normalized": []
},
{
"id": "PMID-16310808_T67",
"type": "Drug_or_compound",
"text": [
"thalidomide"
],
"offsets": [
[
1478,
1489
]
],
"normalized": []
},
{
"id": "PMID-16310808_T71",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1528,
1532
]
],
"normalized": []
},
{
"id": "PMID-16310808_T74",
"type": "Tissue",
"text": [
"capillary microvessel"
],
"offsets": [
[
1547,
1568
]
],
"normalized": []
},
{
"id": "PMID-16310808_T79",
"type": "Cell",
"text": [
"EA.hy 926 cells"
],
"offsets": [
[
1620,
1635
]
],
"normalized": []
},
{
"id": "PMID-16310808_T1000",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
105,
110
]
],
"normalized": []
},
{
"id": "PMID-16310808_T1001",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
944,
949
]
],
"normalized": []
},
{
"id": "PMID-16310808_T84",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1151,
1155
]
],
"normalized": []
},
{
"id": "PMID-16310808_T85",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1393,
1397
]
],
"normalized": []
},
{
"id": "PMID-16310808_T88",
"type": "Cell",
"text": [
"cell cultures"
],
"offsets": [
[
1420,
1433
]
],
"normalized": []
},
{
"id": "PMID-16310808_T5",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1254,
1258
]
],
"normalized": []
},
{
"id": "PMID-16310808_T16",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1303,
1307
]
],
"normalized": []
}
] | [
{
"id": "PMID-16310808_E3",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
37,
46
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T4"
}
]
},
{
"id": "PMID-16310808_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1046,
1055
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E49"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_T48"
}
]
},
{
"id": "PMID-16310808_E10",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
92,
101
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T11"
}
]
},
{
"id": "PMID-16310808_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
262,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E22"
}
]
},
{
"id": "PMID-16310808_E22",
"type": "Localization",
"trigger": {
"text": [
"migrate"
],
"offsets": [
[
293,
300
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T23"
}
]
},
{
"id": "PMID-16310808_E39",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
871,
880
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T40"
}
]
},
{
"id": "PMID-16310808_E49",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
1061,
1070
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T50"
}
]
},
{
"id": "PMID-16310808_E69",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory action"
],
"offsets": [
[
1507,
1524
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E70"
}
]
},
{
"id": "PMID-16310808_E70",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
1533,
1542
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T71"
}
]
},
{
"id": "PMID-16310808_E72",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
1569,
1578
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T74"
}
]
},
{
"id": "PMID-16310808_E76",
"type": "Binding",
"trigger": {
"text": [
"adhesion"
],
"offsets": [
[
1650,
1658
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T79"
}
]
},
{
"id": "PMID-16310808_E78",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1636,
1645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T79"
}
]
},
{
"id": "PMID-16310808_E13",
"type": "Regulation",
"trigger": {
"text": [
"affecting"
],
"offsets": [
[
22,
31
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T1"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E3"
}
]
},
{
"id": "PMID-16310808_E6",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
172,
181
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T15"
}
]
},
{
"id": "PMID-16310808_E8",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
217,
226
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E58"
}
]
},
{
"id": "PMID-16310808_E15",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferate"
],
"offsets": [
[
302,
313
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T23"
}
]
},
{
"id": "PMID-16310808_E16",
"type": "Development",
"trigger": {
"text": [
"differentiate"
],
"offsets": [
[
318,
331
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T23"
}
]
},
{
"id": "PMID-16310808_E17",
"type": "Development",
"trigger": {
"text": [
"form"
],
"offsets": [
[
335,
339
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T24"
}
]
},
{
"id": "PMID-16310808_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
262,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E15"
}
]
},
{
"id": "PMID-16310808_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulate"
],
"offsets": [
[
262,
271
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E16"
}
]
},
{
"id": "PMID-16310808_E23",
"type": "Regulation",
"trigger": {
"text": [
"affecting"
],
"offsets": [
[
22,
31
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T1"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E63"
}
]
},
{
"id": "PMID-16310808_E24",
"type": "Regulation",
"trigger": {
"text": [
"affecting"
],
"offsets": [
[
22,
31
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T1"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E1"
}
]
},
{
"id": "PMID-16310808_E26",
"type": "Regulation",
"trigger": {
"text": [
"affecting"
],
"offsets": [
[
22,
31
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T1"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E10"
}
]
},
{
"id": "PMID-16310808_E28",
"type": "Development",
"trigger": {
"text": [
"development"
],
"offsets": [
[
387,
398
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T26"
}
]
},
{
"id": "PMID-16310808_E29",
"type": "Remodeling",
"trigger": {
"text": [
"remodeling"
],
"offsets": [
[
416,
426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T28"
}
]
},
{
"id": "PMID-16310808_E30",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
509,
518
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T30"
}
]
},
{
"id": "PMID-16310808_E31",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory action"
],
"offsets": [
[
644,
661
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E60"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_T31"
}
]
},
{
"id": "PMID-16310808_E32",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
733,
742
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T36"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E61"
}
]
},
{
"id": "PMID-16310808_E33",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
841,
847
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T38"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E39"
}
]
},
{
"id": "PMID-16310808_E34",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
931,
940
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T46"
}
]
},
{
"id": "PMID-16310808_E35",
"type": "Localization",
"trigger": {
"text": [
"cell migration"
],
"offsets": [
[
882,
896
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T47"
}
]
},
{
"id": "PMID-16310808_E36",
"type": "Binding",
"trigger": {
"text": [
"adhesion"
],
"offsets": [
[
898,
906
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T47"
}
]
},
{
"id": "PMID-16310808_E37",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
841,
847
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T38"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E34"
}
]
},
{
"id": "PMID-16310808_E38",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
841,
847
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T38"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E36"
}
]
},
{
"id": "PMID-16310808_E40",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
841,
847
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T38"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E35"
}
]
},
{
"id": "PMID-16310808_E41",
"type": "Development",
"trigger": {
"text": [
"formed"
],
"offsets": [
[
1114,
1120
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T52"
}
]
},
{
"id": "PMID-16310808_E42",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1090,
1099
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T48"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E41"
}
]
},
{
"id": "PMID-16310808_E43",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1141,
1150
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E44"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_T48"
}
]
},
{
"id": "PMID-16310808_E44",
"type": "Binding",
"trigger": {
"text": [
"adhesion"
],
"offsets": [
[
1156,
1164
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T53"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_T84"
}
]
},
{
"id": "PMID-16310808_E46",
"type": "Planned_process",
"trigger": {
"text": [
"Administration"
],
"offsets": [
[
1178,
1192
]
]
},
"arguments": [
{
"role": "Instrument",
"ref_id": "PMID-16310808_T55"
}
]
},
{
"id": "PMID-16310808_E47",
"type": "Negative_regulation",
"trigger": {
"text": [
"action"
],
"offsets": [
[
1468,
1474
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E62"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_T67"
}
]
},
{
"id": "PMID-16310808_E48",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
1493,
1496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E47"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_E69"
}
]
},
{
"id": "PMID-16310808_E50",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory action"
],
"offsets": [
[
1507,
1524
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E72"
}
]
},
{
"id": "PMID-16310808_E52",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
1493,
1496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E47"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_E50"
}
]
},
{
"id": "PMID-16310808_E53",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
1607,
1616
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T67"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E78"
}
]
},
{
"id": "PMID-16310808_E54",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
1607,
1616
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T67"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E76"
}
]
},
{
"id": "PMID-16310808_E55",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
1398,
1411
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T85"
}
]
},
{
"id": "PMID-16310808_E56",
"type": "Regulation",
"trigger": {
"text": [
"change"
],
"offsets": [
[
1386,
1392
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16310808_T62"
},
{
"role": "Theme",
"ref_id": "PMID-16310808_E55"
}
]
},
{
"id": "PMID-16310808_E58",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
141,
153
]
]
},
"arguments": []
},
{
"id": "PMID-16310808_E59",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
234,
244
]
]
},
"arguments": []
},
{
"id": "PMID-16310808_E60",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
605,
617
]
]
},
"arguments": []
},
{
"id": "PMID-16310808_E61",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
782,
794
]
]
},
"arguments": []
},
{
"id": "PMID-16310808_E62",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1457,
1467
]
]
},
"arguments": []
},
{
"id": "PMID-16310808_E63",
"type": "Localization",
"trigger": {
"text": [
"cell migration"
],
"offsets": [
[
48,
62
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T12"
}
]
},
{
"id": "PMID-16310808_E1",
"type": "Binding",
"trigger": {
"text": [
"adhesion"
],
"offsets": [
[
64,
72
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T12"
}
]
},
{
"id": "PMID-16310808_E2",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1259,
1268
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T5"
}
]
},
{
"id": "PMID-16310808_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
1244,
1253
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E2"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_E46"
}
]
},
{
"id": "PMID-16310808_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1293,
1302
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_E9"
},
{
"role": "Cause",
"ref_id": "PMID-16310808_E46"
}
]
},
{
"id": "PMID-16310808_E9",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1308,
1317
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16310808_T16"
}
]
}
] | [
{
"id": "PMID-16310808_1",
"entity_ids": [
"PMID-16310808_T31",
"PMID-16310808_T32"
]
}
] | [] |
10 | PMID-15725689 | [
{
"id": "PMID-15725689__text",
"type": "abstract",
"text": [
"Role of thrombogenic factors in the development of atherosclerosis.\n\nHemostatic factors play a crucial role in generating thrombotic plugs at sites of vascular damage (atherothrombosis). However, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis remains uncertain. Autopsy studies have revealed that intimal thickening represents the first stage of atherosclerosis and that lipid-rich plaque arises from such lesions. Several factors contribute to the start of intimal thickening. Platelets release several growth factors and bioactive agents that play a central role in development of not only thrombus but also of intimal thickening. We have been investigating which coagulation factors simultaneously, or subsequently with platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an essential initiator of blood coagulation that is expressed in various stages of atherosclerotic lesions in humans and other animals. Factors including thrombin and fibrin, which are downstream of the coagulation cascade activated by TF, also contribute to atherosclerosis. TF is involved in cell migration, embryogenesis and angiogenesis. Thus TF, in addition to factors downstream of the coagulation cascade and the protease-activated receptor 2 activation system, would be a multifactorial regulator of atherogenesis.\n"
],
"offsets": [
[
0,
1378
]
]
}
] | [
{
"id": "PMID-15725689_T1",
"type": "Gene_or_gene_product",
"text": [
"thrombogenic factors"
],
"offsets": [
[
8,
28
]
],
"normalized": []
},
{
"id": "PMID-15725689_T2",
"type": "Gene_or_gene_product",
"text": [
"Hemostatic factors"
],
"offsets": [
[
69,
87
]
],
"normalized": []
},
{
"id": "PMID-15725689_T3",
"type": "Gene_or_gene_product",
"text": [
"hemostatic factors"
],
"offsets": [
[
204,
222
]
],
"normalized": []
},
{
"id": "PMID-15725689_T4",
"type": "Tissue",
"text": [
"intimal"
],
"offsets": [
[
350,
357
]
],
"normalized": []
},
{
"id": "PMID-15725689_T5",
"type": "Tissue",
"text": [
"intimal"
],
"offsets": [
[
511,
518
]
],
"normalized": []
},
{
"id": "PMID-15725689_T6",
"type": "Cell",
"text": [
"Platelets"
],
"offsets": [
[
531,
540
]
],
"normalized": []
},
{
"id": "PMID-15725689_T7",
"type": "Tissue",
"text": [
"intimal"
],
"offsets": [
[
666,
673
]
],
"normalized": []
},
{
"id": "PMID-15725689_T8",
"type": "Cell",
"text": [
"platelet"
],
"offsets": [
[
776,
784
]
],
"normalized": []
},
{
"id": "PMID-15725689_T9",
"type": "Gene_or_gene_product",
"text": [
"Tissue factor"
],
"offsets": [
[
833,
846
]
],
"normalized": []
},
{
"id": "PMID-15725689_T10",
"type": "Gene_or_gene_product",
"text": [
"TF"
],
"offsets": [
[
848,
850
]
],
"normalized": []
},
{
"id": "PMID-15725689_T11",
"type": "Organism_substance",
"text": [
"blood"
],
"offsets": [
[
881,
886
]
],
"normalized": []
},
{
"id": "PMID-15725689_T12",
"type": "Gene_or_gene_product",
"text": [
"thrombin"
],
"offsets": [
[
1009,
1017
]
],
"normalized": []
},
{
"id": "PMID-15725689_T13",
"type": "Gene_or_gene_product",
"text": [
"fibrin"
],
"offsets": [
[
1022,
1028
]
],
"normalized": []
},
{
"id": "PMID-15725689_T16",
"type": "Gene_or_gene_product",
"text": [
"TF"
],
"offsets": [
[
1091,
1093
]
],
"normalized": []
},
{
"id": "PMID-15725689_T17",
"type": "Gene_or_gene_product",
"text": [
"TF"
],
"offsets": [
[
1131,
1133
]
],
"normalized": []
},
{
"id": "PMID-15725689_T20",
"type": "Gene_or_gene_product",
"text": [
"TF"
],
"offsets": [
[
1202,
1204
]
],
"normalized": []
},
{
"id": "PMID-15725689_T23",
"type": "Gene_or_gene_product",
"text": [
"protease-activated receptor 2"
],
"offsets": [
[
1275,
1304
]
],
"normalized": []
},
{
"id": "PMID-15725689_T1000",
"type": "Organism",
"text": [
"humans"
],
"offsets": [
[
965,
971
]
],
"normalized": []
},
{
"id": "PMID-15725689_T28",
"type": "Multi-tissue_structure",
"text": [
"vascular"
],
"offsets": [
[
151,
159
]
],
"normalized": []
},
{
"id": "PMID-15725689_T24",
"type": "Pathological_formation",
"text": [
"thrombotic plugs"
],
"offsets": [
[
122,
138
]
],
"normalized": []
},
{
"id": "PMID-15725689_T33",
"type": "Pathological_formation",
"text": [
"lipid-rich plaque"
],
"offsets": [
[
424,
441
]
],
"normalized": []
},
{
"id": "PMID-15725689_T34",
"type": "Pathological_formation",
"text": [
"thrombus"
],
"offsets": [
[
645,
653
]
],
"normalized": []
},
{
"id": "PMID-15725689_T35",
"type": "Pathological_formation",
"text": [
"thrombus"
],
"offsets": [
[
813,
821
]
],
"normalized": []
},
{
"id": "PMID-15725689_T38",
"type": "Pathological_formation",
"text": [
"atherosclerotic lesions"
],
"offsets": [
[
938,
961
]
],
"normalized": []
},
{
"id": "PMID-15725689_T41",
"type": "Pathological_formation",
"text": [
"lesions"
],
"offsets": [
[
459,
466
]
],
"normalized": []
},
{
"id": "PMID-15725689_T45",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
1149,
1153
]
],
"normalized": []
}
] | [
{
"id": "PMID-15725689_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1078,
1087
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_T16"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_E22"
}
]
},
{
"id": "PMID-15725689_E1",
"type": "Binding",
"trigger": {
"text": [
"aggregation"
],
"offsets": [
[
785,
796
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T8"
}
]
},
{
"id": "PMID-15725689_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
907,
916
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T9"
}
]
},
{
"id": "PMID-15725689_E4",
"type": "Regulation",
"trigger": {
"text": [
"downstream"
],
"offsets": [
[
1040,
1050
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_E22"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_T13"
}
]
},
{
"id": "PMID-15725689_E5",
"type": "Regulation",
"trigger": {
"text": [
"downstream"
],
"offsets": [
[
1040,
1050
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_E22"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_T12"
}
]
},
{
"id": "PMID-15725689_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
1137,
1145
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_T17"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_E21"
}
]
},
{
"id": "PMID-15725689_E7",
"type": "Breakdown",
"trigger": {
"text": [
"damage"
],
"offsets": [
[
160,
166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T28"
}
]
},
{
"id": "PMID-15725689_E8",
"type": "Growth",
"trigger": {
"text": [
"thickening"
],
"offsets": [
[
358,
368
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T4"
}
]
},
{
"id": "PMID-15725689_E9",
"type": "Growth",
"trigger": {
"text": [
"thickening"
],
"offsets": [
[
519,
529
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T5"
}
]
},
{
"id": "PMID-15725689_E10",
"type": "Growth",
"trigger": {
"text": [
"thickening"
],
"offsets": [
[
674,
684
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T7"
}
]
},
{
"id": "PMID-15725689_E2",
"type": "Development",
"trigger": {
"text": [
"formation"
],
"offsets": [
[
822,
831
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T35"
}
]
},
{
"id": "PMID-15725689_E11",
"type": "Development",
"trigger": {
"text": [
"development"
],
"offsets": [
[
621,
632
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T34"
}
]
},
{
"id": "PMID-15725689_E12",
"type": "Development",
"trigger": {
"text": [
"generating"
],
"offsets": [
[
111,
121
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T24"
}
]
},
{
"id": "PMID-15725689_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a crucial role"
],
"offsets": [
[
88,
107
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_T2"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_E12"
}
]
},
{
"id": "PMID-15725689_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"contribute"
],
"offsets": [
[
484,
494
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_E9"
}
]
},
{
"id": "PMID-15725689_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a central role"
],
"offsets": [
[
598,
617
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_E11"
}
]
},
{
"id": "PMID-15725689_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"play a central role"
],
"offsets": [
[
598,
617
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_E10"
}
]
},
{
"id": "PMID-15725689_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"participate"
],
"offsets": [
[
798,
809
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_E2"
}
]
},
{
"id": "PMID-15725689_E19",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
1154,
1163
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-15725689_T45"
}
]
},
{
"id": "PMID-15725689_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
1137,
1145
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-15725689_T17"
},
{
"role": "Theme",
"ref_id": "PMID-15725689_E19"
}
]
},
{
"id": "PMID-15725689_E21",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1183,
1195
]
]
},
"arguments": []
},
{
"id": "PMID-15725689_E22",
"type": "Pathway",
"trigger": {
"text": [
"coagulation cascade"
],
"offsets": [
[
1058,
1077
]
]
},
"arguments": []
},
{
"id": "PMID-15725689_E23",
"type": "Pathway",
"trigger": {
"text": [
"coagulation cascade"
],
"offsets": [
[
1247,
1266
]
]
},
"arguments": []
},
{
"id": "PMID-15725689_E24",
"type": "Pathway",
"trigger": {
"text": [
"activation system"
],
"offsets": [
[
1305,
1322
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-15725689_T23"
}
]
}
] | [
{
"id": "PMID-15725689_1",
"entity_ids": [
"PMID-15725689_T9",
"PMID-15725689_T10"
]
}
] | [] |
11 | PMID-10771470 | [
{
"id": "PMID-10771470__text",
"type": "abstract",
"text": [
"Active hair growth (anagen) is associated with angiogenesis.\n\nAfter the completion of skin development, angiogenesis, i.e., the growth of new capillaries from pre-existing blood vessels, is held to occur in the skin only under pathologic conditions. It has long been noted, however, that hair follicle cycling is associated with prominent changes in skin perfusion, that the epithelial hair bulbs of anagen follicles display angiogenic properties, and that the follicular dermal papilla can produce angiogenic factors. Despite these suggestive observations, no formal proof is as yet available for the concept that angiogenesis is a physiologic event that occurs all over the mature mammalian integument whenever hair follicles switch from resting (telogen) to active growth (anagen). This study uses quantitative histomorphometry and double-immunohistologic detection techniques for the demarcation of proliferating endothelial cells, to show that synchronized hair follicle cycling in adolescent C57BL/6 mice is associated with substantial angiogenesis, and that inhibiting angiogenesis in vivo by the intraperitoneal application of a fumagillin derivative retards experimentally induced anagen development in these mice. Thus, angiogenesis is a physiologic event in normal postnatal murine skin, apparently is dictated by the hair follicle, and appears to be required for normal anagen development. Anagen-associated angiogenesis offers an attractive model for identifying the physiologic controls of cutaneous angiogenesis, and an interesting system for screening the effects of potential antiangiogenic drugs in vivo.\n"
],
"offsets": [
[
0,
1623
]
]
}
] | [
{
"id": "PMID-10771470_T2",
"type": "Multi-tissue_structure",
"text": [
"hair"
],
"offsets": [
[
7,
11
]
],
"normalized": []
},
{
"id": "PMID-10771470_T3",
"type": "Tissue",
"text": [
"capillaries"
],
"offsets": [
[
142,
153
]
],
"normalized": []
},
{
"id": "PMID-10771470_T6",
"type": "Organ",
"text": [
"skin"
],
"offsets": [
[
86,
90
]
],
"normalized": []
},
{
"id": "PMID-10771470_T10",
"type": "Multi-tissue_structure",
"text": [
"blood vessels"
],
"offsets": [
[
172,
185
]
],
"normalized": []
},
{
"id": "PMID-10771470_T12",
"type": "Organ",
"text": [
"skin"
],
"offsets": [
[
211,
215
]
],
"normalized": []
},
{
"id": "PMID-10771470_T14",
"type": "Multi-tissue_structure",
"text": [
"hair follicle"
],
"offsets": [
[
288,
301
]
],
"normalized": []
},
{
"id": "PMID-10771470_T16",
"type": "Organ",
"text": [
"skin"
],
"offsets": [
[
350,
354
]
],
"normalized": []
},
{
"id": "PMID-10771470_T17",
"type": "Tissue",
"text": [
"epithelial hair bulbs"
],
"offsets": [
[
375,
396
]
],
"normalized": []
},
{
"id": "PMID-10771470_T18",
"type": "Multi-tissue_structure",
"text": [
"anagen follicles"
],
"offsets": [
[
400,
416
]
],
"normalized": []
},
{
"id": "PMID-10771470_T20",
"type": "Tissue",
"text": [
"follicular dermal papilla"
],
"offsets": [
[
461,
486
]
],
"normalized": []
},
{
"id": "PMID-10771470_T24",
"type": "Multi-tissue_structure",
"text": [
"hair follicles"
],
"offsets": [
[
713,
727
]
],
"normalized": []
},
{
"id": "PMID-10771470_T27",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
917,
934
]
],
"normalized": []
},
{
"id": "PMID-10771470_T29",
"type": "Multi-tissue_structure",
"text": [
"hair follicle"
],
"offsets": [
[
962,
975
]
],
"normalized": []
},
{
"id": "PMID-10771470_T33",
"type": "Drug_or_compound",
"text": [
"fumagillin derivative"
],
"offsets": [
[
1137,
1158
]
],
"normalized": []
},
{
"id": "PMID-10771470_T36",
"type": "Organ",
"text": [
"skin"
],
"offsets": [
[
1293,
1297
]
],
"normalized": []
},
{
"id": "PMID-10771470_T37",
"type": "Multi-tissue_structure",
"text": [
"hair follicle"
],
"offsets": [
[
1329,
1342
]
],
"normalized": []
},
{
"id": "PMID-10771470_T1000",
"type": "Organism",
"text": [
"C57BL/6 mice"
],
"offsets": [
[
998,
1010
]
],
"normalized": []
},
{
"id": "PMID-10771470_T1001",
"type": "Organism",
"text": [
"mice"
],
"offsets": [
[
1218,
1222
]
],
"normalized": []
},
{
"id": "PMID-10771470_T1002",
"type": "Organism",
"text": [
"murine"
],
"offsets": [
[
1286,
1292
]
],
"normalized": []
}
] | [
{
"id": "PMID-10771470_E1",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
12,
18
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T2"
}
]
},
{
"id": "PMID-10771470_E5",
"type": "Development",
"trigger": {
"text": [
"development"
],
"offsets": [
[
91,
102
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T6"
}
]
},
{
"id": "PMID-10771470_E9",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
128,
134
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T3"
}
]
},
{
"id": "PMID-10771470_E13",
"type": "Development",
"trigger": {
"text": [
"cycling"
],
"offsets": [
[
302,
309
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T14"
}
]
},
{
"id": "PMID-10771470_E26",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferating"
],
"offsets": [
[
903,
916
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T27"
}
]
},
{
"id": "PMID-10771470_E28",
"type": "Development",
"trigger": {
"text": [
"cycling"
],
"offsets": [
[
976,
983
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T29"
}
]
},
{
"id": "PMID-10771470_E2",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
31,
41
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10771470_E1"
},
{
"role": "Theme",
"ref_id": "PMID-10771470_E12"
}
]
},
{
"id": "PMID-10771470_E3",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
313,
323
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_E13"
}
]
},
{
"id": "PMID-10771470_E4",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
768,
774
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T24"
}
]
},
{
"id": "PMID-10771470_E6",
"type": "Growth",
"trigger": {
"text": [
"resting"
],
"offsets": [
[
740,
747
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_T24"
}
]
},
{
"id": "PMID-10771470_E7",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
1014,
1024
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10771470_E28"
},
{
"role": "Theme",
"ref_id": "PMID-10771470_E19"
}
]
},
{
"id": "PMID-10771470_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibiting"
],
"offsets": [
[
1065,
1075
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_E20"
},
{
"role": "Cause",
"ref_id": "PMID-10771470_E28"
}
]
},
{
"id": "PMID-10771470_E11",
"type": "Regulation",
"trigger": {
"text": [
"associated"
],
"offsets": [
[
1409,
1419
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10771470_E22"
}
]
},
{
"id": "PMID-10771470_E12",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
47,
59
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E14",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
104,
116
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-10771470_T12"
}
]
},
{
"id": "PMID-10771470_E16",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
425,
435
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-10771470_T17"
}
]
},
{
"id": "PMID-10771470_E17",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
499,
509
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E18",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
615,
627
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E19",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1042,
1054
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E20",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1076,
1088
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E21",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1230,
1242
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-10771470_T37"
}
]
},
{
"id": "PMID-10771470_E22",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1420,
1432
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E23",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1514,
1526
]
]
},
"arguments": []
},
{
"id": "PMID-10771470_E24",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1597,
1607
]
]
},
"arguments": []
}
] | [] | [] |
12 | PMID-18835936 | [
{
"id": "PMID-18835936__text",
"type": "abstract",
"text": [
"Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity.\n\nOBJECTIVE: The expansion of adipose tissue is linked to the development of its vasculature. However, the regulation of adipose tissue angiogenesis in humans has not been extensively studied. Our aim was to compare the angiogenesis associated with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from the same obese patients in an in vivo model. RESEARCH DESIGN AND METHODS: Adipose tissue samples from visceral (VAT) and subcutaneous (SAT) sites, obtained from 36 obese patients (mean BMI 46.5 kg/m(2)) during bariatric surgery, were layered on chick chorioallantoic membrane (CAM). RESULTS: Both SAT and VAT expressed angiogenic factors without significant difference for vascular endothelial growth factor (VEGF) expression. Adipose tissue layered on CAM stimulated angiogenesis. Angiogenic stimulation was macroscopically detectable, with engulfment of the samples, in 39% and was evidenced by angiography in 59% of the samples. A connection between CAM and adipose tissue vessels was evidenced by immunohistochemistry, with recruitment of both avian and human endothelial cells. The angiogenic potency of adipose tissue was not related to its localization (with an angiogenic stimulation in 60% of SAT samples and 61% of VAT samples) or to adipocyte size or inflammatory infiltrate assessed in adipose samples before the graft on CAM. Stimulation of angiogenesis by adipose tissue was nearly abolished by bevacizumab, which specifically targets human VEGF. CONCLUSIONS: We have established a model to study the regulation of angiogenesis by human adipose tissue. This model highlighted the role of VEGF in angiogenesis in both SAT and VAT.\n"
],
"offsets": [
[
0,
1760
]
]
}
] | [
{
"id": "PMID-18835936_T2",
"type": "Tissue",
"text": [
"visceral"
],
"offsets": [
[
29,
37
]
],
"normalized": []
},
{
"id": "PMID-18835936_T3",
"type": "Tissue",
"text": [
"subcutaneous adipose tissue"
],
"offsets": [
[
42,
69
]
],
"normalized": []
},
{
"id": "PMID-18835936_T4",
"type": "Tissue",
"text": [
"adipose tissue"
],
"offsets": [
[
124,
138
]
],
"normalized": []
},
{
"id": "PMID-18835936_T5",
"type": "Multi-tissue_structure",
"text": [
"vasculature"
],
"offsets": [
[
175,
186
]
],
"normalized": []
},
{
"id": "PMID-18835936_T6",
"type": "Tissue",
"text": [
"adipose tissue"
],
"offsets": [
[
215,
229
]
],
"normalized": []
},
{
"id": "PMID-18835936_T9",
"type": "Tissue",
"text": [
"subcutaneous adipose tissue"
],
"offsets": [
[
343,
370
]
],
"normalized": []
},
{
"id": "PMID-18835936_T10",
"type": "Tissue",
"text": [
"SAT"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "PMID-18835936_T11",
"type": "Tissue",
"text": [
"visceral adipose tissue"
],
"offsets": [
[
381,
404
]
],
"normalized": []
},
{
"id": "PMID-18835936_T12",
"type": "Tissue",
"text": [
"VAT"
],
"offsets": [
[
406,
409
]
],
"normalized": []
},
{
"id": "PMID-18835936_T13",
"type": "Tissue",
"text": [
"Adipose tissue samples"
],
"offsets": [
[
490,
512
]
],
"normalized": []
},
{
"id": "PMID-18835936_T14",
"type": "Tissue",
"text": [
"VAT"
],
"offsets": [
[
528,
531
]
],
"normalized": []
},
{
"id": "PMID-18835936_T15",
"type": "Tissue",
"text": [
"SAT"
],
"offsets": [
[
551,
554
]
],
"normalized": []
},
{
"id": "PMID-18835936_T16",
"type": "Multi-tissue_structure",
"text": [
"chorioallantoic membrane"
],
"offsets": [
[
667,
691
]
],
"normalized": []
},
{
"id": "PMID-18835936_T17",
"type": "Multi-tissue_structure",
"text": [
"CAM"
],
"offsets": [
[
693,
696
]
],
"normalized": []
},
{
"id": "PMID-18835936_T19",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
789,
823
]
],
"normalized": []
},
{
"id": "PMID-18835936_T20",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
825,
829
]
],
"normalized": []
},
{
"id": "PMID-18835936_T21",
"type": "Multi-tissue_structure",
"text": [
"CAM"
],
"offsets": [
[
869,
872
]
],
"normalized": []
},
{
"id": "PMID-18835936_T24",
"type": "Multi-tissue_structure",
"text": [
"CAM"
],
"offsets": [
[
1069,
1072
]
],
"normalized": []
},
{
"id": "PMID-18835936_T25",
"type": "Tissue",
"text": [
"adipose tissue vessels"
],
"offsets": [
[
1077,
1099
]
],
"normalized": []
},
{
"id": "PMID-18835936_T26",
"type": "Cell",
"text": [
"endothelial cells"
],
"offsets": [
[
1180,
1197
]
],
"normalized": []
},
{
"id": "PMID-18835936_T28",
"type": "Tissue",
"text": [
"adipose tissue"
],
"offsets": [
[
1225,
1239
]
],
"normalized": []
},
{
"id": "PMID-18835936_T30",
"type": "Tissue",
"text": [
"SAT samples"
],
"offsets": [
[
1318,
1329
]
],
"normalized": []
},
{
"id": "PMID-18835936_T31",
"type": "Tissue",
"text": [
"VAT samples"
],
"offsets": [
[
1341,
1352
]
],
"normalized": []
},
{
"id": "PMID-18835936_T32",
"type": "Cell",
"text": [
"adipocyte"
],
"offsets": [
[
1360,
1369
]
],
"normalized": []
},
{
"id": "PMID-18835936_T33",
"type": "Multi-tissue_structure",
"text": [
"CAM"
],
"offsets": [
[
1450,
1453
]
],
"normalized": []
},
{
"id": "PMID-18835936_T35",
"type": "Tissue",
"text": [
"adipose tissue"
],
"offsets": [
[
1486,
1500
]
],
"normalized": []
},
{
"id": "PMID-18835936_T37",
"type": "Drug_or_compound",
"text": [
"bevacizumab"
],
"offsets": [
[
1525,
1536
]
],
"normalized": []
},
{
"id": "PMID-18835936_T38",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1571,
1575
]
],
"normalized": []
},
{
"id": "PMID-18835936_T40",
"type": "Tissue",
"text": [
"adipose tissue"
],
"offsets": [
[
1667,
1681
]
],
"normalized": []
},
{
"id": "PMID-18835936_T42",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1718,
1722
]
],
"normalized": []
},
{
"id": "PMID-18835936_T44",
"type": "Tissue",
"text": [
"SAT"
],
"offsets": [
[
1747,
1750
]
],
"normalized": []
},
{
"id": "PMID-18835936_T45",
"type": "Tissue",
"text": [
"VAT"
],
"offsets": [
[
1755,
1758
]
],
"normalized": []
},
{
"id": "PMID-18835936_T41",
"type": "Tissue",
"text": [
"SAT"
],
"offsets": [
[
713,
716
]
],
"normalized": []
},
{
"id": "PMID-18835936_T46",
"type": "Tissue",
"text": [
"VAT"
],
"offsets": [
[
721,
724
]
],
"normalized": []
},
{
"id": "PMID-18835936_T47",
"type": "Tissue",
"text": [
"Adipose tissue"
],
"offsets": [
[
843,
857
]
],
"normalized": []
},
{
"id": "PMID-18835936_T48",
"type": "Tissue",
"text": [
"graft"
],
"offsets": [
[
1441,
1446
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1000",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
80,
85
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1001",
"type": "Organism",
"text": [
"humans"
],
"offsets": [
[
246,
252
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1002",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
431,
439
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1003",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
586,
594
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1004",
"type": "Organism",
"text": [
"chick"
],
"offsets": [
[
661,
666
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1005",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
1174,
1179
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1006",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
1565,
1570
]
],
"normalized": []
},
{
"id": "PMID-18835936_T1007",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
1661,
1666
]
],
"normalized": []
},
{
"id": "PMID-18835936_T59",
"type": "Organism",
"text": [
"avian"
],
"offsets": [
[
1164,
1169
]
],
"normalized": []
},
{
"id": "PMID-18835936_T62",
"type": "Tissue",
"text": [
"adipose samples"
],
"offsets": [
[
1414,
1429
]
],
"normalized": []
}
] | [
{
"id": "PMID-18835936_E1",
"type": "Development",
"trigger": {
"text": [
"expansion"
],
"offsets": [
[
111,
120
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T4"
}
]
},
{
"id": "PMID-18835936_E2",
"type": "Development",
"trigger": {
"text": [
"development"
],
"offsets": [
[
156,
167
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T5"
}
]
},
{
"id": "PMID-18835936_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
201,
211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_E23"
}
]
},
{
"id": "PMID-18835936_E4",
"type": "Planned_process",
"trigger": {
"text": [
"obtained"
],
"offsets": [
[
563,
571
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T15"
}
]
},
{
"id": "PMID-18835936_E5",
"type": "Planned_process",
"trigger": {
"text": [
"obtained"
],
"offsets": [
[
563,
571
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T14"
}
]
},
{
"id": "PMID-18835936_E6",
"type": "Planned_process",
"trigger": {
"text": [
"layered"
],
"offsets": [
[
650,
657
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T15"
}
]
},
{
"id": "PMID-18835936_E7",
"type": "Planned_process",
"trigger": {
"text": [
"layered"
],
"offsets": [
[
650,
657
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T14"
}
]
},
{
"id": "PMID-18835936_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
831,
841
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T19"
}
]
},
{
"id": "PMID-18835936_E9",
"type": "Planned_process",
"trigger": {
"text": [
"layered"
],
"offsets": [
[
858,
865
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T47"
}
]
},
{
"id": "PMID-18835936_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
"offsets": [
[
873,
883
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T47"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_E26"
}
]
},
{
"id": "PMID-18835936_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
909,
920
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_E27"
}
]
},
{
"id": "PMID-18835936_E12",
"type": "Binding",
"trigger": {
"text": [
"connection"
],
"offsets": [
[
1050,
1060
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T24"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_T25"
}
]
},
{
"id": "PMID-18835936_E13",
"type": "Localization",
"trigger": {
"text": [
"recruitment"
],
"offsets": [
[
1144,
1155
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T26"
}
]
},
{
"id": "PMID-18835936_E14",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
1263,
1275
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_T28"
}
]
},
{
"id": "PMID-18835936_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulation"
],
"offsets": [
[
1296,
1307
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_E29"
}
]
},
{
"id": "PMID-18835936_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"Stimulation"
],
"offsets": [
[
1455,
1466
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_E30"
},
{
"role": "Cause",
"ref_id": "PMID-18835936_T35"
}
]
},
{
"id": "PMID-18835936_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"abolished"
],
"offsets": [
[
1512,
1521
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T37"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_E16"
}
]
},
{
"id": "PMID-18835936_E18",
"type": "Regulation",
"trigger": {
"text": [
"targets"
],
"offsets": [
[
1557,
1564
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T37"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_T38"
}
]
},
{
"id": "PMID-18835936_E19",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1631,
1641
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T40"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_E31"
}
]
},
{
"id": "PMID-18835936_E20",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
1710,
1714
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T42"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_E32"
}
]
},
{
"id": "PMID-18835936_E22",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
0,
12
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T2"
}
]
},
{
"id": "PMID-18835936_E23",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
230,
242
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T6"
}
]
},
{
"id": "PMID-18835936_E24",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
314,
326
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T9"
}
]
},
{
"id": "PMID-18835936_E25",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
735,
745
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E26",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
884,
896
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E27",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenic"
],
"offsets": [
[
898,
908
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E28",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1203,
1213
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T28"
}
]
},
{
"id": "PMID-18835936_E29",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
1285,
1295
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E30",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1470,
1482
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E31",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1645,
1657
]
]
},
"arguments": []
},
{
"id": "PMID-18835936_E32",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1726,
1738
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T44"
}
]
},
{
"id": "PMID-18835936_E33",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
0,
12
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T3"
}
]
},
{
"id": "PMID-18835936_E34",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
314,
326
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T11"
}
]
},
{
"id": "PMID-18835936_E35",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1726,
1738
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-18835936_T45"
}
]
},
{
"id": "PMID-18835936_E36",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
1710,
1714
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-18835936_T42"
},
{
"role": "Theme",
"ref_id": "PMID-18835936_E35"
}
]
},
{
"id": "PMID-18835936_E21",
"type": "Regulation",
"trigger": {
"text": [
"linked"
],
"offsets": [
[
142,
148
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-18835936_E1"
},
{
"role": "Cause",
"ref_id": "PMID-18835936_E2"
}
]
}
] | [
{
"id": "PMID-18835936_1",
"entity_ids": [
"PMID-18835936_T19",
"PMID-18835936_T20"
]
},
{
"id": "PMID-18835936_2",
"entity_ids": [
"PMID-18835936_T9",
"PMID-18835936_T10"
]
},
{
"id": "PMID-18835936_3",
"entity_ids": [
"PMID-18835936_T11",
"PMID-18835936_T12"
]
},
{
"id": "PMID-18835936_4",
"entity_ids": [
"PMID-18835936_T16",
"PMID-18835936_T17"
]
}
] | [
{
"id": "PMID-18835936_R1",
"type": "frag",
"arg1_id": "PMID-18835936_T2",
"arg2_id": "PMID-18835936_T3",
"normalized": []
}
] |
13 | PMID-12823209 | [
{
"id": "PMID-12823209__text",
"type": "abstract",
"text": [
"Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of the esophagus.\n\nThe most common genetic alterations found in a wide variety of cancers are p53 tumor suppressor gene mutations. p53 appears to be a nuclear transcription factor that plays a role in the control of cell proliferation, apoptosis, and the maintenance of genetic stability. Angiogenesis is a critical process in solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator. Few studies have investigated the association between p53 and VEGF expressions and prognosis in esophageal carcinoma. Forty-seven specimens resected from patients with stage II and III squamous cell carcinoma (SCC) of the esophagus were studied using immunohistochemical staining. VEGF and p53 expressions were observed in 40% and 53% of the tumors, respectively. The p53 and VEGF staining statuses were coincident in only 21% of the tumors, and no significant correlation was found between p53 and VEGF statuses. No clinicopathologic factors were significantly correlated with p53 or VEGF expression. No significant association between p53 and VEGF expressions and poor prognosis was found. In conclusion, p53 and VEGF were not correlated with prognosis in patients with stage II and III SCC of the esophagus.\n"
],
"offsets": [
[
0,
1466
]
]
}
] | [
{
"id": "PMID-12823209_T2",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
20,
23
]
],
"normalized": []
},
{
"id": "PMID-12823209_T4",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
47,
81
]
],
"normalized": []
},
{
"id": "PMID-12823209_T5",
"type": "Pathological_formation",
"text": [
"squamous cell carcinoma"
],
"offsets": [
[
105,
128
]
],
"normalized": []
},
{
"id": "PMID-12823209_T6",
"type": "Organ",
"text": [
"esophagus"
],
"offsets": [
[
136,
145
]
],
"normalized": []
},
{
"id": "PMID-12823209_T8",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
223,
226
]
],
"normalized": []
},
{
"id": "PMID-12823209_T9",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
260,
263
]
],
"normalized": []
},
{
"id": "PMID-12823209_T15",
"type": "Pathological_formation",
"text": [
"solid tumor"
],
"offsets": [
[
456,
467
]
],
"normalized": []
},
{
"id": "PMID-12823209_T16",
"type": "Gene_or_gene_product",
"text": [
"Vascular endothelial growth factor"
],
"offsets": [
[
491,
525
]
],
"normalized": []
},
{
"id": "PMID-12823209_T17",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
527,
531
]
],
"normalized": []
},
{
"id": "PMID-12823209_T19",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
625,
630
]
],
"normalized": []
},
{
"id": "PMID-12823209_T23",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
709,
712
]
],
"normalized": []
},
{
"id": "PMID-12823209_T25",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
717,
721
]
],
"normalized": []
},
{
"id": "PMID-12823209_T26",
"type": "Pathological_formation",
"text": [
"esophageal carcinoma"
],
"offsets": [
[
751,
771
]
],
"normalized": []
},
{
"id": "PMID-12823209_T27",
"type": "Pathological_formation",
"text": [
"squamous cell carcinoma"
],
"offsets": [
[
840,
863
]
],
"normalized": []
},
{
"id": "PMID-12823209_T28",
"type": "Organ",
"text": [
"esophagus"
],
"offsets": [
[
877,
886
]
],
"normalized": []
},
{
"id": "PMID-12823209_T30",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
936,
940
]
],
"normalized": []
},
{
"id": "PMID-12823209_T32",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
945,
948
]
],
"normalized": []
},
{
"id": "PMID-12823209_T33",
"type": "Pathological_formation",
"text": [
"tumors"
],
"offsets": [
[
997,
1003
]
],
"normalized": []
},
{
"id": "PMID-12823209_T34",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
1023,
1026
]
],
"normalized": []
},
{
"id": "PMID-12823209_T35",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1031,
1035
]
],
"normalized": []
},
{
"id": "PMID-12823209_T36",
"type": "Pathological_formation",
"text": [
"tumors"
],
"offsets": [
[
1089,
1095
]
],
"normalized": []
},
{
"id": "PMID-12823209_T37",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
1146,
1149
]
],
"normalized": []
},
{
"id": "PMID-12823209_T38",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1154,
1158
]
],
"normalized": []
},
{
"id": "PMID-12823209_T40",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
1233,
1236
]
],
"normalized": []
},
{
"id": "PMID-12823209_T42",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1240,
1244
]
],
"normalized": []
},
{
"id": "PMID-12823209_T44",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
1292,
1295
]
],
"normalized": []
},
{
"id": "PMID-12823209_T46",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1300,
1304
]
],
"normalized": []
},
{
"id": "PMID-12823209_T47",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
1362,
1365
]
],
"normalized": []
},
{
"id": "PMID-12823209_T48",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1370,
1374
]
],
"normalized": []
},
{
"id": "PMID-12823209_T49",
"type": "Organ",
"text": [
"esophagus"
],
"offsets": [
[
1455,
1464
]
],
"normalized": []
},
{
"id": "PMID-12823209_T12",
"type": "Pathological_formation",
"text": [
"SCC"
],
"offsets": [
[
865,
868
]
],
"normalized": []
},
{
"id": "PMID-12823209_T21",
"type": "Pathological_formation",
"text": [
"SCC"
],
"offsets": [
[
1444,
1447
]
],
"normalized": []
},
{
"id": "PMID-12823209_T50",
"type": "Pathological_formation",
"text": [
"cancers"
],
"offsets": [
[
211,
218
]
],
"normalized": []
},
{
"id": "PMID-12823209_T1000",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
809,
817
]
],
"normalized": []
},
{
"id": "PMID-12823209_T1001",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1413,
1421
]
],
"normalized": []
},
{
"id": "PMID-12823209_T41",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
345,
349
]
],
"normalized": []
}
] | [
{
"id": "PMID-12823209_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
32,
42
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T2"
}
]
},
{
"id": "PMID-12823209_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
82,
92
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T4"
}
]
},
{
"id": "PMID-12823209_E13",
"type": "Localization",
"trigger": {
"text": [
"metastasis"
],
"offsets": [
[
479,
489
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T15"
}
]
},
{
"id": "PMID-12823209_E14",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
468,
474
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T15"
}
]
},
{
"id": "PMID-12823209_E22",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
722,
733
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T25"
}
]
},
{
"id": "PMID-12823209_E29",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
949,
960
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T32"
}
]
},
{
"id": "PMID-12823209_E39",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1245,
1255
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T42"
}
]
},
{
"id": "PMID-12823209_E43",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
1305,
1316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T46"
}
]
},
{
"id": "PMID-12823209_E2",
"type": "Planned_process",
"trigger": {
"text": [
"resected"
],
"offsets": [
[
96,
104
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T5"
}
]
},
{
"id": "PMID-12823209_E5",
"type": "Regulation",
"trigger": {
"text": [
"critical"
],
"offsets": [
[
436,
444
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12823209_E19"
},
{
"role": "Theme",
"ref_id": "PMID-12823209_E14"
}
]
},
{
"id": "PMID-12823209_E6",
"type": "Regulation",
"trigger": {
"text": [
"critical"
],
"offsets": [
[
436,
444
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12823209_E19"
},
{
"role": "Theme",
"ref_id": "PMID-12823209_E13"
}
]
},
{
"id": "PMID-12823209_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
722,
733
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T23"
}
]
},
{
"id": "PMID-12823209_E8",
"type": "Planned_process",
"trigger": {
"text": [
"resected"
],
"offsets": [
[
795,
803
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T27"
}
]
},
{
"id": "PMID-12823209_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
949,
960
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T30"
}
]
},
{
"id": "PMID-12823209_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1245,
1255
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T40"
}
]
},
{
"id": "PMID-12823209_E11",
"type": "Regulation",
"trigger": {
"text": [
"regulator"
],
"offsets": [
[
644,
653
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12823209_T16"
},
{
"role": "Theme",
"ref_id": "PMID-12823209_E21"
}
]
},
{
"id": "PMID-12823209_E15",
"type": "Death",
"trigger": {
"text": [
"apoptosis"
],
"offsets": [
[
365,
374
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T41"
}
]
},
{
"id": "PMID-12823209_E16",
"type": "Cell_proliferation",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
350,
363
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T41"
}
]
},
{
"id": "PMID-12823209_E17",
"type": "Regulation",
"trigger": {
"text": [
"control"
],
"offsets": [
[
334,
341
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12823209_T9"
},
{
"role": "Theme",
"ref_id": "PMID-12823209_E16"
}
]
},
{
"id": "PMID-12823209_E12",
"type": "Regulation",
"trigger": {
"text": [
"control"
],
"offsets": [
[
334,
341
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-12823209_T9"
},
{
"role": "Theme",
"ref_id": "PMID-12823209_E15"
}
]
},
{
"id": "PMID-12823209_E18",
"type": "Gene_expression",
"trigger": {
"text": [
"expressions"
],
"offsets": [
[
1305,
1316
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-12823209_T44"
}
]
},
{
"id": "PMID-12823209_E19",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"Angiogenesis"
],
"offsets": [
[
418,
430
]
]
},
"arguments": []
},
{
"id": "PMID-12823209_E20",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
587,
597
]
]
},
"arguments": []
},
{
"id": "PMID-12823209_E21",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
631,
643
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-12823209_T19"
}
]
}
] | [
{
"id": "PMID-12823209_1",
"entity_ids": [
"PMID-12823209_T16",
"PMID-12823209_T17"
]
},
{
"id": "PMID-12823209_2",
"entity_ids": [
"PMID-12823209_T27",
"PMID-12823209_T12"
]
}
] | [] |
14 | PMID-10487573 | [
{
"id": "PMID-10487573__text",
"type": "abstract",
"text": [
"External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient?\n\nPURPOSE: Control of the natural course of subretinal neovascularization (SRNV) in age-related macular degeneration (AMD) is difficult. Only a subset of patients is suitable for laser coagulation. This prospective study aimed to determine the efficacy and individual benefit of external beam radiotherapy (EBRT). METHODS AND MATERIALS: The prospective trial included 287 patients with subfoveal neovascularization due to AMD which was verified by fluorescein angiography. Patients have been treated between January 1996 and October 1997. All patients received a total dose of 16 Gy in 2-Gy daily fractions with 5-6 MeV photons based on computerized treatment planning in individual head mask fixation. This first analysis is based on 73 patients (50 women, 23 men, median age 74.3 years), with a median follow-up of 13.3 months and a minimum follow-up of 11 months. RESULTS: All patients completed therapy and tolerability was good. First clinical control with second angiography was performed 6 weeks after irradiation, then in 3-month intervals. Eighteen patients with SRNV refusing radiotherapy served as a control group and were matched with 18 irradiated patients. After 7 months median visual acuity (VA) was 20/160 for the irradiated and 20/400 for the untreated patients. One year after radiotherapy final median VA was 20/400 in both groups. CONCLUSION: These results suggest that 16 Gy of conventionally fractionated external beam irradiation slows down the visual loss in exudative AMD for only a few months. Patients' reading vision could not be saved for a long-term run.\n"
],
"offsets": [
[
0,
1712
]
]
}
] | [
{
"id": "PMID-10487573_T4",
"type": "Tissue",
"text": [
"macular"
],
"offsets": [
[
76,
83
]
],
"normalized": []
},
{
"id": "PMID-10487573_T8",
"type": "Tissue",
"text": [
"macular"
],
"offsets": [
[
222,
229
]
],
"normalized": []
},
{
"id": "PMID-10487573_T10",
"type": "Drug_or_compound",
"text": [
"fluorescein"
],
"offsets": [
[
574,
585
]
],
"normalized": []
},
{
"id": "PMID-10487573_T11",
"type": "Organism_subdivision",
"text": [
"head"
],
"offsets": [
[
809,
813
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1000",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
280,
288
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1001",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
498,
506
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1002",
"type": "Organism",
"text": [
"Patients"
],
"offsets": [
[
599,
607
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1003",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
669,
677
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1004",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
864,
872
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1005",
"type": "Organism",
"text": [
"women"
],
"offsets": [
[
877,
882
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1006",
"type": "Organism",
"text": [
"men"
],
"offsets": [
[
887,
890
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1007",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1006,
1014
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1008",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1184,
1192
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1009",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1287,
1295
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1010",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1397,
1405
]
],
"normalized": []
},
{
"id": "PMID-10487573_T1011",
"type": "Organism",
"text": [
"Patients"
],
"offsets": [
[
1647,
1655
]
],
"normalized": []
}
] | [
{
"id": "PMID-10487573_E3",
"type": "Breakdown",
"trigger": {
"text": [
"degeneration"
],
"offsets": [
[
84,
96
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T4"
}
]
},
{
"id": "PMID-10487573_E7",
"type": "Breakdown",
"trigger": {
"text": [
"degeneration"
],
"offsets": [
[
230,
242
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T8"
}
]
},
{
"id": "PMID-10487573_E1",
"type": "Regulation",
"trigger": {
"text": [
"Control"
],
"offsets": [
[
137,
144
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_E13"
}
]
},
{
"id": "PMID-10487573_E2",
"type": "Planned_process",
"trigger": {
"text": [
"treated"
],
"offsets": [
[
618,
625
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1002"
}
]
},
{
"id": "PMID-10487573_E4",
"type": "Planned_process",
"trigger": {
"text": [
"received"
],
"offsets": [
[
678,
686
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1003"
}
]
},
{
"id": "PMID-10487573_E5",
"type": "Planned_process",
"trigger": {
"text": [
"therapy"
],
"offsets": [
[
1025,
1032
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1007"
}
]
},
{
"id": "PMID-10487573_E6",
"type": "Planned_process",
"trigger": {
"text": [
"irradiated"
],
"offsets": [
[
1357,
1367
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1010"
}
]
},
{
"id": "PMID-10487573_E8",
"type": "Planned_process",
"trigger": {
"text": [
"untreated"
],
"offsets": [
[
1387,
1396
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1010"
}
]
},
{
"id": "PMID-10487573_E9",
"type": "Planned_process",
"trigger": {
"text": [
"irradiated"
],
"offsets": [
[
1276,
1286
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1009"
}
]
},
{
"id": "PMID-10487573_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"refusing"
],
"offsets": [
[
1203,
1211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_E11"
}
]
},
{
"id": "PMID-10487573_E11",
"type": "Planned_process",
"trigger": {
"text": [
"radiotherapy"
],
"offsets": [
[
1212,
1224
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10487573_T1008"
}
]
},
{
"id": "PMID-10487573_E12",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"neovascularization"
],
"offsets": [
[
42,
60
]
]
},
"arguments": []
},
{
"id": "PMID-10487573_E13",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"neovascularization"
],
"offsets": [
[
181,
199
]
]
},
"arguments": []
},
{
"id": "PMID-10487573_E14",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"neovascularization"
],
"offsets": [
[
522,
540
]
]
},
"arguments": []
}
] | [] | [] |
15 | PMID-10978899 | [
{
"id": "PMID-10978899__text",
"type": "abstract",
"text": [
"Urokinase receptor: a molecular organizer in cellular communication.\n\nIn a variety of cell types, the glycolipid-anchored urokinase receptor (uPAR) is colocalized pericellularly with components of the plasminogen activation system and endocytosis receptors. uPAR is also coexpressed with caveolin and members of the integrin adhesion receptor superfamily. The formation of functional units with these various proteins allows the uPAR to mediate the focused proteolysis required for cell migration and invasion and to contribute both directly and indirectly to cell adhesive processes in a non-proteolytic fashion. This dual activity, together with the initiation of signal transduction pathways by uPAR, is believed to influence cellular behaviour in angiogenesis, inflammation, wound repair and tumor progression/metastasis and open up the way for uPAR-based therapeutic approaches.\n"
],
"offsets": [
[
0,
884
]
]
}
] | [
{
"id": "PMID-10978899_T1",
"type": "Gene_or_gene_product",
"text": [
"Urokinase receptor"
],
"offsets": [
[
0,
18
]
],
"normalized": []
},
{
"id": "PMID-10978899_T2",
"type": "Gene_or_gene_product",
"text": [
"glycolipid-anchored urokinase receptor"
],
"offsets": [
[
102,
140
]
],
"normalized": []
},
{
"id": "PMID-10978899_T3",
"type": "Gene_or_gene_product",
"text": [
"uPAR"
],
"offsets": [
[
142,
146
]
],
"normalized": []
},
{
"id": "PMID-10978899_T4",
"type": "Gene_or_gene_product",
"text": [
"plasminogen"
],
"offsets": [
[
201,
212
]
],
"normalized": []
},
{
"id": "PMID-10978899_T7",
"type": "Gene_or_gene_product",
"text": [
"uPAR"
],
"offsets": [
[
258,
262
]
],
"normalized": []
},
{
"id": "PMID-10978899_T8",
"type": "Gene_or_gene_product",
"text": [
"caveolin"
],
"offsets": [
[
288,
296
]
],
"normalized": []
},
{
"id": "PMID-10978899_T10",
"type": "Gene_or_gene_product",
"text": [
"uPAR"
],
"offsets": [
[
429,
433
]
],
"normalized": []
},
{
"id": "PMID-10978899_T12",
"type": "Gene_or_gene_product",
"text": [
"uPAR"
],
"offsets": [
[
698,
702
]
],
"normalized": []
},
{
"id": "PMID-10978899_T15",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
796,
801
]
],
"normalized": []
},
{
"id": "PMID-10978899_T16",
"type": "Gene_or_gene_product",
"text": [
"uPAR"
],
"offsets": [
[
849,
853
]
],
"normalized": []
},
{
"id": "PMID-10978899_T13",
"type": "Gene_or_gene_product",
"text": [
"integrin adhesion receptor"
],
"offsets": [
[
316,
342
]
],
"normalized": []
},
{
"id": "PMID-10978899_T20",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
86,
90
]
],
"normalized": []
},
{
"id": "PMID-10978899_T21",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
482,
486
]
],
"normalized": []
},
{
"id": "PMID-10978899_T25",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
560,
564
]
],
"normalized": []
},
{
"id": "PMID-10978899_T28",
"type": "Pathological_formation",
"text": [
"wound"
],
"offsets": [
[
779,
784
]
],
"normalized": []
}
] | [
{
"id": "PMID-10978899_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpressed"
],
"offsets": [
[
271,
282
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T7"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_T8"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_T13"
}
]
},
{
"id": "PMID-10978899_E1",
"type": "Localization",
"trigger": {
"text": [
"colocalized"
],
"offsets": [
[
151,
162
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T2"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_T4"
},
{
"role": "AtLoc",
"ref_id": "PMID-10978899_T20"
}
]
},
{
"id": "PMID-10978899_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"initiation"
],
"offsets": [
[
652,
662
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_E16"
},
{
"role": "Cause",
"ref_id": "PMID-10978899_T12"
}
]
},
{
"id": "PMID-10978899_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
719,
728
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10978899_E2"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_E15"
}
]
},
{
"id": "PMID-10978899_E4",
"type": "Development",
"trigger": {
"text": [
"progression"
],
"offsets": [
[
802,
813
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T15"
}
]
},
{
"id": "PMID-10978899_E5",
"type": "Localization",
"trigger": {
"text": [
"metastasis"
],
"offsets": [
[
814,
824
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T15"
}
]
},
{
"id": "PMID-10978899_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
719,
728
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10978899_E2"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_E4"
}
]
},
{
"id": "PMID-10978899_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
719,
728
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10978899_E2"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_E5"
}
]
},
{
"id": "PMID-10978899_E9",
"type": "Localization",
"trigger": {
"text": [
"migration"
],
"offsets": [
[
487,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T21"
}
]
},
{
"id": "PMID-10978899_E10",
"type": "Localization",
"trigger": {
"text": [
"invasion"
],
"offsets": [
[
501,
509
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T21"
}
]
},
{
"id": "PMID-10978899_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
469,
477
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_E9"
}
]
},
{
"id": "PMID-10978899_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
469,
477
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_E10"
}
]
},
{
"id": "PMID-10978899_E13",
"type": "Binding",
"trigger": {
"text": [
"adhesive processes"
],
"offsets": [
[
565,
583
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-10978899_T25"
}
]
},
{
"id": "PMID-10978899_E14",
"type": "Regulation",
"trigger": {
"text": [
"contribute"
],
"offsets": [
[
517,
527
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-10978899_T10"
},
{
"role": "Theme",
"ref_id": "PMID-10978899_E13"
}
]
},
{
"id": "PMID-10978899_E15",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
751,
763
]
]
},
"arguments": []
},
{
"id": "PMID-10978899_E16",
"type": "Pathway",
"trigger": {
"text": [
"signal transduction pathways"
],
"offsets": [
[
666,
694
]
]
},
"arguments": []
}
] | [
{
"id": "PMID-10978899_1",
"entity_ids": [
"PMID-10978899_T2",
"PMID-10978899_T3"
]
}
] | [] |
16 | PMID-16398404 | [
{
"id": "PMID-16398404__text",
"type": "abstract",
"text": [
"The differential regulation of human telomerase reverse transcriptase and vascular endothelial growth factor may contribute to the clinically more aggressive behavior of p63-positive breast carcinomas.\n\np63, a p53 homologue, is a myoepithelial cell marker in the normal mammary gland but p63-positive neoplastic cells may be found in up to 11% of invasive breast carcinomas. This study aims to verify the relationship between p63 expression and several clinicopathological features and tumor markers of clinical significance in breast pathology including key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. p63-positive cells were found in 16% of carcinomas. p63-positive carcinomas were poorly differentiated, hormone receptor-negative neoplasms with a high proliferation rate. p63 also correlated with advanced pathological stage, tumor size, and the expression of human telomerase reverse transcriptase (hTERT), tissue inhibitor of matrix metalloproteinase 1 (TIMP1) and vascular endothelial growth factor (VEGF). The expression of TIMP1 suggests that the anti-proteolytic stimuli may be preponderant in p63-positive carcinomas. hTERT activity is associated with nodal metastases and cellular proliferation. VEGF regulates angiogenesis, which is also a fundamental event in the process of tumor growth and metastatic dissemination. Thus, the differential regulation of hTERT and VEGF in p63-positive breast carcinomas may contribute to the clinically more aggressive behavior of these neoplasms.\n"
],
"offsets": [
[
0,
1702
]
]
}
] | [
{
"id": "PMID-16398404_T3",
"type": "Gene_or_gene_product",
"text": [
"telomerase reverse transcriptase"
],
"offsets": [
[
37,
69
]
],
"normalized": []
},
{
"id": "PMID-16398404_T4",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
74,
108
]
],
"normalized": []
},
{
"id": "PMID-16398404_T5",
"type": "Pathological_formation",
"text": [
"p63-positive breast carcinomas"
],
"offsets": [
[
170,
200
]
],
"normalized": []
},
{
"id": "PMID-16398404_T6",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
170,
173
]
],
"normalized": []
},
{
"id": "PMID-16398404_T8",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
203,
206
]
],
"normalized": []
},
{
"id": "PMID-16398404_T10",
"type": "Gene_or_gene_product",
"text": [
"p53"
],
"offsets": [
[
210,
213
]
],
"normalized": []
},
{
"id": "PMID-16398404_T11",
"type": "Cell",
"text": [
"myoepithelial cell"
],
"offsets": [
[
230,
248
]
],
"normalized": []
},
{
"id": "PMID-16398404_T12",
"type": "Organ",
"text": [
"mammary gland"
],
"offsets": [
[
270,
283
]
],
"normalized": []
},
{
"id": "PMID-16398404_T13",
"type": "Cell",
"text": [
"p63-positive neoplastic cells"
],
"offsets": [
[
288,
317
]
],
"normalized": []
},
{
"id": "PMID-16398404_T14",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
288,
291
]
],
"normalized": []
},
{
"id": "PMID-16398404_T15",
"type": "Pathological_formation",
"text": [
"invasive breast carcinomas"
],
"offsets": [
[
347,
373
]
],
"normalized": []
},
{
"id": "PMID-16398404_T18",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
426,
429
]
],
"normalized": []
},
{
"id": "PMID-16398404_T19",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
486,
491
]
],
"normalized": []
},
{
"id": "PMID-16398404_T20",
"type": "Organism_subdivision",
"text": [
"breast"
],
"offsets": [
[
528,
534
]
],
"normalized": []
},
{
"id": "PMID-16398404_T21",
"type": "Pathological_formation",
"text": [
"invasive ductal carcinomas"
],
"offsets": [
[
782,
808
]
],
"normalized": []
},
{
"id": "PMID-16398404_T22",
"type": "Cell",
"text": [
"p63-positive cells"
],
"offsets": [
[
810,
828
]
],
"normalized": []
},
{
"id": "PMID-16398404_T23",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
810,
813
]
],
"normalized": []
},
{
"id": "PMID-16398404_T24",
"type": "Pathological_formation",
"text": [
"carcinomas"
],
"offsets": [
[
850,
860
]
],
"normalized": []
},
{
"id": "PMID-16398404_T25",
"type": "Cell",
"text": [
"p63-positive carcinomas"
],
"offsets": [
[
862,
885
]
],
"normalized": []
},
{
"id": "PMID-16398404_T26",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
862,
865
]
],
"normalized": []
},
{
"id": "PMID-16398404_T27",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
982,
985
]
],
"normalized": []
},
{
"id": "PMID-16398404_T28",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1036,
1041
]
],
"normalized": []
},
{
"id": "PMID-16398404_T32",
"type": "Gene_or_gene_product",
"text": [
"telomerase reverse transcriptase"
],
"offsets": [
[
1076,
1108
]
],
"normalized": []
},
{
"id": "PMID-16398404_T33",
"type": "Gene_or_gene_product",
"text": [
"hTERT"
],
"offsets": [
[
1110,
1115
]
],
"normalized": []
},
{
"id": "PMID-16398404_T34",
"type": "Gene_or_gene_product",
"text": [
"tissue inhibitor of matrix metalloproteinase 1"
],
"offsets": [
[
1118,
1164
]
],
"normalized": []
},
{
"id": "PMID-16398404_T35",
"type": "Gene_or_gene_product",
"text": [
"TIMP1"
],
"offsets": [
[
1166,
1171
]
],
"normalized": []
},
{
"id": "PMID-16398404_T36",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factor"
],
"offsets": [
[
1177,
1211
]
],
"normalized": []
},
{
"id": "PMID-16398404_T37",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1213,
1217
]
],
"normalized": []
},
{
"id": "PMID-16398404_T39",
"type": "Gene_or_gene_product",
"text": [
"TIMP1"
],
"offsets": [
[
1238,
1243
]
],
"normalized": []
},
{
"id": "PMID-16398404_T40",
"type": "Pathological_formation",
"text": [
"p63-positive carcinomas"
],
"offsets": [
[
1310,
1333
]
],
"normalized": []
},
{
"id": "PMID-16398404_T41",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
1310,
1313
]
],
"normalized": []
},
{
"id": "PMID-16398404_T42",
"type": "Gene_or_gene_product",
"text": [
"hTERT"
],
"offsets": [
[
1335,
1340
]
],
"normalized": []
},
{
"id": "PMID-16398404_T44",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1414,
1418
]
],
"normalized": []
},
{
"id": "PMID-16398404_T48",
"type": "Pathological_formation",
"text": [
"tumor"
],
"offsets": [
[
1495,
1500
]
],
"normalized": []
},
{
"id": "PMID-16398404_T50",
"type": "Gene_or_gene_product",
"text": [
"hTERT"
],
"offsets": [
[
1575,
1580
]
],
"normalized": []
},
{
"id": "PMID-16398404_T51",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
1585,
1589
]
],
"normalized": []
},
{
"id": "PMID-16398404_T52",
"type": "Pathological_formation",
"text": [
"p63-positive breast carcinomas"
],
"offsets": [
[
1593,
1623
]
],
"normalized": []
},
{
"id": "PMID-16398404_T53",
"type": "Gene_or_gene_product",
"text": [
"p63"
],
"offsets": [
[
1593,
1596
]
],
"normalized": []
},
{
"id": "PMID-16398404_T54",
"type": "Pathological_formation",
"text": [
"neoplasms"
],
"offsets": [
[
1691,
1700
]
],
"normalized": []
},
{
"id": "PMID-16398404_T9",
"type": "Gene_or_gene_product",
"text": [
"metalloproteinases"
],
"offsets": [
[
628,
646
]
],
"normalized": []
},
{
"id": "PMID-16398404_T43",
"type": "Pathological_formation",
"text": [
"neoplasms"
],
"offsets": [
[
940,
949
]
],
"normalized": []
},
{
"id": "PMID-16398404_T1000",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
31,
36
]
],
"normalized": []
},
{
"id": "PMID-16398404_T1001",
"type": "Organism",
"text": [
"human"
],
"offsets": [
[
1070,
1075
]
],
"normalized": []
},
{
"id": "PMID-16398404_T45",
"type": "Cell",
"text": [
"cell"
],
"offsets": [
[
577,
581
]
],
"normalized": []
}
] | [
{
"id": "PMID-16398404_E2",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
17,
27
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T3"
}
]
},
{
"id": "PMID-16398404_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
430,
440
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T18"
}
]
},
{
"id": "PMID-16398404_E31",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1056,
1066
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T32"
}
]
},
{
"id": "PMID-16398404_E38",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1224,
1234
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T39"
}
]
},
{
"id": "PMID-16398404_E47",
"type": "Growth",
"trigger": {
"text": [
"growth"
],
"offsets": [
[
1501,
1507
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T48"
}
]
},
{
"id": "PMID-16398404_E49",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1561,
1571
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T52"
},
{
"role": "Cause",
"ref_id": "PMID-16398404_T50"
}
]
},
{
"id": "PMID-16398404_E1",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
17,
27
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T4"
}
]
},
{
"id": "PMID-16398404_E3",
"type": "Localization",
"trigger": {
"text": [
"found"
],
"offsets": [
[
834,
839
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T22"
},
{
"role": "AtLoc",
"ref_id": "PMID-16398404_T24"
}
]
},
{
"id": "PMID-16398404_E4",
"type": "Development",
"trigger": {
"text": [
"differentiated"
],
"offsets": [
[
898,
912
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T25"
}
]
},
{
"id": "PMID-16398404_E5",
"type": "Growth",
"trigger": {
"text": [
"proliferation"
],
"offsets": [
[
962,
975
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T43"
}
]
},
{
"id": "PMID-16398404_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1056,
1066
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T34"
}
]
},
{
"id": "PMID-16398404_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1056,
1066
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T36"
}
]
},
{
"id": "PMID-16398404_E8",
"type": "Regulation",
"trigger": {
"text": [
"regulates"
],
"offsets": [
[
1419,
1428
]
]
},
"arguments": [
{
"role": "Cause",
"ref_id": "PMID-16398404_T44"
},
{
"role": "Theme",
"ref_id": "PMID-16398404_E11"
}
]
},
{
"id": "PMID-16398404_E9",
"type": "Localization",
"trigger": {
"text": [
"metastatic dissemination"
],
"offsets": [
[
1512,
1536
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T48"
}
]
},
{
"id": "PMID-16398404_E10",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1561,
1571
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-16398404_T52"
},
{
"role": "Cause",
"ref_id": "PMID-16398404_T51"
}
]
},
{
"id": "PMID-16398404_E11",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
1429,
1441
]
]
},
"arguments": []
}
] | [
{
"id": "PMID-16398404_1",
"entity_ids": [
"PMID-16398404_T33",
"PMID-16398404_T32"
]
},
{
"id": "PMID-16398404_2",
"entity_ids": [
"PMID-16398404_T34",
"PMID-16398404_T35"
]
},
{
"id": "PMID-16398404_3",
"entity_ids": [
"PMID-16398404_T36",
"PMID-16398404_T37"
]
}
] | [] |
17 | PMID-19236257 | [
{
"id": "PMID-19236257__text",
"type": "abstract",
"text": [
"Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors.\n\nBACKGROUND: Aberrant angiogenesis is a landmark feature in cancer, which is important for proliferation, growth and metastasis, and is mediated by various pro-angiogenic factors. The VEGF pathway is one of the most important and best-studied angiogenic pathways. Inhibition of this pathway may provide clinical benefits to cancer patients. OBJECTIVES: Strategies to inhibit the VEGF pathway, including antibodies to VEGF, antibodies to the extracellular domain of VEGFR-1 or VEGFR-2, decoy receptors for VEGF and tyrosine kinase inhibitors of VEGFRs, are summarized. METHODS: This review outlines and compares the latest development of these strategies, with emphasis on aflibercept, a novel decoy fusion protein of domain 2 of VEGFR-1 and domain 3 of VEGFR-2 with the Fc fragment of IgG1. RESULTS: Aflibercept was shown to have early clinical activity. Multiple studies are ongoing to determine the clinical benefits of aflibercept in cancer patients.\n"
],
"offsets": [
[
0,
1076
]
]
}
] | [
{
"id": "PMID-19236257_T1",
"type": "Drug_or_compound",
"text": [
"Aflibercept"
],
"offsets": [
[
0,
11
]
],
"normalized": []
},
{
"id": "PMID-19236257_T2",
"type": "Drug_or_compound",
"text": [
"AVE0005"
],
"offsets": [
[
13,
20
]
],
"normalized": []
},
{
"id": "PMID-19236257_T4",
"type": "Pathological_formation",
"text": [
"tumour"
],
"offsets": [
[
62,
68
]
],
"normalized": []
},
{
"id": "PMID-19236257_T6",
"type": "Gene_or_gene_product",
"text": [
"vascular endothelial growth factors"
],
"offsets": [
[
85,
120
]
],
"normalized": []
},
{
"id": "PMID-19236257_T10",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
306,
310
]
],
"normalized": []
},
{
"id": "PMID-19236257_T16",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
501,
505
]
],
"normalized": []
},
{
"id": "PMID-19236257_T18",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
539,
543
]
],
"normalized": []
},
{
"id": "PMID-19236257_T21",
"type": "Gene_or_gene_product",
"text": [
"VEGFR-1"
],
"offsets": [
[
587,
594
]
],
"normalized": []
},
{
"id": "PMID-19236257_T22",
"type": "Gene_or_gene_product",
"text": [
"VEGFR-2"
],
"offsets": [
[
598,
605
]
],
"normalized": []
},
{
"id": "PMID-19236257_T24",
"type": "Gene_or_gene_product",
"text": [
"VEGF"
],
"offsets": [
[
627,
631
]
],
"normalized": []
},
{
"id": "PMID-19236257_T25",
"type": "Drug_or_compound",
"text": [
"tyrosine kinase inhibitors"
],
"offsets": [
[
636,
662
]
],
"normalized": []
},
{
"id": "PMID-19236257_T26",
"type": "Gene_or_gene_product",
"text": [
"VEGFRs"
],
"offsets": [
[
666,
672
]
],
"normalized": []
},
{
"id": "PMID-19236257_T27",
"type": "Drug_or_compound",
"text": [
"aflibercept"
],
"offsets": [
[
794,
805
]
],
"normalized": []
},
{
"id": "PMID-19236257_T28",
"type": "Gene_or_gene_product",
"text": [
"VEGFR-1"
],
"offsets": [
[
851,
858
]
],
"normalized": []
},
{
"id": "PMID-19236257_T29",
"type": "Gene_or_gene_product",
"text": [
"VEGFR-2"
],
"offsets": [
[
875,
882
]
],
"normalized": []
},
{
"id": "PMID-19236257_T31",
"type": "Drug_or_compound",
"text": [
"Aflibercept"
],
"offsets": [
[
922,
933
]
],
"normalized": []
},
{
"id": "PMID-19236257_T32",
"type": "Drug_or_compound",
"text": [
"aflibercept"
],
"offsets": [
[
1044,
1055
]
],
"normalized": []
},
{
"id": "PMID-19236257_T3",
"type": "Gene_or_gene_product",
"text": [
"IgG1"
],
"offsets": [
[
907,
911
]
],
"normalized": []
},
{
"id": "PMID-19236257_T1000",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
453,
461
]
],
"normalized": []
},
{
"id": "PMID-19236257_T1001",
"type": "Organism",
"text": [
"patients"
],
"offsets": [
[
1066,
1074
]
],
"normalized": []
},
{
"id": "PMID-19236257_T30",
"type": "Protein_domain_or_region",
"text": [
"Fc fragment"
],
"offsets": [
[
892,
903
]
],
"normalized": []
},
{
"id": "PMID-19236257_T17",
"type": "Gene_or_gene_product",
"text": [
"antibodies to VEGF"
],
"offsets": [
[
525,
543
]
],
"normalized": []
},
{
"id": "PMID-19236257_T19",
"type": "Gene_or_gene_product",
"text": [
"VEGFR-2"
],
"offsets": [
[
598,
605
]
],
"normalized": []
},
{
"id": "PMID-19236257_T20",
"type": "Gene_or_gene_product",
"text": [
"antibodies to the extracellular domain of VEGFR-1"
],
"offsets": [
[
545,
594
]
],
"normalized": []
},
{
"id": "PMID-19236257_T33",
"type": "Pathological_formation",
"text": [
"cancer"
],
"offsets": [
[
182,
188
]
],
"normalized": []
},
{
"id": "PMID-19236257_T36",
"type": "Pathological_formation",
"text": [
"cancer"
],
"offsets": [
[
446,
452
]
],
"normalized": []
},
{
"id": "PMID-19236257_T37",
"type": "Pathological_formation",
"text": [
"cancer"
],
"offsets": [
[
1059,
1065
]
],
"normalized": []
}
] | [
{
"id": "PMID-19236257_E14",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
489,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E15"
},
{
"role": "Cause",
"ref_id": "PMID-19236257_T17"
}
]
},
{
"id": "PMID-19236257_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibiting"
],
"offsets": [
[
51,
61
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E9"
},
{
"role": "Cause",
"ref_id": "PMID-19236257_T6"
}
]
},
{
"id": "PMID-19236257_E2",
"type": "Regulation",
"trigger": {
"text": [
"Aberrant"
],
"offsets": [
[
135,
143
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E10"
}
]
},
{
"id": "PMID-19236257_E3",
"type": "Regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
258,
266
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E10"
}
]
},
{
"id": "PMID-19236257_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"Inhibition"
],
"offsets": [
[
386,
396
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E13"
}
]
},
{
"id": "PMID-19236257_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
489,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E15"
},
{
"role": "Cause",
"ref_id": "PMID-19236257_T20"
}
]
},
{
"id": "PMID-19236257_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
489,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E15"
},
{
"role": "Cause",
"ref_id": "PMID-19236257_T19"
}
]
},
{
"id": "PMID-19236257_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
489,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E15"
}
]
},
{
"id": "PMID-19236257_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
489,
496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "PMID-19236257_E15"
},
{
"role": "Cause",
"ref_id": "PMID-19236257_T25"
}
]
},
{
"id": "PMID-19236257_E9",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
69,
81
]
]
},
"arguments": [
{
"role": "AtLoc",
"ref_id": "PMID-19236257_T4"
}
]
},
{
"id": "PMID-19236257_E10",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenesis"
],
"offsets": [
[
144,
156
]
]
},
"arguments": []
},
{
"id": "PMID-19236257_E11",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
282,
292
]
]
},
"arguments": []
},
{
"id": "PMID-19236257_E12",
"type": "Blood_vessel_development",
"trigger": {
"text": [
"angiogenic"
],
"offsets": [
[
365,
375
]
]
},
"arguments": []
},
{
"id": "PMID-19236257_E13",
"type": "Pathway",
"trigger": {
"text": [
"pathway"
],
"offsets": [
[
311,
318
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19236257_T10"
}
]
},
{
"id": "PMID-19236257_E15",
"type": "Pathway",
"trigger": {
"text": [
"pathway"
],
"offsets": [
[
506,
513
]
]
},
"arguments": [
{
"role": "Participant",
"ref_id": "PMID-19236257_T16"
}
]
}
] | [
{
"id": "PMID-19236257_1",
"entity_ids": [
"PMID-19236257_T1",
"PMID-19236257_T2"
]
}
] | [
{
"id": "PMID-19236257_R1",
"type": "frag",
"arg1_id": "PMID-19236257_T19",
"arg2_id": "PMID-19236257_T20",
"normalized": []
}
] |
End of preview. Expand
in Dataset Viewer.
Dataset Card for MLEE
MLEE is an event extraction corpus consisting of manually annotated abstracts of papers on angiogenesis. It contains annotations for entities, relations, events and coreferences The annotations span molecular, cellular, tissue, and organ-level processes.
Citation Information
@article{pyysalo2012event,
title={Event extraction across multiple levels of biological organization},
author={Pyysalo, Sampo and Ohta, Tomoko and Miwa, Makoto and Cho, Han-Cheol and Tsujii, Jun'ichi and Ananiadou, Sophia},
journal={Bioinformatics},
volume={28},
number={18},
pages={i575--i581},
year={2012},
publisher={Oxford University Press}
}
- Downloads last month
- 41