cisplatin

etoposide

cytarabine

cyclophosphamide

Bcl-2 expression correlates with apoptosis induction but not tumor growth delay in transplantable murine lymphomas treated with different chemotherapy drugs. Previously, we have reported that the bcl-2-expressing murine lymphoma cell line LY-ar is resistant to chemotherapy-induced apoptosis when compared to the non-bcl-2-expressing LY-as cell line. The intent of the present study was to determine whether this relationship extends to lymphomas produced from these cell lines in syngeneic mice, after treatment with the same chemotherapy agents. ### methods LY-ar and LY-as tumors were grown in the hind legs of syngeneic mice. They were subsequently exposed to graded doses of cisplatin ( CP ) , etoposide ( VP-16 ) , Adriamycin ( ADR ) , cytarabine ( ara-C ) , cyclophosphamide ( CY ) , or camptothecin ( CAM ) . Apoptotic bodies were scored in histological sections of tumors that had been stained with hematoxylin and eosin. Tumor growth delay was determined on tumors that were treated when they were 8 mm in diameter. Thereafter, tumor diameter was measured daily with a vernier caliper until they had grown to a maximum of 16 mm in diameter. ### results When transplanted into host animals, tumors derived from these two cell lines and treated in vivo with CP, VP-16, ADR, ara-C, CY, and CAM displayed apoptotic propensities similar to those seen in the same cell lines when treated in vitro. Generally, for all the drugs tested, apoptotic indices in LY-as tumors were significantly higher than in LY-ar tumors. However, tumor growth delay measurements could not be predicted with any accuracy from the apoptotic indices. For some drugs LY-ar tumors were more sensitive than LY-as tumors (CP, Vp-16, ADR, ara-C), yet LY-ar tumors were more resistant to CY. ### conclusions Despite considerable interest in using apoptotic indices as predictors of treatment outcome, the data presented here suggest that these relationships are very complex. This may be especially true for chemotherapy agents for which effects in vivo are complicated by pharmacokinetics, host effects, and tumor cell heterogeneity.


capecitabine

oxaliplatin

Gastric cancer with para-aortic lymph node metastases: do not miss a chance of cure! This letter to editor is a comment to the paper by Wang et al. entitled: "A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis". In a phase II trial , patients with primary gastric cancer and clinical involvement of para-aortic nodes ( PAN ) were treated by neo-adjuvant chemotherapy with capecitabine and oxaliplatin combination , and responders were then submitted to gastrectomy with D2 lymphadenectomy . The diagnostic and therapeutic approach adopted in this protocol is discussed, with special reference to the potential limits of computed tomography scan for the clinical diagnosis of PAN metastases (false positive results), and the opportunity to perform a D2 plus para-aortic lymphadenectomy, to further increase the chance of cure in patients with suspected PAN metastases.


palbociclib

ribociclib

abemaciclib

Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. The development and approval of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer represents a major milestone in cancer therapeutics. Three different oral CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have significantly improved progression-free survival by a number of months when combined with endocrine therapy. More recently, improvement in overall survival has been reported with ribociclib and abemaciclib. The toxicity profile of all three drugs is well described and generally easily manageable with dose reductions when indicated. More myelotoxicity is observed with palbociclib and ribociclib , but more gastrointestinal toxicity is observed with abemaciclib . Emerging data is shedding light on the resistance mechanisms associated with CDK4/6 inhibitors, including cell cycle alterations and activation of upstream tyrosine kinase receptors. A number of clinical trials are exploring several important questions regarding treatment sequencing, combinatorial strategies, and the use of CDK4/6 inhibitors in the adjuvant and neoadjuvant settings, thereby further expanding and refining the clinical application of CDK4/6 inhibitors for patients with breast cancer.


bupivacaine

tramadol

Subarachnoid morphine, bupivacaine and fentanyl as part of combined spinal-epidural analgesia for low anterior resection. A prospective, randomised, double-blind clinical trial. This study was designed to compare the efficacy of subarachnoid morphine alone or in combination with bupivacaine and fentanyl for combined spinal-epidural analgesia in colorectal surgery. This is a prospective, randomised, double-blind clinical trial. Sixty patients undergoing low anterior resection were assigned to one of three groups: subarachnoid morphine, bupivacaine and fentanyl, subarachnoid morphine and bupivacaine or subarachnoid morphine only. Epidural catheter placement and subarachnoid injection were done via a combined spinal-epidural Epistar needle at L2-3. The epidural catheter was used for scheduled intraoperative bupivacaine and intermittent postoperative bupivacaine and morphine administration. Intraoperative epidural bupivacaine , intraoperative intravenous fentanyl use , time to first analgesia request , postoperative visual analogue scale pain scores , tramadol requirements and side-effects were recorded for 72 hours . Postoperative analgesia was comparable in all groups. Intraoperative fentanyl and bupivacaine consumption was lowest in the morphine, bupivacaine and fentanyl group. Time to first analgesia request was longer in the morphine, bupivacaine and fentanyl compared to the morphine group (P = 0.009). tramadol use was lower in the morphine and bupivacaine group compared to morphine, bupivacaine and fentanyl (P = 0.017) on postoperative day two. There were no significant adverse effects. All patients ambulated the morning after surgery. The addition of bupivacaine and fentanyl to subarachnoid morphine did not confer any advantage on postoperative visual analogue scale scores and tramadol use, but lowered the need for additional intraoperative intravenous fentanyl and epidural bupivacaine and prolonged the time to first analgesia request.


bevacizumab

ranibizumab

Intravitreal Anti Vascular Endothelial Growth Factor Agents in The Management of Retinal Diseases: An Audit. The study aimed to describe our initial experience with the use of anti vascular endothelial growth factors (anti-VEGFs) in the treatment of retinal diseases. ### methods The case records of all patients who had received at least 3 doses of intravitreal anti- VEGF injections between January 2012 to December 2016 were reviewed. Information culled from the data was age, sex, indications for treatment, type of injection, presenting visual acuity, post injection visual acuity, systemic and ocular co morbidities. Results were analyzed using Statistical Package for Social Sciences (SPSS) 20.0 for Windows statistical software. ### results A total of 190 injections were given during the study period, to 58 eyes of 50 patients. Twenty-eight females (56.00%) and twenty-two males (44.00%) were seen with a mean age of 59.6± 11.66. bevacizumab was the most frequently administered anti- VEGF, 142 (74.74%) while only 48(25.26%) injections of ranibizumab were given. Three eyes had both bevacizumab and ranibizumab ( 1.58 % ) . Retinal vein occlusion 61(32.11%) was the commonest indication for the injections followed by diabetic macular edema 43(22.63%) and proliferative diabetic retinopathy 42(22.11%). Others were neovascular age related macular degeneration, neovascular glaucoma, vitreous hemorrhage, myopic choroidal neovascularization and cystoid macular edema. There was an association between age and disease, (p = 0.001). There was an improvement in visual acuity after intervention in cases with retinal vein occlusion and diabetic macular edema, and this was statistically significant. Hypertension was the commonest systemic disorder in this series 81(42.36%) and the supero-temporal quadrant 131(68.95%) was the most preferred position to administer the injection. Floaters was the commonest complication seen. ### conclusion Anti VEGFs have become an invaluable tool in the management of a number of retinal diseases in our center. However, the cost implications are a hindrance to an increased uptake of this form of treatment. Cheaper alternative preparations should be made available to encourage the uptake. Government in developing countries should be encouraged to bear the health burden of the old aged pensioner (OAP).


etoposide

prednisone

vincristine

cyclophosphamide

doxorubicin

rituximab

Successful Use of EPOCH-R in 2 Young Adult Patients With Burkitt Lymphoma and Acute Kidney Injury: A Case Report. Pediatric Burkitt lymphoma has historically been treated with intensive methotrexate-based chemotherapy, which improves patient survival while causing severe toxicities. Young patients typically have better outcomes with intensive therapies, while adults and immunocompromised patients have higher toxicities and worse outcomes. Newer treatment regimens , including etoposide , prednisone , vincristine , cyclophosphamide , doxorubicin , rituximab ( EPOCH-R ) , show promise for these patients . However, few studies exist to demonstrate efficacy and improved toxicity profile with EPOCH-R. We present 2 cases: a 25-year-old male with Down syndrome and an 18-year-old male with Burkitt lymphoma and significant renal injury who were successfully treated with EPOCH-R with minimal toxicities.


propranolol

atropine

Effect of scorpion Leiurus quinquestriatus (H&E) venom on rat's heart rate and blood pressure. The effects of scorpion Leiurus quinquestriatus (H&E) venom collected from the South Sinai region, Egypt, on heart rate (HR) and mean arterial pressure (MAP) were studied after intramuscular administration of 3 different doses (100, 200 and 400 micrograms/kg) to anesthetized rats. The effects of adrenergic and cholinergic blocking agents on the venom-induced HR and MAP changes were also evaluated. In two groups of rats , propranolol or atropine were given before the venom administration . In the third group the venom was given before the injection of propranolol and atropine in combination. HR was measured by using a cardiotachometer coupler connected to an ECG coupler. MAP was calculated from the recorded arterial blood pressure (ABP) after catheterization of the left common carotid artery. Venom doses of 100 and 200 micrograms/kg produced tachycardia with a dose-response relationship, whereas 400 micrograms/kg evoked sinus tachycardia followed by bradycardia then tachycardia. MAP was elevated after the administration of each dose and reached its maximum value after 60 min with a dose-response relationship. Sinus, atrial and ventricular arrhythmias were observed from the recorded ECG during the time studied. This study revealed that the venom has pressor and depressor effects which are mediated through the autonomic nervous system. propranolol reduced the stimulatory effects of the highest dose of the venom while atropine was effective in eliminating the depressor effect of the venom on HR. The arrhythmias induced by the venom were blocked by the injection of the two blockers and are assumed to be due to the release of catecholamines and acetylcholine.


Doxycycline

azithromycin

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin. Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility . This model makes possible the study of both short- and long-term outcomes of chlamydial infection.


amantadine

reserpine

reserpine

alpha-methyl-p-tyrosine

Effect of amantadine on pupillary diameter in mice. amantadine, injected into mice, produces dose-dependent mydriasis. The pupillary dilation caused by amantadine is not abolished by pretreatment with reserpine , or by combined pretreatment with reserpine and alpha-methyl-p-tyrosine , although the mydriasis is reduced by approximately 25 % . Thus, release of catecholamines from nerve terminals can account for only 25% of amantadine-produced mydriasis. haloperidol and phentolamine can partially block the effect of amantadine, but, when given after reserpine, neither of the antagonists increases the blockade produced by reserpine alone. We conclude that the catecholaminergic system contributes only partially to the pupillary effect of amantadine, and that other mechanisms appear to be involved.


curcumin

etoposide

Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species. curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34(+) cells, and granulocytes were incubated for 4 or 24 hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23 days and etoposide was administered for the final 3 days of the experiment . curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34(+) cells and granulocytes. curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l-cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P<0.05) and induced apoptosis of BNML cells more efficiently than etoposide alone (1.54-fold change versus etoposide alone; P<0.05), but this treatment protected nonleukemic B-cells from apoptosis. Thus, curcumin can increase the antileukemic effect of etoposide through reactive oxygen species in sensitive myeloid leukemia cells, and it is harmless to normal human cells.


Mitomycin

Vinorelbine

Cisplatin

Combination Chemotherapy with Mitomycin C , Vinorelbine , and Cisplatin ( MVrP ) in Patients with Advanced Non-Small Cell Lung Cancer . A phase II study was conducted in patients with advanced non-small cell lung cancer (NSCLC) in order to evaluate the efficacy and toxicity of the combination chemotherapy regimen of mitomycin C, vinorelbine, and cisplatin (MVrP). ### Materials And Methods Between June 1996 and December 2000, fifty-nine patients with unresectable stage IIIB to IV, pathologically documented NSCLC were enrolled in this study. One cycle consisted of mitomycin C 10 mg/m2 i.v. day 1, vinorelbine 30 mg/m2 i.v. days 1 & 15, and cisplatin 80 mg/m2 i.v day 1 and the next cycle consisted of vinorelbine 30 mg/m2 i.v. days 29 & 43, and cisplatin 80 mg/m2 i.v day 29. Each cycle was alternated and treatments were repeated every 8 weeks. ### results We were able to evaluate fifty-three of 59 patients. Objective responses were seen in 22 (41.5%) patients (CR 0%, PR 41.5%). The median duration of response was 13.7 weeks and the median time to progression was 17.7 weeks. The median overall survival was 45.6 weeks. There was a significantly longer survival seen in responders (p=0.041). The toxicities of this regimen were acceptable without treatment related toxic death. ### conclusion This study suggests that a combination regimen of mitomycin C, vinorelbine, and cisplatin is relatively effective and well tolerated for the treatment of advanced NSCLC.


amoxicillin

gentamicin

Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch. The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin ( 15 mg/kg body wt/48 h ) and/or gentamicin ( 4 mg/kg body wt/day ) administered as intramuscular ( i.m . ) injections . Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.


chloroquine

lopinavir

hydroxychloroquine

azithromycin

favipiravir

ribavirin

darunavir

remdesivir

Tissue distributions of antiviral drugs affect their capabilities of reducing viral loads in COVID-19 treatment. Repurposing of approved antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising strategy to treat Coronavirus disease 2019 (COVID-19) patients. Previously we reported our hypothesis that the antiviral drugs with high lung distributions might benefit COVID-19 patients by reducing viral loads. So far , chloroquine , lopinavir , hydroxychloroquine , azithromycin , favipiravir , ribavirin , darunavir , remdesivir , and umifenovir have been tested in COVID-19 clinical trials . Here we validated our hypothesis by comparing the pharmacokinetics profiles of these drugs and their capabilities of reducing viral load in clinical trials. According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (TMPRSS2) makes the lung and intestine vulnerable to SARS-CoV-2. Hydroxychloroquine, chloroquine, and favipiravir, which were highly distributed to the lung, were reported to reduce viral loads in respiratory tract of COVID-19 patients. Conversely, drugs with poor lung distributions, including lopinavir/ritonavir, umifenovir and remdesivir, were insufficient to inhibit viral replication. lopinavir/ritonavir might inhibit SARS-CoV-2 in the GI tract according to their distribution profiles. We concluded here that the antiviral drugs should be distributed straight to the lung tissue for reducing viral loads in respiratory tract of COVID-19 patients. Additionally, to better evaluate antiviral effects of drugs that target the intestine, the stool samples should also be collected for viral RNA test in the future.


bicalutamide

flutamide

nilutamide

Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer. Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens , bicalutamide offers some advantages over flutamide as it possesses a much longer half-life , allowing a once daily regimen , and has advantages over nilutamide in terms of fewer adverse effects .


vinblastine

methotrexate

Vinblastine and methotrexate for advanced bladder cancer.  Fifty-seven patients with advanced measurable urothelial tract cancer , 52 of whom had an adequate trial , were treated weekly with 3 to 4 mg . per m.2 vinblastine and 30 to 40 mg . per m.2 methotrexate . Of 3 patients with unidimensional parameters 2 showed improvement lasting 16 and 27 months, which was documented by serial cystoscopic examinations. An additional 2 patients had measurable disease that could have been encompassed in a preoperative radiotherapy field. Both patients are free of disease at more than 12 and 14 months, respectively. Of the 47 patients with bidimensionally measurable parameters 19 (40 per cent) achieved a complete or partial remission lasting a median of 8 months, with a range of 1 to 24 months. Of 25 patients with intra-abdominal or pelvic disease 7 achieved a complete or partial remission and 5 also had a minor remission. Of note, 18 of 38 patients who had received no prior chemotherapy achieved a remission versus 1 of 9 who had been treated previously (p equals 0.06). Responders frequently obtained another remission with subsequent chemotherapy (4 of 9 versus 0 of 16, p equals 0.03). Responders lived 14 months versus 8 months for nonresponders (p equals 0.02). Four responders had brain metastases compared to none of 28 nonresponders. The combination of vinblastine and methotrexate is a well tolerated, effective outpatient regimen for patients with urothelial tract cancers.


bombesin

somatostatin

Inhibition of neurally mediated gastrin secretion by bombesin antiserum. In vitro studies on the vascularly perfused rat stomach have shown that gastrin secretion is regulated by intramural cholinergic and noncholinergic neurons. We have postulated that bombesin (gastrin-releasing peptide), a known gastrin stimulant present in antral mucosal nerve fibers, is the most likely candidate for noncholinergic transmitter. bombesin antiserum (final dilution, 1:150) but not control serum added to the vascular perfusate inhibited the gastrin response to 1,1-dimethyl-4-phenylpiperazinium by 59 +/- 17% (P less than 0.01) and to electrical field stimulation by 60 +/- 16% (P less than 0.01), and its effect was additive to that of 10(-7) M atropine (75-94%), thus accounting for the greater part of neurally induced gastrin secretion. The effects of atropine and bombesin antiserum on somatostatin secretion were consistent also with blockade of cholinergic and noncholinergic neurons, respectively. The results indicate that bombesin and acetylcholine are the main intramural neural regulators of gastrin and somatostatin secretion . Acetylcholine acts predominantly to decrease the paracrine secretion of somatostatin, thereby eliminating the continuous restraint of somatostatin on gastrin secretion and enabling bombesin to exert its potent stimulatory effect on gastrin secretion.


resveratrol

meclofenamic acid

zeaxanthin

Resveratrol protects human retinal pigment epithelial cells from acrolein-induced damage. Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells. ### methods Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells. ### results Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid . Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment. ### conclusions Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.


clindamycin

lincomycin

clindamycin

Antibiotic susceptibilities of streptococci from the mouth and blood of patients treated with penicillin or lincomycin and clindamycin. Patients undergoing dental extractions were non-randomly allocated to three groups, one of which received no antibiotic, one benzylpenicillin followed by oral penicillin for 5 days, and the third intramuscular lincomycin followed by oral clindamycin. Dental extraction was performed at the beginning of the course of chemotherapy. Streptococci were isolated from the extracted teeth, from blood cultures collected before and immediately after dental extraction, and from sutures removed from the gums 5-7 days after the operation. The species of these organisms was determined, and their susceptibilities to penicillin, clindamycin, cephaloridine, erythromycin and tetracycline were assessed. The majority of streptococci isolated from teeth belonged to the species Streptococcus sanguis, S. mitior, S. mutans and S. milleri. Occasional isolates of each of these organisms collected before the antibiotic could take effect were resistant to penicillin. Three of these species, but not S. mutans, were the commonest streptococci to be isolated from the blood after dental extraction. Penicillin completely suppressed dental bacteriaemia under the conditions of our investigation, and lincomycin reduced the incidence by about 60 per cent. The commonest streptococci from sutures were also S. sanguis, S. mitior, S. mutans and S. milleri. S. faecalis was also isolated, but only in patients who had received antibiotics. Among the non-faecalis organisms , penicillin resistance was significantly more frequent among isolates from patients given penicillin than from patients not given this antibiotic , and clindamycin resistance was significantly more frequent among isolates from patients given lincomycin and clindamycin than from patients not given these antibiotics .


erlotinib

crizotinib

[Patient's beliefs about oral targeted therapies and impact on drug adherence in lung cancer: A pilot prospective study]. Oral targeted therapies are a new option for lung cancer treatment. However, patient's belief about these drugs - which may interact with adherence - is poorly known in this setting. ### method Our study is a pilot prospective unicentric study. Inclusion criteria were: to have been diagnosed with a lung cancer; and to be prescribed with an oral targeted therapy in second line or more. The main objective was to assess patient's specific (SB) and general beliefs (GB) about these drugs according to the Beliefs about Medicines Questionnaire (BMQ). The declared adherence was assessed with the Morisky's test. All included patients underwent a semi-structured interview with a psychologist. ### results Fifthteen patients were included : 12 underwent erlotinib treatment and 3 a crizotinib treatment . The mean score (±standard deviation) at BMQ was 54/85 (±6) overall; 34/50 (±5) for specific belief and 19/35 (±3) for general belief about drugs. During interview, 47% believed in efficacy of targeted oral therapy; 93% reported concerns about their drug; 80% considered that the information given by the physician about the drug was comprehensive; but 40% still required additional information about it. The mean score at Morisky's test was 3/4 (±2) and 53% reported to have forgotten at least once their antineoplastic drug. No correlation was found between belief and adherence. ### conclusion Belief about t anti-cancer targeted oral therapy is relatively fair but adherence is moderate in this pilot study. Interview shows the need for additional information about the prescribed drug.


trastuzumab

paclitaxel

Taxol

Immunotherapy: new options in breast cancer treatment. Immunotherapy is a promising new approach in breast cancer treatment, complementing surgery, chemotherapy, radiation and antihormonal therapy. Primarily, two treatment options are available which are supported by a rapidly growing body of clinical evidence. These are active specific immunotherapy with Theratope and passive immunotherapy targeting the HER-2 receptor with trastuzumab (Herceptin). trastuzumab has a proven efficacy as monotherapy as well as in combination with chemotherapeutic agents in HER-2-overexpressing metastatic breast cancer. trastuzumab is generally well tolerated although cardiotoxicity has been observed, especially when in combination with doxorubicin (Adriamycin), where this can be a serious concern. Therefore, less cardiotoxic combinations with docetaxel (Taxotere), vinorelbine (Navelbine) and epirubicin (Pharmorubicin) or cyclophosphamide (Endoxana) have been tested. The combination of trastuzumab with paclitaxel ( Taxol ) is well approved . The use of trastuzumab in adjuvant and preoperative therapy is currently being examined in controlled trials. After a brief outline of immunotherapy with Theratope and trastuzumab, this article reviews recent and ongoing clinical studies conducted with trastuzumab.


cyclosporin

cyclophosphamide

corticosteroids

[Anti-MDA5 (melanoma differentiation-associated gene 5) antibody and dermatomyositis with rapidly progressive interstitial pneumonia]. Anti-MDA5 antibody is one of the dermatomyositis-specific autoantibodies and anti-MDA5-potsitive patients show characteristic clinical features, such as hypomyositis, high prevalence of acute/subacute interstitial pneumonia (A/SIP) with poor prognosis, hyperferritinemia and elevated hepatobiliary enzyme. We found that serum IL-6, IL-18, M-CSF and IL-10 were significantly higher and serum IL-12 and IL-22 were significantly lower in anti-MDA5-positive patients than in anti-MDA5-negative patients before treatment. Taking together these serological findings, we hypothesized that monocyte and macrophage activation may underlie in the pathophysiology of anti-MDA5-positive patients. They rarely survive after they become to need oxygenation, and so need to be treated as soon as possible once the diagnosis has been made. Intensive regimen of combined immunosuppressive therapy ( high-dose corticosteroids , oral cyclosporin and intravenous cyclophosphamide ( IVCY , 900 - 1000 mg/m(2 ) in every other week ) ) improved the survival rate of anti-MDA5-positive patients . Especially, the serum ferritin levels tended to go down about 14 days after IVCY, suggesting that IVCY might be a key drug in the treatment of anti-MDA5-positive A/SIP patients.


Bortezomib

Panobinostat

MicroRNAs as possible indicators of drug sensitivity in breast cancer cell lines. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. In this way they might influence whether a cell is sensitive or resistant to a certain drug. So far, only a limited number of relatively small scale studies comprising few cell lines and/or drugs have been performed. To obtain a broader view on miRNAs and their association with drug response, we investigated the expression levels of 411 miRNAs in relation to drug sensitivity in 36 breast cancer cell lines. For this purpose IC50 values of a drug screen involving 34 drugs were associated with miRNA expression data of the same breast cancer cell lines. Since molecular subtype of the breast cancer cell lines is considered a confounding factor in drug association studies, multivariate analysis taking subtype into account was performed on significant miRNA-drug associations which retained 13 associations. These associations consisted of 11 different miRNAs and eight different drugs (among which paclitaxel, docetaxel and veliparib). The taxanes, paclitaxel and docetaxel, were the only drugs having miRNAs in common: hsa-miR-187-5p and hsa-miR-106a-3p indicative of drug resistance while paclitaxel sensitivity alone associated with hsa-miR-556-5p. tivantinib was associated with hsa-let-7d-5p and hsa-miR-18a-5p for sensitivity and hsa-miR-637 for resistance. Drug sensitivity was associated with hsa-let-7a-5p for Bortezomib , hsa-miR-135a-3p for JNJ-707 and hsa-miR-185 - 3p for Panobinostat . Drug resistance was associated with hsa-miR-182-5p for veliparib and hsa-miR-629-5p for Tipifarnib. Pathway analysis for significant miRNAs was performed to reveal biological roles, aiding to find a potential mechanistic link for the observed associations with drug response. By doing so hsa-miR-187-5p was linked to the cell cycle G2-M checkpoint in line with this checkpoint being the target of taxanes. In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this context.


regorafenib

lenvatinib

Interstitial pneumonia suspected during regorafenib administration and exacerbated by subsequent therapy with lenvatinib for unresectable hepatocellular carcinoma. Recently, three tyrosine kinase inhibitors (TKIs) have become available for treatment of unresectable hepatocellular carcinoma (HCC). We herein report a case of a 59-year-old man with interstitial pneumonia that was suspected during regorafenib administration and was exacerbated by subsequent lenvatinib treatment for advanced HCC. After sorafenib was discontinued due to progressive HCC, regorafenib treatment was started. Progressive HCC was again noted and reticular shadows were suspected in both lower lung fields at 2 months after starting regorafenib administration. Subsequent treatment with lenvatinib obtained a partial response for HCC, but the reticular shadows became marked and dyspnea on effort emerged, followed by hypoxemia and an increased Krebs von den Lungen-6 (KL-6) value. Because we suspected acute interstitial pneumonia, due to these TKIs, intravenous pulse steroid therapy was started immediately after discontinuing lenvatinib. Within 1 week after starting steroid therapy, the patient's respiratory condition and hypoxemia gradually began improving. No previous case of pulmonary interstitial changes that appeared in association with regorafenib administration for HCC and that were exacerbated by subsequent treatment with lenvatinib has been reported . This case emphasizes that it is necessary to observe the patient's respiratory condition and to perform imaging examinations to monitor for adverse events during TKI treatment.


doxycycline

ceftriaxone

amoxicillin

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis. The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline , ceftriaxone , or amoxicillin for 28 days . Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.


olaparib

abiraterone

abiraterone

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Patients with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations have a better response to treatment with the poly(ADP-ribose) polymerase inhibitor olaparib than patients without HRR mutations. Preclinical data suggest synergy between olaparib and androgen pathway inhibitors. We aimed to assess the efficacy of olaparib plus the androgen pathway inhibitor abiraterone in patients with metastatic castration-resistant prostate cancer regardless of HRR mutation status. ### methods We carried out this double-blind, randomised, placebo-controlled phase 2 trial at 41 urological oncology sites in 11 countries across Europe and North America. Eligible male patients were aged 18 years or older with metastatic castration-resistant prostate cancer who had previously received docetaxel and were candidates for abiraterone treatment. Patients were excluded if they had received more than two previous lines of chemotherapy, or had previous exposure to second-generation antihormonal drugs. Patients were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive oral olaparib 300 mg twice daily or placebo. All patients received oral abiraterone 1000 mg once daily and prednisone or prednisolone 5 mg twice daily. Patients and investigators were masked to treatment allocation. The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS; based on Response Evaluation Criteria in Solid Tumors version 1.1 and Prostate Cancer Clinical Trials Working Group 2 criteria). Efficacy analyses were done in the intention-to-treat population, which included all randomly assigned patients, and safety analyses included all patients who received at least one dose of olaparib or placebo. This trial is registered with ClinicalTrials.gov, number NCT01972217, and is no longer recruiting patients. ### findings Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. Of those, 142 patients were randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). The clinical cutoff date for the final analysis was Sept 22, 2017. Median rPFS was 13·8 months (95% CI 10·8-20·4) with olaparib and abiraterone and 8·2 months (5·5-9·7) with placebo and abiraterone (hazard ratio [HR] 0·65, 95% CI 0·44-0·97, p=0·034). The most common grade 1-2 adverse events were nausea (26 [37%] patients in the olaparib group vs 13 [18%] patients in the placebo group), constipation (18 [25%] vs eight [11%]), and back pain (17 [24%] vs 13 [18%]). 38 (54%) of 71 patients in the olaparib and abiraterone group and 20 (28%) of 71 patients in the placebo and abiraterone group had grade 3 or worse adverse events, including anaemia (in 15 [21%] of 71 patients vs none of 71), pneumonia (four [6%] vs three [4%]), and myocardial infarction (four [6%] vs none). Serious adverse events were reported by 24 ( 34 % ) of 71 patients receiving olaparib and abiraterone ( seven of which were related to treatment ) and 13 ( 18 % ) of 71 patients receiving placebo and abiraterone ( one of which was related to treatment ) . One treatment-related death (pneumonitis) occurred in the olaparib and abiraterone group. ### interpretation olaparib in combination with abiraterone provided clinical efficacy benefit for patients with metastatic castration-resistant prostate cancer compared with abiraterone alone. More serious adverse events were observed in patients who received olaparib and abiraterone than abiraterone alone. Our data suggest that the combination of olaparib and abiraterone might provide an additional clinical benefit to a broad population of patients with metastatic castration-resistant prostate cancer. ### funding AstraZeneca.


propranolol

labetalol

prazosin

Blood pressure lowering action and alpha-adrenolytic effect of adimolol in rats. Adimolol is a new antihypertensive agent with strong nonselective beta- and moderate alpha-adrenolytic properties. In order to elucidate whether the alpha-adrenoceptor blockade by adimolol may contribute to the blood pressure lowering action of the compound, we tested 1) the effect on heart rate and blood pressure in conscious spontaneously hypertensive rats after oral administration and 2) the influence on the pressor effect of intra-arterially injected noradrenaline in autoperfused rat hindquarters after i.v. administration. Adimolol was compared with propranolol, labetalol, prazosin and combinations of propranolol plus low-dose prazosin. In conscious spontaneously hypertensive rats, labetalol, propranolol plus low-dose prazosin and adimolol lowered blood pressure considerably in parallel with heart rate. propranolol alone acutely lowered heart rate, but not blood pressure. Low-dose prazosin alone lowered blood pressure and heart rate only moderately. In autoperfused hindquarters , the pressor-response curve to noradrenaline was dose-dependently shifted to the left by propranolol and to the right by labetalol or prazosin . The leftward shift by propranolol could be antagonized dose-dependently by addition of low doses of prazosin. Adimolol, at doses of 0.1, 10 and 20 mg/kg, did not significantly influence the pressor-response curve to noradrenaline in this model, whereas a slight but significant shift to the left was observed with 1 mg/kg. In summary, the cardiovascular effects of adimolol in rats cannot completely be explained by beta-adrenoceptor blockade. They can be mimicked by the concomitant administration of a beta-adrenoceptor blocking and an alpha-adrenoceptor blocking agent. We conclude that the alpha-adrenolytic activity of adimolol can be demonstrated in vivo and may contribute to the blood pressure lowering action of the compound in rats.


Rivastigmine

Donepezil

Pharmacotherapies for Parkinson's disease symptoms related to cholinergic degeneration. Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion : Rivastigmine , a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase , is effective for dementia , whereas the use of Donepezil is still in the realm of investigation . Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.


methotrexate

cyclophosphamide

vincristine

doxorubicin

etoposide

dexamethasone

[Burkitt's lymphoma occurring as a primary lymphomatous effusion]. A 39-year-old man was admitted with massive ascites. Specimens of ascitic fluid contained numerous cells with a FAB-L3 appearance, and small noncleaved cell lymphoma morphology. These cells expressed CD10, CD19, CD20, CD38, CD45, HLA-DR, and IgM antigens, and were positive for IgM and c-myc protein in cytoplasmic immunostaining tests. Clonal rearrangements of IgH and c-myc genes were detected by Southern blot analysis. No mass lesions were found by physical examination, and systemic computed photography did not reveal enlargement of lymph nodes, spleen, or liver. Bone marrow aspiration showed no infiltration of malignant cells. Ga scintigraphy indicated hot lesions only in the abdomen. These findings suggested that Burkitt's lymphoma had developed in the peritoneal cavity as a primary lymphomatous effusion. Chemotherapy with methotrexate , cyclophosphamide , vincristine , doxorubicin , etoposide , and dexamethasone was effective , and the patient has been free from the disease for 1 year since completion of consolidation treatment with autologous peripheral blood stem cell transplantation .


etoposide

doxorubicin

A(2B) and A(3) adenosine receptors modulate vascular endothelial growth factor and interleukin-8 expression in human melanoma cells treated with etoposide and doxorubicin. Cancer patients undergoing treatment with systemic cancer chemotherapy drugs often have abnormal growth factor and cytokine profiles. Thus, serum levels of interleukin-8 (IL-8) are elevated in patients with malignant melanoma. In addition to IL-8, aggressive melanoma cells secrete, through its transcriptional regulator hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor (VEGF), which promotes angiogenesis and metastasis of human cancerous cells. Whether these responses are related to adenosine, a ubiquitous mediator expressed at high concentrations in cancer and implicated in numerous inflammatory processes, is not known and is the focus of this study. We have examined whether the DNA-damaging agents etoposide ( VP-16 ) and doxorubicin can affect IL-8 , VEGF , and HIF-1 expressions in human melanoma cancer cells . In particular, we have investigated whether these responses are related to the modulation of the adenosine receptor subtypes, namely, A(1), A(2A), A(2B), and A(3). We have demonstrated that A(2B) receptor blockade can impair IL-8 production, whereas blocking A(3) receptors, it is possible to further decrease VEGF secretion in melanoma cells treated with VP-16 and doxorubicin. This understanding may present the possibility of using adenosine antagonists to reduce chemotherapy-induced inflammatory cytokine production and to improve the ability of chemotherapeutic drugs to block angiogenesis. Consequently, we conclude that adenosine receptor modulation may be useful for refining the use of chemotherapeutic drugs to treat human cancer more effectively.


tamsulosin

meloxicam

The effect of combined therapy with tamsulosin hydrochloride and meloxicam in patients with benign prostatic hyperplasia symptoms and impact on nocturia and sleep quality . We aimed to compare the effect and feasibility of a combined therapy with tamsulosin hydrochloride plus meloxicam, and tamsulosin hydrochloride alone in patients with benign prostate hyperplasia symptoms and impact on nocturia and sleep quality. ### Materials And Methods Four hundred male patients were included in this study between 2008 and 2011. Patients were randomly divided into two groups: one received tamsulosin hydrochloride 0.4 mg (Group 1, 200 patients) and the other tamsulosin hydrochloride 0.4 mg plus meloxicam 15 mg (Group 2, 200 patients) prospectively. Patients were evaluated for benign prostate hyperplasia (BPH) symptoms according to the American Urological Association clinical guidelines and sleep quality according to Pittsburgh Sleep Quality Index (PSQI). Patients were reevaluated after three months of treatment. The International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were recorded at baseline and after three months. ### results Mean age was 63.3 ± 6.6 and 61.4 ± 7.5 years in groups 1 and 2, respectively (p = 0.245). There were no statistically significant differences between both groups. Also, baseline prostate specific antigen (PSA), prostate volume, creatinine, International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were similar in both groups. In addition, the total IPSS, IPSS-QoL, PVR, nocturia, and PSQS were significantly lower in Group 2 compared with Group 1 after treatment (p < 0.05). Qmax and AFR were higher significantly in Group 2 compared with Group 1 after treatment (p < 0.05). ### conclusions Cyclooxygenase (COX)-2 inhibitors in combination with an alpha blocker may decrease benign prostatic hyperplasia symptoms and increase sleep quality without serious side effects.


doxorubicin

etoposide

cisplatinum

Induction of drug resistance in human rhabdomyosarcoma cell lines is associated with increased maturation: possible explanation for differentiation in recurrences? In rhabdomyosarcoma (RMS) of childhood and adolescence very little is known about interactions of cytotoxic drugs and tumor cells. In recurrent RMS the tumor cells are often more mature than in the primary tumor. The biological properties of these cells are still a subject of controversy. We investigated two human ( RD2 and TE 671 ) cell lines by cultivating them with doxorubicin , cisplatinum , and etoposide . Degree of differentiation and proliferation rate were estimated morphologically and by means of immunohistochemistry and a monolayer proliferation assay. Both morphological and immunohistochemical maturation was measurable in most resistant cell lines. An increase in myosin expression was most marked in the etoposide- and doxorubicin-resistant RD cell lines. The proliferation rate was decreased in almost all resistant cell lines. Nevertheless, the resistant cell lines tolerated high-dose levels of cytotoxic drugs at a higher proliferation rate than parental cell lines cultivated under similar conditions. The maturation seen in some recurrent tumors of RMS can be simulated in vitro by cultivating cell lines with cytotoxic drugs at sublethal doses. Interestingly, the resistance-associated induced maturation was not accompanied by p170 expression. After comparing these in vitro results with the maturation seen in RMS specimens after chemotherapy, we conclude that chemotherapy-induced differentiation in vivo might be a morphological sign of chemoresistance.


simvastatin

ezetimibe

Retrospective study on antihyperlipidemic efficacy and safety of simvastatin , ezetimibe and their combination in Korean adults . Antihyperlipidemic agents such as 3-hydroxymethyglutaryl-coenzyme A reductase inhibitors and cholesterol transporter inhibitors are used in coronary heart disease. However, controversy remains over the pharmacologic effects and safety of these drugs, especially when used in combination therapies. This retrospective study evaluated the therapeutic effect and safety of simvastatin 20 mg and ezetimibe 10 mg combination therapy compared to simvastatin 20 mg or ezetimibe 10 mg monotherapy in Korean patients according to gender, age, baseline low-density lipoprotein cholesterol, and cardiovascular risk factors. We observed significant differences among patient subgroups. simvastatin and ezetimibe monotherapies and combination therapy reduced low-density lipoprotein cholesterol levels by 27.6%, 10.1%, and 36.8% (p < 0.001) and total cholesterol levels by 17.5%, 9.2%, and 25.3% (p < 0.001), respectively. Both monotherapy and combination therapy groups had similar incidences of all types of adverse events. However, one case of rhabdomyolysis was observed in the combination therapy group. These results suggest that, compared to monotherapy, combination therapy has an additive effect that is not influenced by risk factors. Despite the low incidence of adverse events, caution is required when using these drugs, especially in the context of musculoskeletal side effects.


dacarbazine

nimustine

vincristine

cisplatin

Combination hepatic arterial infusion therapy is effective for ocular melanoma metastasis to the liver. Regional treatments including chemotherapy have been applied to patients with malignant melanoma metastasis to the liver in clinical trials, but with limited efficacy. To improve efficacy, combination therapy may be beneficial. We had a case of multiple liver metastasis from right ocular malignant melanoma. The primary melanoma was surgically resected , and combination hepatic arterial infusion ( HAI ) therapy using dacarbazine , nimustine , vincristine ( DAV ) , and cisplatin was applied to the metastatic focus . After HAI, marked regression of the liver metastatic focus was observed. Unfortunately, the patient passed away due to involvement of thrombotic thrombocytopenic purpura 9 months after the initial consultation, however, aggravation of the liver metastatic focus was not observed. Combination HAI therapy may have a potent therapeutic effect on malignant melanoma metastasis to the liver, and our regimen using DAV and CDDP may be beneficial to the improvement of prognosis without serious side effects.


Ara-C

mitoxantrone

etoposide

[Comparison of low-dose cytosine arabinoside and aclarubicin in combination with granulocyte colony-stimulating factor to intermediate-dose cytosine arabinoside and mitoxantrone with or without etoposide in the treatment of relapsed acute myeloid leukemia]. We used a new chemotherapy regimen for the treatment of 18 consecutive patients with relapsed AML. The regimen consisted of low-dose cytosine arabinoside (Ara-C), low-dose aclarubicin and concurrent use of G-CSF (CAG regimen). Fifteen out of 18 patients (83%) achieved complete remission (CR). Median CR duration and median survival were 6 months and 15 months, respectively. These results were similar to those of previously reported salvage therapies for relapsed AML including intensive chemotherapy consisting of intermediate-dose Ara-C and sequential mitoxantrone with or without etoposide ( MC/MEC ) , which we previously adopted . Myelosuppression and non-hematological toxicities were apparently lower and less frequent compared to MC/MEC. The CAG regimen seems promising for the treatment of relapsed AML with its low toxicity contributing to a high quality of life for the patient.


cisplatin

CDDP

doxorubicin

DXR

etoposide

Expression of multidrug-resistance-associated protein (MRP) and chemosensitivity in human gastric cancer. Evidence has accumulated that, in addition to the MDR1 gene-coded P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP) also mediates the multidrug resistance (MDR) of various human tumors. In the case of gastric cancer, there is little or no involvement of P-glycoprotein, and the mechanisms of MDR remain to be understood. To search for a possible relationship between expression of MRP and sensitivity to anti-cancer agents in gastric cancer, 4 gastric cancer cell lines, 43 human gastric carcinomas and 17 adjacent normal gastric tissue samples were analyzed. Expression of MRP mRNA was evaluated using reverse transcription PCR (RT-PCR) and Southern hybridization. Sensitivity of the test samples to the anti-cancer drugs cisplatin ( CDDP ) , doxorubicin ( DXR ) and etoposide ( VP-16 ) was examined using the MTT¿3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl [2H]-tetrazolium bromide ¿ assay . Immunohistochemical staining with the use of the MRP antibody (MRPr1) was done to confirm the findings regarding the expression of mRNA levels. The MRP expression evaluated with RT-PCR and Southern hybridization as well as with immunohistochemical staining revealed that 23 of 43 gastric-cancer tissues (53.5%), 15 of 17 normal gastric tissues (88%) and 3 of 4 gastric-cancer cell lines (75%) were positive. The MTT assay showed that DXR was significantly more sensitive (p < 0.01) in gastric carcinoma tissues lacking MRP expression than in those with positive expression. The same tendency was seen with the other agents used. Of the cell lines, one which showed no MRP expression also had a higher sensitivity to CDDP, DXR and VP-16 than the other positive cases. These results show that MRP expression is involved in MDR of human gastric cancer and is inversely related to the chemosensitivity of tumor cells against some anticancer drugs.


cyclophosphamide

alvocidib

rituximab

Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia. Alvocidib has demonstrated efficacy in high-risk chronic lymphocytic leukemia (CLL) patients. In this phase I study , we combined cyclophosphamide , alvocidib and rituximab ( CAR ) in a schema designed to mitigate tumor lysis syndrome ( TLS ) seen previously with alvocidib . Nine nucleoside analog-naïve, high-risk patients received escalating doses of CAR therapy. Dose limiting toxicity was not experienced. No instances of TLS were observed. Patient responses included three complete remissions and four partial remissions. CAR was tolerable and active in high-risk CLL patients without TLS toxicity. With continued monitoring of toxicities, a phase Ib/II study of this combination as frontline therapy is warranted.


desmoteplase

tenecteplase

[Current and future aspects of intravenous thrombolysis for acute stroke]. Intravenous thrombolysis using alteplase was approved for clinical use for acute ischemic stroke treatment in Japan in 2005, on the basis of the results of a domestic clinical trial, Japan alteplase Clinical Trial. This therapeutic strategy has become the standard strategy during the following 8 years. However, this therapy still has room for improvement. One of the important drawbacks of intravenous thrombolysis is the limited therapeutic time window. On the basis of the results of the European Cooperative Acute Stroke Study III and the pooled analysis, the current time window is within 4.5 h of stroke onset. The window may be extended to 6 h or longer, probably by appropriate determination of the eligibility of a patient for receiving therapy by using penumbral imaging techniques, such as diffusion-weighted imaging (DWI)/perfusion-weighted imaging mismatch and DWI/magnetic resonance imaging mismatch. Newer-generation recombinant tissue-type plasminogen activators , such as desmoteplase and tenecteplase , will also help extend the time window . Patients with wake-up and unclear-onset strokes are generally ineligible for thrombolysis; therefore, the optimal therapeutic strategy for such patients should be established. Another important drawback is acute stroke therapy paralleling or following intravenous thrombolysis. Mechanical recanalization by endovascular therapy, antithrombotic therapy, neuroprotective therapy (e.g., using intravenous free radical scavenger), and sonothrombolysis are promising candidates for combined use with intravenous thrombolysis.


cyclophosphamide

doxorubicin

etoposide

Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma: an Eastern Cooperative Oncology Group trial (E3493). Preclinical and clinical evidence suggest a potential advantage for infusional therapy in lymphoma. Sixty-two analyzable patients with predominantly intermediate-grade non-Hodgkin lymphoma received cyclophosphamide ( 200 mg/m(2 ) per day ) , doxorubicin ( 12.5 mg/m(2 ) per day ) , and etoposide ( 60 mg/m(2 ) per day ) ( CDE ) by continuous intravenous infusion for 4 days ( 96 hours ) every 3 weeks for a maximum of 8 cycles . By the age-adjusted International Prognostic Index (IPI), 42% were at high risk and 58% were at high-intermediate risk. Complete response (CR) occurred in 30 (48%) patients (95% confidence interval [CI], 35%, 64%), and partial response occurred in 16 (26%) patients, yielding an overall response rate of 74% (95% CI, 62%, 84%). Failure-free survival (FFS) rates at 1 and 2 years were 55% (95% CI, 43%, 67%) and 50% (95% CI, 38%, 62%), respectively. When comparing the outcome for 62 patients receiving infusional CDE with historical data derived from 927 IPI-matched lymphoma patients using a Cox proportional hazards model, there was a nonsignificant trend favoring CDE in FFS (P =.12) and overall survival (P =.09). Severe or life-threatening toxicity included neutropenia (68%), anemia (57%), thrombocytopenia (44%), and infection (24%). Two patients (3%) died of treatment-related infectious complications. The primary end point of improving 1-year FFS from 55% to 70% was not achieved with infusional CDE given as initial therapy in patients with poor-risk intermediate-grade lymphoma. It is unlikely that infusional therapy as used in this study produces a 25% or greater relative improvement in FFS compared with standard therapy.


cytisine

mecamylamine

scopolamine

ketanserin

Fluorine-18-FPH for PET imaging of nicotinic acetylcholine receptors. Visualization of central nicotinic acetylcholine receptors (nAChRs) with modern PET or SPECT imaging techniques has been hampered by the lack of a radioligand with suitable in vivo binding characteristics (i.e., high target-to-nontarget ratios and kinetics appropriate for the half-life of the tracer and imaging modality used). This paper describes in vivo binding, kinetics and pharmacology of a highly potent 18F-labeled analog of epibatidine, (+/-)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), in the mouse brain with the view towards application of this tracer for PET imaging of nAChR in human brain. ### methods Fluorine-18-FPH was administered intravenously to mice, and time-activity curves were determined for several regions in the brain and other organs. Saturation and pharmacology of [18F]FPH binding was demonstrated in vivo by preinjecting unlabeled FPH or other drugs with known pharmacological action before [18F]FPH was injected. The effect of the drugs on [18F]FPH accumulation was evaluated. ### results [18F]FPH was rapidly incorporated into the mouse brain; peak activity (2.4% of the injected dose) was measured at 5 min after intravenous administration, followed by washout to 1.1% injected dose (ID) at 60 min. Highest concentrations of 18F occurred at 15 min in areas known to contain high densities of nAChR ¿e.g., thalamus [9.7% of injected dose per gram tissue (ID/g¿] and superior colliculus (8.3% ID/g)]. Accumulation of the 18F tracer in hippocampus, striatum, hypothalamus and cortical areas was intermediate (5.0, 5.6, 4.2 and 5.6% ID/g, respectively) and low in the cerebellum (2.8% ID/g). The distribution of [18F]FPH in the mouse brain matched that of other in vivo nAChR probes such as 3H-labeled epibatidine or norchloroepibatidine, [3H](-)-nicotine and [3H]cytisine and that of nAChR densities determined in postmortem autoradiographic studies in rodents. Preinjection of blocking doses of unlabeled epibatidine , (-)-nicotine , lobeline and cytisine significantly inhibited [18F]FPH binding in thalamus and superior colliculus , but not in cerebellum , whereas drugs that interact with binding sites other than acetylcholine recognition sites of nAChR ( e.g. , mecamylamine , scopolamine , N-methylspiperone and ketanserin ) had no effect on [18F]FPH accumulation in any of the brain regions examined . ### conclusion Fluorine-18-FPH labels nAChR in vivo in the mouse brain. Because of its high uptake into the brain and high ratios of specific-to-nonspecific binding, this radioligand appears to be ideally suited for PET imaging of nAChR in the mammalian brain.


carboplatin

etoposide

ifosfamide

Carboplatin, etoposide, and ifosfamide as second-line treatment for ovarian cancer. A total of 25 patients with epithelial ovarian cancer were treated with second-line carboplatin, etoposide, and ifosfamide (ICE) following failure of first-line cisplatin-based combination chemotherapy. The combination carboplatin 35 mg/m2 , etoposide 50 mg/m2 , and ifosfamide 1,200 mg/m2 was administered intravenously daily for 3 consecutive days . Response was seen in 13 patients (52%) with 7 complete responses (28%) and 6 partial responses (24%). Median duration of response was 9+ months (range: 4-17+ months). Response rate to second-line ICE relates directly to prior response to first-line cisplatin-based chemotherapy: 12 patients (67%) responded to second-line ICE who responded to first-line cisplatin-based chemotherapy, while only 1 patient (14%) responded who progressed on first-line cisplatin-based chemotherapy. Median survival was 18+ months (range: 2-31+ months). There were six episodes (4%) of grade 4 neutropenia, seven episodes (4%) of grade 4 thrombocytopenia and no grade 3 or 4 nonhematologic toxicity. ICE has moderate activity with minimal toxicity as second-line treatment of advanced epithelial ovarian cancer.


Aspirin

tamoxifen

Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells . tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.


cefotaxime

metronidazole

Antibacterial Prophylaxis in Emergency Surgery of Abdominal Infection. The results of antibiotic prophylaxis in 148 patients with destructive acute surgical sicknesses of abdominal cavity being urgently operated in the Republican hospital of Baku city from 2011 to 2016 were analyzed. Sixty-five patients were in the basic group which had got as preoperative antibiotic prophylaxis 120-hour course of amoxiclav (amoxicillin in combination with clavulanic acid). Eighty-three patients were in the control group who have performed a surgical intervention with pre-operative 120-hour antibiotic prophylaxis by Claforan ( cefotaxime ) combining with Metrogel ( metronidazole ) . it was showed that applying antibiotic prophylaxis using amoxiclav positively lowered the frequency of as postoperative purulent-septic complications as recurring operations to 8.1%.


CD DP

leucovorin

etoposide

doxorubicin

[Etoposide, doxorubicin, cisplatin and 5-FU (EAP-F) therapy of advanced gastric cancer--its antitumor effect and evaluation of quality of life]. Fourteen patients with advanced gastric cancer were treated with EAP-F therapy. The regimen was CD DP 40 mg/m2 day 1 and 6 , 5-FU 600 mg/m2 day 2 and 4 , leucovorin 20 mg/m2 day 2 and 4 , etoposide 60 mg/m2 day 3 and 5 , and doxorubicin 20 mg/m2 day 7 , with repetition every 28 days . Thirteen patients were evaluable; one patient was CR, four were PR, five were NC and three were PD. The response rate was 38.5% and median survival was 7 months. Hematologic toxicities were moderate to severe but tolerable, gastrointestinal toxicities were mild and renal toxicity was absent. Quality of life (QOL) of the patients was evaluated by means of symptom-free ratio (duration of symptom-free to survival time) and outpatient ratio (duration at home in relation to survival time). Patients with lymph node metastasis showed a higher symptom-free ratio and outpatient ratio than those with liver metastasis or peritoneal dissemination. All high-QOL patients were chemotherapy responders. In conclusion, EAP-F therapy is effective for advanced gastric cancer and its side effects are tolerable. CR or PR is necessary to achieve a high QOL.


bleomycin

etoposide

doxorubicin

cyclophosphamide

vincristine

procarbazine

prednisolone

Multicentre phase II study of the baseline BEACOPP regimen for patients with advanced-stage Hodgkin's lymphoma.  A German Hodgkin 's lymphoma ( HL ) study group designed the BEACOPP ( bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , prednisolone ) regimen . In the BEACOPP regimen, treatment intervals were shortened and the dose-intensity was increased compared with those in the ABVD regimen (doxorubicin, bleomycin, vinblastine and darcarbacine), resulting in a long-term disease-free survival rate of approximately 75-80%. In the present study, we evaluated the safety and efficacy of the BEACOPP regimen. Between April 2001 and February 2004, 20 patients with HL of stage IIB or higher who had received no previous treatment were enrolled. The patients were aged 17-69 years (median 22 years). The histologic types were mixed cellularity in four cases and nodular sclerosis in 16 cases. The stages were stage IIB in four cases, stage III in 12 cases, and stage IV in four cases. Nineteen (95%) of the 20 patients achieved complete remission. The 3-year survival rate was 100% and the 3-year progression-free survival rate was 89.7%. Adverse drug reactions were grade 4 neutropenia in 12 patients, grade 3-4 thrombocytopenia in seven patients, and grade 3 or higher non-hematologic toxicities in two patients (stomatitis in one patient and ALT/AST elevation in one patient). The BEACOPP regimen for advanced-stage HL showed an excellent complete remission rate and high efficacy even in stage III/IV patients. However, a long-term risk of the BEACOPP regimen is the development of secondary leukemia or myelodysplastic syndrome. Therefore, long-term follow-up of these patients, including monitoring for toxicities, is necessary.


doxorubicin

cyclophosphamide

doxorubicin

cyclophosphamide

Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A --> C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC). ### Patients And Methods High-risk node-negative or low-risk node-positive breast cancer patients received AC given : ( arm I ) concurrently ( AC ) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously ( IV ) every 3 weeks for six cycles ; or ( arm II ) in sequence ( A C ) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles . Total dose and duration were identical, but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy. ### results Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor-positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A --> C. Grade 4 hematologic toxicity was greater on A --> C, but nonhematological grade 4 was similar. ### conclusion The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.


cyclophosphamide

doxorubicin

vincristine

cisplatin

etoposide

Dose-intensive weekly alternating chemotherapy for patients with small cell lung cancer: randomized trial, can it improve survival of patients with good prognostic factors? We conducted a randomized trial of dose-intensive weekly alternating chemotherapy (CAV/PE-W) and standard alternating chemotherapy (CAV/PE) in small cell lung cancer (SCLC) patients with good prognostic factors. A total of 76 patients with SCLC was randomized. The CAV/PE-W consisted of 4 alternating cycles of cyclophosphamide : 500 mg/m2 , doxorubicin : 30 mg/m2 , and vincristine : 1 mg/m2 ( day 1 ) and cisplatin : 50 mg/m2 ( day 8) and etoposide : 75 mg/m2 ( days 8 and 9 ) . The CAV/PE consisted of 2 alternating cycles of cyclophosphamide: 800 mg/m2, doxorubicin: 50 mg/m2, and vincristine: 1.4 mg/m2 (day 1), cisplatin: 100 mg/m2 (day 22) and etoposide: 100 mg/m2 (days 22, 23 and 24). Eligibility criteria were no prior therapy, no active concomitant malignancy, ECOG PS of 0 or 1, age < or =75, adequate hematologic functions and no brain metastasis. The complete response (CR) rate for CAV/PE-W (14/38, 36.8%) was significantly higher than that for CAV/PE (6/38, 15.8%, chi2; p=0. 032). However, the response rate in patients on CAV/PE-W (36/38, 94. 7%) was not significantly higher than the rate for CAV/PE (31/38, 81. 6%, chi2; p=0.076). Progression-free survival for patients on CAV/PE-W was significantly longer than that of patients on CAV/PE (41.4 weeks vs. 21.3 weeks, log-rank; p=0.0007, generalized Wilcoxon; p=0.0034) as was overall median survival (67.0 weeks vs. 51.2 weeks, log-rank; p=0.028). Actual dose-intensity of CAV/PE-W was 1.74 times that of CAV/PE. Hematological toxicities were equally frequent and G-CSF contributes to treatment efficacy by allowing administration of dose-intensive chemotherapy. The CAV/PE-W achieved a higher CR rate and longer survival, than the CAV/PE.


Cyclophosphamide

methotrexate

folinic acid

Cyclophosphamide , methotrexate , 5-fluorouracil , and folinic acid ( CMFF ) as first line chemotherapy for treatment of advanced breast cancer . In order to evaluate the maximum tolerable dose of a combination chemotherapy consisting of cyclophosphamide, methotrexate, 5-fluorouracil, and folinate (CMFF), 30 female patients with histopathologically confirmed, previously untreated advanced breast cancer were entered into this pilot study. Chemotherapy consisted of fixed doses for methotrexate (40 mg/m2 i.v. on day 1), 5-fluorouracil (500 mg/m2 i.v. on day 2 to 4) and folinic acid (2 x 200 mg/m2 i.v., 0 + 2 h on day 2 to 4). The dose of cyclophosphamide was escalated stepwise, starting with 200 mg/m2 i.v. on day 2 to 4, to 240 mg/m2, 290 mg/m2, 360 mg/m2 and 400 mg/m2, respectively, for each subsequent five patients. Treatment was repeated every four weeks. A total of 92 treatment cycles was given. Myelosuppression was the dose-limiting toxicity: leukopenia WHO grade III or IV was observed after a total of 28 cycles and anemia of equal intensity after 1 cycle. No thrombocytopenia WHO grade III or IV was recorded. Myelotoxicity increased with higher doses of cyclophosphamide. Among non-hematologic toxicities, alopecia was reported in two-thirds of the patients. Nausea and vomiting was noted in 25% of treatment cycles, but in one cycle only WHO grade III was recorded. No other toxicities exceeding WHO grade II occurred.(ABSTRACT TRUNCATED AT 250 WORDS)


rosuvastatin

rosuvastatin

fenofibrate

High doses of rosuvastatin are superior to low doses of rosuvastatin plus fenofibrate or n-3 fatty acids in mixed dyslipidemia . The aim of the study was to compare the efficacy of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega-3 fatty acids with regard to the lipid profile in patients with mixed hyperlipidemia. The primary endpoint was changes in non-high density lipoprotein-cholesterol (non-HDL-C) levels. Study participants were randomly allocated to receive rosuvastatin 40 mg (n = 30, R group), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, RF group) or rosuvastatin 10 mg plus n-3 fatty acids 2 g (n = 30, RN group). Non-HDL-C levels were reduced in all groups: in R group by 54%, in RF group by 42% and in RN group by 42%. Significant reductions in total cholesterol (TC), low density lipoprotein (LDL)-C and triglyceride levels were observed in all groups. The reductions in total and LDL-C were greatest in the R group while a more pronounced reduction of triglycerides in the RF group compared with that in the R and the RN group was observed. HDL-C levels were significantly increased only in the RF group. In conclusion, high doses of rosuvastatin and small doses of rosuvastatin plus either fenofibrate or n-3 fatty acids exhibit favorable effects on both LDL-C and non-HDL-C levels. However, rosuvastatin monotherapy more potently reduces these parameters. The combination of rosuvastatin plus fenofibrate leads to a greater decrease in triglyceride levels and a greater increase in HDL-C levels compared with the other two treatments. While awaiting the results of ongoing trials high doses of rosuvastatin may represent the treatment of choice in individuals with mixed dyslipidemia.


bupivacaine

bupivacaine

triamcinolone

bupivacaine

triamcinolone

Effects of stellate ganglion block on breast cancer-related lymphedema: comparison of various injectates. To determine the effects of SGB in BCRL patients and the efficacy of corticosteroids in SGB. ### Study Design A double-blinded, randomized, controlled trial. ### setting A single academic hospital, outpatient setting. ### methods In total, 32 patients with BCRL were recruited. Patients were divided randomly into 3 groups ( Group A : 0.5 % bupivacaine 5 mL , n = 12 ; Group B : 0.5 % bupivacaine 4.5 mL + 20 mg of triamcinolone 0.5 mL , n = 10 ; and Group C : 0.5 % bupivacaine 4 mL + 40 mg of triamcinolone 1 mL , n = 10 ) . All patients received 3 consecutive SGBs, every 2 weeks. The primary outcomes were changes in forearm and upper arm circumference. Circumference was measured at baseline, 2 weeks (before the second injection), 4 weeks (before the third injection), and 8 weeks (one month follow-up after 3 consecutive SGBs). Moreover, subjective data were collected using EORTC C-30 at baseline and 8 weeks. ### results After 3 consecutive SGBs, forearm and upper arm circumferences were decreased significantly from baseline in all groups (P < 0.05/3). The upper arm circumference of group C was reduced significantly more than that of group A (P < 0.05/3). The subjective data by EORTC-C30 at baseline and one month after 3 consecutive SGBs revealed no statistically significant difference. ### limitations Relatively few patients were enrolled. We did not compare SGB with any other BCRL treatment, such as complex decongestive therapy. ### conclusions This study suggests that SGB may be an effective treatment for BCRL. Furthermore, it appears that corticosteroids could have an additive effect in SGB.


Irinotecan

etoposide

irinotecan

etoposide

Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma. irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy, we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity. Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil, as single agents, were 30 and <10%, respectively. etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3] i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined using the ( d x 5)2 i.v . schedule for both drugs , in which irinotecan was given 2 h before or 2 h after the administration of etoposide . Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia. The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.


sofosbuvir

pegylated-interferon

ribavirin

Combination of sofosbuvir , pegylated-interferon and ribavirin for treatment of hepatitis C virus genotype 1 infection : a systematic review and meta-analysis . Hepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis. ### methods In this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis. ### results After screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ ### conclusions Combination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.


Cyclosporin

Azathioprine

[Predictive variables of early mortality after orthotopic heart transplant in adults]. The purpose of the study was to analyze some variables of donors, recipients and surgical procedures in order to discover factors that could predict mortality during the early stage (< 30 days) of orthotopic heart transplants. ### Material And Method 125 consecutive orthotopic heart transplants in adults were analyzed. The average age was 51 +/- 11 (range: 12-67), 109 (87%) were men, 16 were women (13%). Two groups were compared: 15 patients who died within 30 days after heart transplant and 110 who survived during that period. Immunosuppressive protocol : preoperative : Cyclosporin + Azathioprine . Intraoperative: methylprednisolone Postoperative: methylprednisolone (first 24 h), antilymphocyte monoclonal antibodies (7-10 days after heart transplant) + cyclosporin + azathioprine + Corticoids. The following parameters of the recipient were analyzed: sex, age, weight, size, thoracic perimeter, pretransplant cardiopathy, previous thoracic operations, functional stage or need for catecholamines during the days prior to the transplant, pulmonary artery pressure and resistance, history of systemic arterial hypertension, elevation of creatinine, blood type, urgent transplant indication, receptor/donor weight relationship. The following parameters of donors and operation were analyzed: sex, age, weight, thoracic perimeter, period in intensive care unit, dose of dopamine and dobutamine, blood type, origin of the organ, cause of death, ischaemia time, cardiopulmonary by-pass time and cardioplegia type. ### results The rate of early mortality was 12%. The univariate analysis showed differences in: prior cardiovascular surgery, receptor blood type, need for urgent transplantation, pulmonary artery resistance > 2.5 Wood Units, cardiopulmonary by-pass time, weight relationship between receptor and donor. The death cause of the donor proved significant. On multivariate analysis, the following parameters independently predicted early mortality: history of operation with extracorporeal circulation, high pulmonary artery resistance, urgent transplant, receptor/donor weight relation and time of extracorporeal circulation. ### conclusions We believe that the results of our experience can help to stratify the risk in the orthotopic heart transplant recipient and even to contraindicate the procedure in some cases showing an accumulation of poor prognostic factors in borderline recipients.


sunitinib

interferon alfa

Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma . A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. ### Patients And Methods Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. ### results Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%). ### conclusion sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.


doxorubicin

etoposide

Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: a report from the National Wilms Tumor Study Group. This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. ### Patients And Methods The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. ### results Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin ( 6 ) or etoposide ( 1 ) , and six were treated with infradiaphragmatic irradiation . The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2-4 yrs). One patient had the translocation t(9:11)(p22;q23); WT1 status was not noted for any of the seven patients. ### conclusions The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer.


aspirin

warfarin

clopidogrel

clopidogrel

aspirin

Systematic review with meta-analysis: the risk of gastrointestinal haemorrhage post-polypectomy in patients receiving anti-platelet, anti-coagulant and/or thienopyridine medications. For patients undergoing colonoscopy with polypectomy, current guidelines recommend temporary cessation of blood-thinning medications. The data regarding periprocedural management of these medications are sparse. ### aim To perform a systematic review and meta-analysis to determine the risk of post-polypectomy bleeding (PPB) in patients taking anti-platelet, anti-coagulant and/or thienopyridine medications. ### methods We searched Pubmed, Scopus, Web of Science, Biosis and Proceedings First from 1970 to 2015. PPB was defined as overt haemorrhage or drop in haemoglobin of at least 2 g/dL. ### results Of 1490 articles identified , we included 3 papers and 1 abstract with patients on aspirin and/or NSAIDs , 1 paper on warfarin , 2 abstracts on clopidogrel , and 2 papers on clopidogrel plus aspirin and/or NSAIDs . While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR = 1.1, 95% CI 0.7-1.9, P = 0.7), the risk of delayed PPB was increased (OR = 1.7, 95% CI 1.0-2.4, P = 0.0009, I(2)  = 60%) but rendered non-significant with elimination of a small study. There was an elevated risk of delayed PPB on clopidogrel (OR = 9.7, 95% CI 3.1-30.8, P = 0.0, I(2)  = 0). There was an increased risk of delayed PPB in patients on clopidogrel + aspirin and/or NSAIDs (OR = 3.4, 95% CI 1.3-8.8, P = 0.01, I(2)  = 0). Based on a single study on warfarin, the PPB rate was elevated. There were no data regarding PPB and usage of the newer anti-coagulant agents. ### conclusions Usage of aspirin or NSAIDs does not increase risk of post-polypectomy bleeding. clopidogrel and warfarin should be discontinued in the periprocedural period to prevent the occurrence of post-polypectomy bleeding.