Disease relevance of Gemzar

• Anal pruritus after cancer chemotherapy with gemcitabine [1].
• We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC [2].
• CONCLUSIONS: Gemcitabine is a well-tolerated new drug with activity in platinum-resistant ovarian cancer patients [3].
• Delayed anemia and thrombocytopenia after treatment with gemcitabine [4].
• Membranoproliferative glomerulonephritis following gemcitabine and vinorelbine chemotherapy for peritoneal mesothelioma [5].
• Silencing of p65/relA induced apoptosis and increased gemcitabine killing of all gemcitabine-sensitive pancreatic cancer cells [6].
• Concentration-based exposure metrics for gemcitabine and its metabolites were no better than gemcitabine amount in predicting tumor shrinkage in primary lung cancer lesions [7].
• The DeltaE1B19K-deleted mutants synergized with gemcitabine to selectively kill cultured pancreatic cancer cells and xenografts in vivo with no effect in normal cells [8].
• An enhanced activity of carboplatin in platinum-resistant ovarian cancer may be due to synergy with gemcitabine through inhibition of repair of DNA cross-links [9].

Psychiatry related information on Gemzar

• When a single dose of QLT0254 and chemotherapy agent gemcitabine was administered, there was a significant 5.4-fold increase in acute apoptosis in the combination therapy group compared with vehicle controls (P = 0.002) [10].
• At a gemcitabine dose of 800 mg/m(2), 1/6 patients had a dose limiting toxicity (DLT) (grade 3 blurred vision and memory loss) [11].

High impact information on Gemzar

• We also used the two-electrode, voltage-clamp technique to investigate the electrophysiology of hCNT1-mediated gemcitabine transport [12].
• Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters [12].
• Gemcitabine had a limited ability to cross the lipid bilayer of oocyte membranes by simple diffusion [12].
• Variation in the tumor and tissue distribution of plasma membrane nucleoside transporter proteins may contribute to the solid tumor activities and schedule-dependent toxic effects of gemcitabine [12].
• Gemcitabine-induced hemolytic uremic syndrome: a case report [13].

Chemical compound and disease context of Gemzar

• We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial [14].
• No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide [15].
• Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer [16].
• CS-682 was found to exhibit superior efficacy by delaying the onset and inhibiting the growth of liver metastasis compared with gemcitabine, 5-FU, and control [17].
• PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma [18].
• Overall, our results suggest that curcumin potentiates the antitumor effects of gemcitabine in pancreatic cancer by suppressing proliferation, angiogenesis, NF-kappaB, and NF-kappaB-regulated gene products [19].

Biological context of Gemzar

• Influxes of gemcitabine mediated by hCNT1, hENT1, and hENT2 were saturable and conformed to Michaelis-Menten kinetics with apparent K(m) values of 24, 160, and 740 microM, respectively [12].
• Inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine, whereas inhibition of miR-141 decreased cell growth [20].
• Here we show that nicotine inhibits apoptosis induced by the drugs gemcitabine, cisplatin, and taxol, which are used to treat NSCLCs [21].
• To determine the factors that limit the phosphorylation efficiency of the prodrug, we solved the crystal structure of dCK to a resolution of 1.6 A in complex with its physiological substrate deoxycytidine and with the prodrugs AraC and gemcitabine [22].
• Hematopoietic stem cell gene transfer of the drug-resistance gene cytidine deaminase (CDD) protecting cells from the cytotoxic cytidine analogs cytarabine and gemcitabine was investigated in a murine transplant model [23].

Anatomical context of Gemzar

• The efficiency of gemcitabine uptake varied markedly among the cell lines with single NTs: es approximately = cit > ei > cib >>> cif [24].
• In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms [25].
• Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study [26].
• Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group [27].
• PATIENTS AND METHODS: Fifty-one chemotherapy-naive patients with NSCLC were treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel 100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150 microg/m2, subcutaneously) support from day 9 to day 15 [28].

Associations of Gemzar with other chemical compounds

• Here, we present three x-ray structures of eukaryotic Rnr1 from Saccharomyces cerevisiae: one bound to gemcitabine diphosphate (GemdP), the active metabolite of the mechanism-based chemotherapeutic agent gemcitabine; one with an Rnr2-derived peptide, and one with an Rnr4-derived peptide [29].
• Hits identified in drug enhancer screens of cisplatin, gemcitabine, and paclitaxel were largely unique to the drug being tested and could be linked to the drug's mechanism of action [30].
• Median progression-free survival for the gemcitabine/5-FU group was 28.7 weeks versus 8 weeks for a similar cohort of patients treated on previous phase II studies at the University of Chicago (P =.008) [31].
• Paclitaxel, however, dose-dependently increased the C(max) of gemcitabine triphosphate (dFdCTP), the active metabolite of gemcitabine, from 55 +/- 10 to 106 +/- 16 pmol/10(6) cells.( )No significant difference in the AUC of dFdCTP was observed [32].
• The CCRF-CEM leukemia cell line was highly sensitive to the antiproliferative effects of troxacitabine, gemcitabine, and cytarabine with inhibition of proliferation by 50% observed at 160, 20, and 10 nM, respectively, whereas a deoxycytidine kinase (dCK)-deficient variant (CEM/dCK(-)) was resistant to all three drugs [33].
• Treatment of BxPC-3 cells with gemcitabine before erlotinib enhanced gemcitabine-mediated cytotoxicity without abrogating radiosensitization [34].
• Although dFdC is not a chain terminator, the incorporated dFdCMP decreased the incorporation efficiency of the next 2 correct nucleotides by 214- and 7-fold, respectively [35].
• Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no activity in patients with very advanced ACC [36].
• Feasibility of combining gemcitabine with an yttrium-90-labeled anti-CEA antibody is shown with preliminary evidence of clinical response [37].

Gene context of Gemzar

• The results from this study indicate that the level of RRM1 may affect gemcitabine response [38].
• Simultaneous inhibition of EGFR, VEGFR, and platelet-derived growth factor receptor signaling combined with gemcitabine produces therapy of human pancreatic carcinoma and prolongs survival in an orthotopic nude mouse model [39].
• No significant change in the expression of RRM2 was observed in either cell line, although both gemcitabine-resistant cell lines had an approximate 3-fold increase in p53R2 protein [38].
• The effects of modulating CEACAM6 expression on gemcitabine-induced cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay, flow cytometric apoptosis quantification, caspase profiling, and Western analysis of cytoplasmic cytochrome c release [40].
• Here we show that E2F1 in combination with the most clinically efficient drug, gemcitabine, resulted in a strong induction of apoptosis independent of functional p53, whereas the effect of either therapy alone varied between different cell lines [41].
• These observations indicate that down-regulation of Plk-1 expression by RNAi enhances gemcitabine sensitivity and increases gemcitabine cytotoxicity in pancreatic tumour cells [42].
• Our findings suggest that HMGA1 promotes chemoresistance to gemcitabine through an Akt-dependent mechanism [43].
• Pancreatic adenocarcinoma patients with a high expression of hENT1 and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation [44].

Analytical, diagnostic and therapeutic context of Gemzar

• All responders started treatment with gemcitabine within 6 months of prior treatment, and seven of the eight responders were resistant to first-line platinum-containing combination chemotherapy [3].
• Gemcitabine (2',2'-difluorodeoxycytidine) has shown a broad spectrum of antineoplastic activity in tumor cell cultures in vitro and in animal tumor models [3].
• METHODS: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)) [2].
• CONCLUSION: Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated [45].
• RESULTS: The study was closed to accrual after the second interim analysis on the basis of the recommendation of the National Cancer Institute of Canada Clinical Trials Group Data Safety Monitoring Committee. There were 277 patients enrolled onto the study, 138 in the BAY 12-9566 arm and 139 in the gemcitabine arm [46].

References