Cellular pharmacology of gemcitabine

Hertel, 1988, Synthesis of 2-deoxy-2′,2′difluoro-D-ribose and 2-deoxy-2′,2′difluoro-D-ribofuranosyl nucleosides, J Org Chem, 53, 2406, 10.1021/jo00246a002

Burris, 1997, Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial, J Clin Oncol, 15, 2403, 10.1200/JCO.1997.15.6.2403

Sandler, 2000, Phase III trial of gemcitabine plus cisplatin vs. cisplatin alone in patients with locally advanced or metastatic non-small cell lung cancer, J Clin Oncol, 18, 122, 10.1200/JCO.2000.18.1.122

von der Maase, 2000, Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study, J Clin Oncol, 18, 3068, 10.1200/JCO.2000.18.17.3068

Albain, 2004, Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall survival, Proc. ASCO 22, No 14S (July 15 Supplement), 510

Heinemann, 1988, Comparison of the cellular pharmacokinetics and toxicity of 2′,2′-difluorodeoxycytidine and 1-beta-D-arabinofuranosylcytosine, Cancer Res, 48, 4024

Hertel, 1990, Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine), Cancer Res, 50, 4417

Gandhi, 1990, Modulatory activity of 2′,2′-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides, Cancer Res, 50, 3675

Huang, 1991, Action of 2′,2′-difluorodeoxycytidine on DNA synthesis, Cancer Res, 51, 6110

Schy, 1993, Effect of a template-located 2′,2′-difluorodeoxycytidine on the kinetics and fidelity of base insertion by Klenow (3′ → 5′exonuclease-) fragment, Cancer Res, 53, 4582

Gandhi, 1996, Excision of 2′,2′-difluorodeoxycytidine (gemcitabine) monophosphate residues from DNA, Cancer Res, 56, 4453

Ruiz van Haperen, 1993, 2′,2′-Difluorodeoxycytidine (gemcitabine) incorporation into RNA and DNA of tumour cell lines, Biochem Pharmacol, 46, 762, 10.1016/0006-2952(93)90566-F

Heinemann, 1990, Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2′,2′-difluorodeoxycytidine, Mol Pharmacol, 38, 567

Baker, 1991, 2′-Deoxy-2′-methylenecytidine and 2′-deoxy-2′,2′-difluorocytidine 5′-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase, J Med Chem, 34, 1879, 10.1021/jm00110a019

Ruiz van Haperen, 1994, Schedule dependence of sensitivity to 2′,2′-difluorodeoxycytidine (Gemcitabine) in relation to accumulation and retention of its triphosphate in solid tumour cell lines and solid tumours, Biochem Pharmacol, 48, 1327, 10.1016/0006-2952(94)90554-1

Heinemann, 1995, Gemcitabine: a modulator of intracellular nucleotide and deoxynucleotide metabolism, Semin Oncol, 22, 11

Heinemann, 1992, Cellular elimination of 2′,2′-difluorodeoxycytidine 5′-triphosphate: a mechanism of self-potentiation, Cancer Res, 52, 533

Pourquier, 2002, Gemcitabine (2′,2′-difluoro-2′-deoxycytidine), an antimetabolite that poisons topoisomerase I, Clin Cancer Res, 8, 2499

Bergman, 2002, Determinants of resistance to 2′,2′-difluorodeoxycytidine (gemcitabine), Drug Resist Update, 5, 19, 10.1016/S1368-7646(02)00002-X

Spratlin, 2004, The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma, Clin Cancer Res, 10, 6956, 10.1158/1078-0432.CCR-04-0224

Bengala, 2005, Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma, Br J Cancer., 93, 35, 10.1038/sj.bjc.6602673

Rosell, 2004, Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients, Clin Cancer Res, 10, 1318, 10.1158/1078-0432.CCR-03-0156

Peters, 2000, Basis for effective combination cancer chemotherapy with antimetabolites, Pharmacol Ther, 87, 227, 10.1016/S0163-7258(00)00086-3

Plunkett, 1995, Gemcitabine: metabolism, mechanisms of action, and self-potentiation, Semin Oncol, 22, 3

Plunkett, 1996, Gemcitabine: preclinical pharmacology and mechanisms of action, Semin Oncol, 23, 3

Mackey, 1998, Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines, Cancer Res, 58, 4349

Belt, 1993, Nucleoside transport in normal and neoplastic cells, Adv enzyme Regul, 33, 235, 10.1016/0065-2571(93)90021-5

Griffith, 1996, Nucleoside and nucleobase transport systems of mammalian cells, Biochem Biophys Acta, 1286, 153

Ritzel, 2001, Mol Membr Biol, 18, 65, 10.1080/09687680010026313

Lostao, 2000, Electrogenic uptake of nucleosides and nucleoside-derived drugs by the human nucleoside transporter 1 (hCNT1) expressed in Xenopus laevis oocytes, FEBS Lett, 481, 137, 10.1016/S0014-5793(00)01983-9

Gati, 1997, Sensitivity of acute leukemia cells to cytarabine is a correlate of cellular es nucleoside transporter site content measured by flow cytometry with SAENTA-fluorescein, Blood, 90, 346, 10.1182/blood.V90.1.346

Galmarini, 2002, Potential mechanisms of resistance to cytarabine in AML patients, Leuk Res, 26, 621, 10.1016/S0145-2126(01)00184-9

Achiwa, 2004, Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer, Cancer Sci, 95, 753, 10.1111/j.1349-7006.2004.tb03257.x

Jansen, 1995, The influence of BIBW22BS, a dipyridamole derivative, on the antiproliferative effects of 5-fluorouracil, methotrexate and gemcitabine in vitro and in human tumour xenografts, Eur J Cancer, 31, 2313, 10.1016/0959-8049(95)00440-8

Bouffard, 1993, Kinetic studies on 2′,2′-difluorodeoxycytidine (Gemcitabine) with purified human deoxycytidine kinase and cytidine deaminase, Biochem Pharmacol, 45, 1857, 10.1016/0006-2952(93)90444-2

Wang, 1999, Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates, FEBS Lett, 443, 170, 10.1016/S0014-5793(98)01711-6

Kroep, 2002, Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity, Mol Cancer Ther, 1, 371

Abbruzzese, 1991, A phase I clinical, plasma, and cellular pharmacology study of gemcitabine, J Clin Oncol, 9, 491, 10.1200/JCO.1991.9.3.491

Neff, 1996, Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine, Exp Haematol, 24, 1340

Bergman, 1998, Increased sensitivity to gemcitabine of P-gP and MRP overexpressing human non-small cell lung cancer cell lines, Adv Exp Med Biol, 431, 591, 10.1007/978-1-4615-5381-6_114

Ruiz van Haperen, 1993, Deoxycytidine kinase and deoxycytidine deaminase activities in human tumour xenografts, Eur J Cancer, 29A, 2132, 10.1016/0959-8049(93)90048-K

Ruiz van Haperen, 1996, Regulation of phosphorylation of deoxycytidine and 2′,2′-difluorodeoxycytidine (gemcitabine); effects of cytidine 5′-triphosphate and uridine 5′-triphosphate in relation to chemosensitivity for 2′,2′-difluorodeoxycytidine, Biochem Pharmacol, 51, 911, 10.1016/0006-2952(95)02402-6

Oka, 1994, Molecular cloning of human cytosolic purine 5′-nucleotidase, Biochem Biophys Res Commun, 205, 917, 10.1006/bbrc.1994.2752

Hunsucker, 2001, Human cytosolic 5′-nucleotidase. Characterization and role in nucleotide analog resistance, J Biol Chem, 276, 10498, 10.1074/jbc.M011218200

Dumontet, 1999, Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562, Br J Haematol, 106, 78, 10.1046/j.1365-2141.1999.01509.x

Grunewald, 1990, Pharmacologically directed design of the dose rate and schedule of 2′,2′-difluorodeoxycytidine (Gemcitabine) administration in leukemia, Cancer Res, 50, 6823

Grunewald, 1991, Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine, Cancer Chemother Pharmacol, 27, 258, 10.1007/BF00685109

Rockwell, 1992, Effect of 2′,2′-difluorodeoxycytidine on the viability and radiosensitivity of EMT6 cells in vitro, Oncol Res, 4, 151

Iwasaki, 1997, Differential incorporation of ara-C, gemcitabine, and fludarabine into replicating and repairing DNA in proliferating human leukemia cells, Blood, 90, 270, 10.1182/blood.V90.1.270

Ross, 1994, Molecular effects of 2′,2′-difluorodeoxycytidine (Gemcitabine) on DNA replication in intact HL-60 cells, Biochem Pharmacol, 48, 1619, 10.1016/0006-2952(94)90207-0

Huang, 1995, Induction of apoptosis by gemcitabine, Semin Oncol, 22, 19

Kroep, 2000, Sequence dependent effect of paclitaxel on gemcitabine metabolism in relation to cell cycle and cytotoxicity in non-small-cell lung cancer cell lines, Br J Cancer, 83, 1069, 10.1054/bjoc.2000.1399

Goan, 1999, Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line, Cancer Res, 59, 4204

Davidson, 2004, An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines, Cancer Res, 64, 3761, 10.1158/0008-5472.CAN-03-3363

Bergman, 2005, In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant, Cancer Res, 65, 9510, 10.1158/0008-5472.CAN-05-0989

Ruiz Van Haperen, 1995, Gemcitabine inhibits thymidylate synthase (TS) activity in solid tumor cell lines, Proc Am Assoc Cancer Res, 36, 354

Gmeiner, 2003, Structural basis for topoisomerase I inhibition by nucleoside analogs, Nucleos Nucleot Nucl, 22, 653, 10.1081/NCN-120022604

Tolis, 1999, Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines, Eur J Cancer, 35, 796, 10.1016/S0959-8049(98)00425-0

Shi, 2002, Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes, Oncology, 62, 354, 10.1159/000065068

Ferreira, 2000, Chemotherapy triggers apoptosis in a caspase-8-dependent and mitochondria-controlled manner in the non-small cell lung cancer cell line NCI-H460, Cancer Res, 60, 7133

Chandler, 2004, Caspase-3 drives apoptosis in pancreatic cancer cells after treatment with gemcitabine, J Gastrointest Surg, 8, 1072, 10.1016/j.gassur.2004.09.054

Fukunaga, 2004, Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway, Pharmacogenomics J, 4, 307, 10.1038/sj.tpj.6500259