• 1
    Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004; 363: 104957.
  • 2
    Burris HA,III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 240313.
  • 3
    Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23: 350916.
  • 4
    Bergman AM, Pinedo HM, Peters GJ. Determinants of resistance to 2′,2′-difluorodeoxycytidine (gemcitabine). Drug Resist Updat 2002; 5: 1933.
  • 5
    Galmarini CM, Clarke ML, Falette N, Puisieux A, Mackey JR, Dumontet C. Expression of a non-functional p53 affects the sensitivity of cancer cells to gemcitabine. Int J Cancer 2002; 97: 43945.
  • 6
    Shi X, Liu S, Kleeff J, Friess H, Buchler MW. Acquired resistance of pancreatic cancer cells towards 5-FU and gemcitabine is associated with altered expression of apoptosis-regulating genes. Oncology 2002; 62: 35462.
  • 7
    Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. Inhibition of SRC tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells. Clin Cancer Res 2004; 10: 230718.
  • 8
    Duxbury MS, Ito H, Benoit E, Zinner MJ, Ashley SW, Whang EE. RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity. Biochem Biophys Res Commun 2003; 311: 78692.
  • 9
    Akada M, Crnogorac-Jurcevic T, Lattimore S, Mahon P, Lopes R, Sunamura M, Matsuno S, Lemoine NR. Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer. Clin Cancer Res 2005; 11: 3094101.
  • 10
    Mackey JR, Mani RS, Selner M, Mowles D, Young JD, Belt JA, Crawford CR, Cass CE. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res 1998; 58: 434957.
  • 11
    Rauchwerger DR, Firby PS, Hedley DW, Moore MJ. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res 2000; 60: 60759.
  • 12
    Davidson JD, Ma L, Flagella M, Geeganage S, Gelbert LM, Slapak CA. 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 2004; 64: 37616.
  • 13
    Bergman AM, Eijk PP, Ruiz van Haperen VW, Smid K, Veerman G, Hubeek I, van den Ijssel P, Ylstra B, Peters GJ. In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant. Cancer Res 2005; 65: 951016.
  • 14
    Dumontet C, Bauchu EC, Fabianowska K, Lepoivre M, Wyczechowska D, Bodin F, Rolland MO. Common resistance mechanisms to nucleoside analogues in variants of the human erythroleukemic line K562. Adv Exp Med Biol 1999; 457: 5717.
  • 15
    Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene 2004; 23: 153948.
  • 16
    Galmarini CM, Clarke ML, Jordheim L, Santos CL, Cros E, Mackey JR, Dumontet C. Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene. BMC Pharmacol 2004; 4: 8.
  • 17
    Eliopoulos N, Cournoyer D, Momparler RL. Drug resistance to 5-aza-2′-deoxycytidine, 2′,2′-difluorodeoxycytidine, and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into murine cells. Cancer Chemother Pharmacol 1998; 42: 3738.
  • 18
    Hsu SI, Lothstein L, Horwitz SB. Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes. J Biol Chem 1989; 264: 1205362.
  • 19
    Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992; 258: 16504.
  • 20
    Gatti L, Zunino F. Overview of tumor cell chemoresistance mechanisms. Methods Mol Med 2005; 111: 12748.
  • 21
    Maehara S, Tanaka S, Shimada M, Shirabe K, Saito Y, Takahashi K, Maehara Y. Selenoprotein P, as a predictor for evaluating gemcitabine resistance in human pancreatic cancer cells. Int J Cancer 2004; 112: 1849.
  • 22
    Goan YG, Zhou B, Hu E, Mi S, Yen Y. Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line. Cancer Res 1999; 59: 42047.
  • 23
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 5563.
  • 24
    Braakhuis BJ, Ruiz van Haperen VW, Boven E, Veerman G, Peters GJ. Schedule-dependent antitumor effect of gemcitabine in in vivo model system. Semin Oncol 1995; 22: 426.
  • 25
    Tsujie M, Nakamori S, Okami J, Hayashi N, Hiraoka N, Nagano H, Dono K, Umeshita K, Sakon M, Monden M. Thiazolidinediones inhibit growth of gastrointestinal, biliary, and pancreatic adenocarcinoma cells through activation of the peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha pathway. Exp Cell Res 2003; 289: 14351.
  • 26
    Murata S, Yoshiara T, Lim CR, Sugino M, Kogure M, Ohnuki T, Komurasaki T, Matsubara K. Psychophysiological stress-regulated gene expression in mice. FEBS Lett 2005; 579: 213742.
  • 27
    Takemasa I, Higuchi H, Yamamoto H, Sekimoto M, Tomita N, Nakamori S, Matoba R, Monden M, Matsubara K. Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer. Biochem Biophys Res Commun 2001; 285: 12449.
  • 28
    Finke J, Fritzen R, Ternes P, Lange W, Dolken G. An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. Biotechniques 1993; 14: 44853.
  • 29
    Miyamoto A, Nagano H, Sakon M, Fujiwara Y, Sugita Y, Eguchi H, Kondo M, Arai I, Morimoto O, Dono K, Umeshita K, Nakamori S, et al. Clinical application of quantitative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR. Int J Oncol 2001; 18: 52732.
  • 30
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors.European Organization for Research and Treatment of Cancer,National Cancer Institute of the United States,National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 20516.
  • 31
    Wright JA, Chan AK, Choy BK, Hurta RA, McClarty GA, Tagger AY. Regulation and drug resistance mechanisms of mammalian ribonucleotide reductase, and the significance to DNA synthesis. Biochem Cell Biol 1990; 68: 136471.
  • 32
    Hurta RA, Wright JA. Alterations in the activity and regulation of mammalian ribonucleotide reductase by chlorambucil, a DNA damaging agent. J Biol Chem 1992; 267: 706671.
  • 33
    Heinemann V, Xu YZ, Chubb S, Sen A, Hertel LW, Grindey GB, Plunkett W. Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2′,2′-difluorodeoxycytidine. Mol Pharmacol 1990; 38: 56772.
  • 34
    Jordan A, Reichard P. Ribonucleotide reductases. Annu Rev Biochem 1998; 67: 7198.
  • 35
    Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y. Wild-type p53 regulates human ribonucleotide reductase by protein–protein interaction with p53R2 as well as hRRM2 subunits. Cancer Res 2003; 63: 9806.
  • 36
    Eriksson S, Martin DW,Jr. Ribonucleotide reductase in cultured mouse lymphoma cells. Cell cycle-dependent variation in the activity of subunit protein M2. J Biol Chem 1981; 256: 943640.
  • 37
    Guittet O, Hakansson P, Voevodskaya N, Fridd S, Graslund A, Arakawa H, Nakamura Y, Thelander L. Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J Biol Chem 2001; 276: 4064751.
  • 38
    Giroux V, Malicet C, Barthet M, Gironella M, Archange C, Dagorn JC, Vasseur S, Iovanna JL. p8 is a new target of gemcitabine in pancreatic cancer cells. Clin Cancer Res 2006; 12: 23541.
  • 39
    Bepler G, Zheng Z, Gautam A, Sharma S, Cantor A, Sharma A, Cress WD, Kim YC, Rosell R, McBride C, Robinson L, Sommers E, et al. Ribonucleotide reductase M1 gene promoter activity, polymorphisms, population frequencies, and clinical relevance. Lung Cancer 2005; 47: 18392.
  • 40
    Jordheim LP, Guittet O, Lepoivre M, Galmarini CM, Dumontet C. Increased expression of the large subunit of ribonucleotide reductase is involved in resistance to gemcitabine in human mammary adenocarcinoma cells. Mol Cancer Ther 2005; 4: 126876.
  • 41
    Rosell R, Scagliotti G, Danenberg KD, Lord RV, Bepler G, Novello S, Cooc J, Crino L, Sanchez JJ, Taron M, Boni C, De Marinis F, et al. Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer. Oncogene 2003; 22: 354853.
  • 42
    Rosell R, Danenberg KD, Alberola V, Bepler G, Sanchez JJ, Camps C, Provencio M, Isla D, Taron M, Diz P, Artal A. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res 2004; 10: 131825.