REFERENCES
3. Burris H, Storniolo AM. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer 1997;33 Suppl 1:S18-22.
4. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, 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;15:2403-13.
5. Berlin J, Benson AB 3rd. Chemotherapy: gemcitabine remains the standard of care for pancreatic cancer. Nat Rev Clin Oncol 2010;7:135-7.
6. de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 2014;741:8-16.
7. Nakano Y, Tanno S, Koizumi K, Nishikawa T, Nakamura K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br J Cancer 2007;96:457-63.
8. Amrutkar M, Gladhaug IP. Pancreatic cancer chemoresistance to gemcitabine. Cancers (Basel) 2017;9.
9. Zeng S, Pottler M, Lan B, Grutzmann R, Pilarsky C, et al. Chemoresistance in Pancreatic Cancer. Int J Mol Sci 2019;20.
10. Cascioferro S, Petri GL, Parrino B, Carbone D, Funel N, et al. Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells. Eur J Med Chem 2020;189:112088.
11. Bhutia YD, Hung SW, Patel B, Lovin D, Govindarajan R. CNT1 expression influences proliferation and chemosensitivity in drug-resistant pancreatic cancer cells. Cancer Res 2011;71:1825-35.
12. Nordh S, Ansari D, Andersson R. hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: a systematic review. World J Gastroenterol 2014;20:8482-90.
13. Spratlin J, Sangha R, Glubrecht D, Dabbagh L, Young JD, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res 2004;10:6956-61.
14. Bergman AM, Pinedo HM, Peters GJ. Determinants of resistance to 2’,2’-difluorodeoxycytidine (gemcitabine). Drug Resist Updat 2002;5:19-33.
15. Sebastiani V, Ricci F, Rubio-Viqueira B, Kulesza P, Yeo CJ, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res 2006;12:2492-7.
16. Tibaldi C, Camerini A, Tiseo M, Mazzoni F, Barbieri F, et al. Cytidine deaminase enzymatic activity is a prognostic biomarker in gemcitabine/platinum-treated advanced non-small-cell lung cancer: a prospective validation study. Br J Cancer 2018;119:1326-31.
17. Liang C, Shi S, Meng Q, Liang D, Ji S, et al. Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going. Exp Mol Med 2017;49:e406.
18. 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;10:2307-18.
19. Ng SSW, Tsao MS, Chow S, Hedley DW. Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res 2000;60:5451-5.
20. Hu G, Li F, Ouyang K, Xie F, Tang X, et al. Intrinsic gemcitabine resistance in a novel pancreatic cancer cell line is associated with cancer stem cell-like phenotype. Int J Oncol 2012;40:798-806.
21. Vaz AP, Ponnusamy MP, Seshacharyulu P, Batra SK. A concise review on the current understanding of pancreatic cancer stem cells. J Cancer Stem Cell Res 2014;2.
22. Singh S, Srivastava SK, Bhardwaj A, Owen LB, Singh AP. CXCL12-CXCR4 signalling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy. Br J Cancer 2010;103:1671-9.
23. Schniewind B, Christgen M, Kurdow R, Haye S, Kremer B, et al. Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria-mediated apoptosis. Int J Cancer 2004;109:182-8.
24. Shi X, Liu S, Kleeff J, Friess H, Buchler MW. Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes. Oncology 2002;62:354-62.
25. Garcia PL, Council LN, Christein JD, Arnoletti JP, Heslin MJ, et al. Development and histopathological characterization of tumorgraft models of pancreatic ductal adenocarcinoma. PLoS One 2013;8:e78183.
26. Jin K, Teng L, Shen Y, He K, Xu Z, et al. Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review. Clin Transl Oncol 2010;12:473-80.
27. Morelli MP, Calvo E, Ordonez E, Wick MJ, Viqueira BR, et al. Prioritizing phase I treatment options through preclinical testing on personalized tumorgraft. J Clin Oncol 2012;30:e45-8.
28. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703.
29. Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol 2012;9:338-50.
30. Garcia PL, Miller AL, Kreitzburg KM, Council LN, Gamblin TL, et al. The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene 2016;35:833-45.
31. Garcia PL, Miller AL, Gamblin TL, Council LN, Christein JD, et al. JQ1 induces DNA damage and apoptosis, and inhibits tumor growth in a patient-derived xenograft model of cholangiocarcinoma. Mol Cancer Ther 2018;17:107-18.
32. Miller AL, Fehling SC, Garcia PL, Gamblin TL, Council LN, et al. The BET inhibitor JQ1 attenuates double-strand break repair and sensitizes models of pancreatic ductal adenocarcinoma to PARP inhibitors. EBioMedicine 2019;44:419-30.
33. Kreitzburg KM, Fehling SC, Landen CN, Gamblin TL, Vance RB, et al. FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer. Cancer Lett 2018;436:75-86.
34. Houghton PJ, Morton CL, Tucker C, Payne D, Favours E, et al. The pediatric preclinical testing program: description of models and early testing results. Pediatr Blood Cancer 2007;49:928-40.
35. Samulitis BK, Pond KW, Pond E, Cress AE, Patel H, et al. Gemcitabine resistant pancreatic cancer cell lines acquire an invasive phenotype with collateral hypersensitivity to histone deacetylase inhibitors. Cancer Biol Ther 2015;16:43-51.
36. Davidson JD, Ma L, Flagella M, Geeganage S, Gelbert LM, et al. 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;64:3761-6.
37. Jonckheere N, Skrypek N, Merlin J, Dessein AF, Dumont P, et al. The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of human CAPAN-2 pancreatic cancer cells via different signalling pathways. PLoS One 2012;7:e32232.
38. Minami K, Shinsato Y, Yamamoto M, Takahashi H, Zhang S, et al. Ribonucleotide reductase is an effective target to overcome gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells with dual resistant factors. J Pharmacol Sci 2015;127:319-25.
39. Wang C, Zhang W, Fu M, Yang A, Huang H, et al. Establishment of human pancreatic cancer gemcitabineresistant cell line with ribonucleotide reductase overexpression. Oncol Rep 2015;33:383-90.
40. Achiwa H, Oguri T, Sato S, Maeda H, Niimi T, et al. 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 2004;95:753-7.
41. Garcia-Manteiga J, Molina-Arcas M, Casado FJ, Mazo A, Pastor-Anglada M. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2’,2’-difluorodeoxycytidine- induced cytotoxicity. Clin Cancer Res 2003;9:5000-8.
42. Mackey JR, Mani RS, Selner M, Mowles D, Young JD, et al. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res 1998;58:4349-57.
43. Neff T, Blau CA. Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine. Exp Hematol 1996;24:1340-6.
44. Ohhashi S, Ohuchida K, Mizumoto K, Fujita H, Egami T, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. Anticancer Res 2008;28:2205-12.
45. Saiki Y, Yoshino Y, Fujimura H, Manabe T, Kudo Y, et al. DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells. Biochem Biophys Res Commun 2012;421:98-104.
46. Weizman N, Krelin Y, Shabtay-Orbach A, Amit M, Binenbaum Y, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene 2014;33:3812-9.
47. Gzil A, Zarebska I, Bursiewicz W, Antosik P, Grzanka D, et al. Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep 2019;46:6629-45.
48. Sergeant G, Vankelecom H, Gremeaux L, Topal B. Role of cancer stem cells in pancreatic ductal adenocarcinoma. Nat Rev Clin Oncol 2009;6:580-6.
49. Duong HQ, Hwang JS, Kim HJ, Kang HJ, Seong YS, et al. Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. Int J Oncol 2012;41:855-61.
50. van Diest PJ, van der Wall E, Baak JP. Prognostic value of proliferation in invasive breast cancer: a review. J Clin Pathol 2004;57:675-81.
51. Hausser HJ, Brenner RE. Phenotypic instability of Saos-2 cells in long-term culture. Biochem Biophys Res Commun 2005;333:216-22.
52. Kelland LR. Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development. Eur J Cancer 2004;40:827-36.
53. Bergman AM, Eijk PP, Ruiz van Haperen VW, Smid K, Veerman G, et al. In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant. Cancer Res 2005;65:9510-6.
54. Corbett TH, Griswold DP Jr., Roberts BJ, Peckham JC, Schabel FM Jr. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res 1975;35:2434-9.
55. Peters GJ, Van Dijk J, Nadal JC, Van Groeningen CJ, Lankelma J, et al. Diurnal variation in the therapeutic efficacy of 5-fluorouracil against murine colon cancer. In Vivo 1987;1:113-7.
56. Ter Brugge P, Kristel P, van der Burg E, Boon U, de Maaker M, et al. Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. J Natl Cancer Inst 2016;108.
