吉西他濱代謝酶與胰腺癌化療耐藥關系的研究進展_《中國普外基礎與臨床雜志》

作者：

袁田 ^1,2 , 廖泉 ² , 趙玉沛 ²

1.中國醫學科學院北京協和醫學院（北京 100730）;;
2.中國醫學科學院北京協和醫院基本外科（北京 100730）;

關鍵詞：

胰腺癌吉西他濱代謝酶耐藥性化療

視頻：

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目的介紹吉西他濱代謝酶對胰腺癌化療耐藥影響的研究進展。
方法復習和總結了近年來的相關文獻，對吉西他濱代謝酶與胰腺癌化療耐藥關系的研究進展加以綜述。
結果 hENT1、dCK、RRM1、CDA等代謝酶與胰腺癌對吉西他濱化療的耐藥具有密切關系；代謝酶的單核苷酸多態性與胰腺癌對吉西他濱耐藥的關系仍有待研究。
結論胰腺癌對吉西他濱化療耐藥是多因素、多因子共同作用的結果，對于代謝酶影響胰腺癌化療耐藥的機理有待進一步研究。

引用本文： 袁田,廖泉,趙玉沛. 吉西他濱代謝酶與胰腺癌化療耐藥關系的研究進展. 中國普外基礎與臨床雜志, 2009, 16(8): 613-616. doi: 復制

1.	Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer [Ｊ]. Br J Surg, 2004; 91(11): 1410-1427.
2.	Abbruzzese JL. New applications of gemcitabine and future directions in the management of pancreatic cancer [Ｊ]. Cancer, 2002; 95 (4 Suppl): 941-945.
3.	Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial [Ｊ]. J Clin Oncol, 1997; 15(6): 2403-2413.
4.	Mini E, Nobili S, Caciagli B, et al. Cellular pharmacology of gemcitabine [Ｊ]. Ann Oncol, 2006; 17 (Suppl 5): v7-v12.
5.	Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: mechanisms of drug resistance and reversal strategies [Ｊ]. Leukemia, 2001; 15(6): 875-890.
6.	Shi JY, Shi ZZ, Zhang SJ, et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients [Ｊ]. Pharmacogenetics, 2004; 14(11): 759-768.
7.	Ward JL, Leung GP, Toan SV, et al. Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2 [Ｊ]. Arch Biochem Biophys, 2003; 411(1): 19-26.
8.	García-Manteiga J, Molina-Arcas M, Casado FJ, et al. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2’, 2’-difluorodeoxycytidine-induced cytotoxicity [Ｊ]. Clin Cancer Res, 2003; 9(13): 5000-5008.
9.	Mori R, Ishikawa T, Ichikawa Y, et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells [Ｊ]. Oncol Rep, 2007; 17(5): 1201-1205.
10.	Rauchwerger DR, Firby PS, Hedley DW, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity [Ｊ]. Cancer Res, 2000; 60(21): 6075-6079.
11.	Giovannetti E, Del Tacca M, Mey V, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine [Ｊ]. Cancer Res, 2006; 66(7): 3928-3935.
12.	Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer [Ｊ]. Gastroenterology, 2009; 136(1): 187-195.
13.	Spratlin J, Sangha R, Darry Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma [Ｊ]. Clin Cancer Res, 2004; 10(20): 6956-6961.
14.	Giovannetti E, Mey V, Nannizzi S, et al. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer [Ｊ]. Mol Cancer Ther, 2006; 5(6): 1387-1395.
15.	Kroep JR, Loves WJ, van der Wilt CL, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity [Ｊ]. Mol Cancer Ther, 2002; 1(6): 371-376.
16.	Blackstock AW, Lightfoot H, Case LD, et al. Tumor uptake and elimination of 2’, 2’-difluoro-2’-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response [Ｊ]. Clin Cancer Res, 2001; 7(10): 3263-3268.
17.	Veuger MJ, Heemskerk MH, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells [Ｊ]. Blood, 2002; 99(4): 1373-1380.
18.	Veuger MJ, Honders MW, Landegent JE, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia [Ｊ]. Blood, 2000; 96(4): 1517-1524.
19.	Galmarini CM, Clarke ML, Jordheim L, et al. Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene [Ｊ]. BMC Pharmacol, 2004; 4: 8-20.
20.	Ohhashi S, Ohuchida K, Mizumoto K, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer [Ｊ]. Anticancer Res, 2008; 28(4B): 2205-2212.
21.	Szantai E, Ronai Z, Sasvari-Szekely M, et al. Multicapillary electrophoresis analysis of single-nucleotide sequence variations in the deoxycytidine kinase gene [Ｊ]. Clin Chem, 2006; 52(9): 1756-1762.
22.	Sebastiani V, Ricci F, Rubio-Viqueira B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival [Ｊ]. Clin Cancer Res, 2006; 12(8): 2492-2497.
23.	Davidson JD, Ma L, Flagella M, 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 [Ｊ]. Cancer Res, 2004; 64(11): 3761-3766.
24.	Bergman AM, Eijk PP, Ruiz van Haperen VW, et al. In vivo induction of resistance to gemcitabine resultsin increased expression of ribonucleotide reductase subunit M1 as the major determinant [Ｊ]. Cancer Res, 2005; 65(20): 9510-9516.
25.	Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling [Ｊ]. Electrophoresis, 1997; 18(15): 2714-2723.
26.	Yonemori K, Ueno H, Okusaka T, et al. Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin [Ｊ]. Clin Cancer Res, 2005; 11(7): 2620-2624.
27.	Sugiyama E, Kaniwa N, Kim SR, et al. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism [Ｊ]. J Clin Oncol, 2007; 25(1): 32-42.
28.	Nakano Y, Tanno S, Koizumi K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells [Ｊ]. Br J Cancer, 2007; 96(3): 457-463.
29.	張立陽，趙玉沛，吳元德，等. 胰腺癌阿霉素耐藥細胞株SW1990/ADM的建立及其耐藥機理研究 [Ｊ]. 中國普外基礎與臨床雜志， 2005； 12（1）： 46-50.
30.	潘博，郭俊超，廖泉，等. 吉西他濱與胰腺癌化療耐藥 [Ｊ]. 中國普外基礎與臨床雜志， 2005； 12（5）： 530-532.

1. Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer [Ｊ]. Br J Surg, 2004; 91(11): 1410-1427.
2. Abbruzzese JL. New applications of gemcitabine and future directions in the management of pancreatic cancer [Ｊ]. Cancer, 2002; 95 (4 Suppl): 941-945.
3. Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial [Ｊ]. J Clin Oncol, 1997; 15(6): 2403-2413.
4. Mini E, Nobili S, Caciagli B, et al. Cellular pharmacology of gemcitabine [Ｊ]. Ann Oncol, 2006; 17 (Suppl 5): v7-v12.
5. Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: mechanisms of drug resistance and reversal strategies [Ｊ]. Leukemia, 2001; 15(6): 875-890.
6. Shi JY, Shi ZZ, Zhang SJ, et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients [Ｊ]. Pharmacogenetics, 2004; 14(11): 759-768.
7. Ward JL, Leung GP, Toan SV, et al. Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2 [Ｊ]. Arch Biochem Biophys, 2003; 411(1): 19-26.
8. García-Manteiga J, Molina-Arcas M, Casado FJ, et al. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2’, 2’-difluorodeoxycytidine-induced cytotoxicity [Ｊ]. Clin Cancer Res, 2003; 9(13): 5000-5008.
9. Mori R, Ishikawa T, Ichikawa Y, et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells [Ｊ]. Oncol Rep, 2007; 17(5): 1201-1205.
10. Rauchwerger DR, Firby PS, Hedley DW, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity [Ｊ]. Cancer Res, 2000; 60(21): 6075-6079.
11. Giovannetti E, Del Tacca M, Mey V, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine [Ｊ]. Cancer Res, 2006; 66(7): 3928-3935.
12. Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer [Ｊ]. Gastroenterology, 2009; 136(1): 187-195.
13. Spratlin J, Sangha R, Darry Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma [Ｊ]. Clin Cancer Res, 2004; 10(20): 6956-6961.
14. Giovannetti E, Mey V, Nannizzi S, et al. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer [Ｊ]. Mol Cancer Ther, 2006; 5(6): 1387-1395.
15. Kroep JR, Loves WJ, van der Wilt CL, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity [Ｊ]. Mol Cancer Ther, 2002; 1(6): 371-376.
16. Blackstock AW, Lightfoot H, Case LD, et al. Tumor uptake and elimination of 2’, 2’-difluoro-2’-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response [Ｊ]. Clin Cancer Res, 2001; 7(10): 3263-3268.
17. Veuger MJ, Heemskerk MH, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells [Ｊ]. Blood, 2002; 99(4): 1373-1380.
18. Veuger MJ, Honders MW, Landegent JE, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia [Ｊ]. Blood, 2000; 96(4): 1517-1524.
19. Galmarini CM, Clarke ML, Jordheim L, et al. Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene [Ｊ]. BMC Pharmacol, 2004; 4: 8-20.
20. Ohhashi S, Ohuchida K, Mizumoto K, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer [Ｊ]. Anticancer Res, 2008; 28(4B): 2205-2212.
21. Szantai E, Ronai Z, Sasvari-Szekely M, et al. Multicapillary electrophoresis analysis of single-nucleotide sequence variations in the deoxycytidine kinase gene [Ｊ]. Clin Chem, 2006; 52(9): 1756-1762.
22. Sebastiani V, Ricci F, Rubio-Viqueira B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival [Ｊ]. Clin Cancer Res, 2006; 12(8): 2492-2497.
23. Davidson JD, Ma L, Flagella M, 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 [Ｊ]. Cancer Res, 2004; 64(11): 3761-3766.
24. Bergman AM, Eijk PP, Ruiz van Haperen VW, et al. In vivo induction of resistance to gemcitabine resultsin increased expression of ribonucleotide reductase subunit M1 as the major determinant [Ｊ]. Cancer Res, 2005; 65(20): 9510-9516.
25. Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling [Ｊ]. Electrophoresis, 1997; 18(15): 2714-2723.
26. Yonemori K, Ueno H, Okusaka T, et al. Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin [Ｊ]. Clin Cancer Res, 2005; 11(7): 2620-2624.
27. Sugiyama E, Kaniwa N, Kim SR, et al. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism [Ｊ]. J Clin Oncol, 2007; 25(1): 32-42.
28. Nakano Y, Tanno S, Koizumi K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells [Ｊ]. Br J Cancer, 2007; 96(3): 457-463.
29. 張立陽，趙玉沛，吳元德，等. 胰腺癌阿霉素耐藥細胞株SW1990/ADM的建立及其耐藥機理研究 [Ｊ]. 中國普外基礎與臨床雜志， 2005； 12（1）： 46-50.
30. 潘博，郭俊超，廖泉，等. 吉西他濱與胰腺癌化療耐藥 [Ｊ]. 中國普外基礎與臨床雜志， 2005； 12（5）： 530-532.

《中國普外基礎與臨床雜志》

吉西他濱代謝酶與胰腺癌化療耐藥關系的研究進展

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《中國普外基礎與臨床雜志》

吉西他濱代謝酶與胰腺癌化療耐藥關系的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料