進階搜尋


  查詢北醫館藏
系統識別號 U0007-1507201112090900
論文名稱(中文) 於接受Cisplatin或Carboplatin治療之肺癌病人運用基因及非基因因子進行腎毒性之多元分析
論文名稱(英文) Multiple Analytical Approaches Demonstrate a Complex Relationship of Genetic and Nongenetic Factors with Cisplatin- or Carboplatin-induced Nephrotoxicity in Lung Cancer Patients
校院名稱 臺北醫學大學
系所名稱(中) 藥學研究所
系所名稱(英) Graduate Institute of Pharmacy
學年度 99
學期 2
出版年 100
研究生(中文) 謝雨純
研究生(英文) Yu-Chen Hsieh
電子信箱 kangta571315@hotmail.com
學號 M301098002
學位類別 碩士
語文別 中文
口試日期 2011-06-24
論文頁數 82頁
口試委員 指導教授-陳香吟
委員-邱弘毅
委員-黃文鴻
中文關鍵字 cisplatin  carboplatin  腎毒性  基因多型性  CART 
英文關鍵字 cisplatin  carboplatin  nephrotoxicity  polymorphisms  CART 
學科別分類
中文摘要 Cisplatin及carboplatin是目前使用最廣泛的化學治療藥物,為許多固態腫瘤之第一線用藥。然而,腎毒性限制了這類藥物的使用,約有三分之一病人即使給予適當的輸液還是會發生。Cisplatin或carboplatin所引起腎毒性之機轉推測可能為多條路經交互作用之結果,這些路徑包括增加攝入細胞、腎毒性物質之形成、ROS過度累積、DNA修復能力受損及細胞凋亡。本研究一共納入116位接受cisplatin或carboplatin治療之肺癌病人,擬探討台灣族群的7 個基因共11個基因多型性(GSTPi A313G, TP53 G215C, UGT1A7 T387G, UGT1A7 T622C, NAT2 T481C, NAT2 G590A, NAT2 G857A, ERCC1 C118T, ERCC1 C8092A, ERCC4 T2505C and NQO1 C609T)與使用cisplatin及carboplatin引起腎毒性之關聯性,並建立腎毒性預測模型,尋找腎毒性之易感族群。本研究採Risk, Injury, Failure, Loss of function, End-stage renal disease(RIFLE)準則評估腎毒性之發生有無。並以classification and regression tree(CART)及Framingham study risk score建立腎毒性預測模型,探討基因與非基因因子,及其之間交互作用對腎毒性之重要性。結果發現在男性研究對象中,帶有TP53對偶基因者出現腎毒性風險較野生型顯著下降(OR =0.12, 95%CI 0.02-0.81)。此外,主要使用cisplatin治療之病人,帶有ERCC1 118T基因型亦有同樣趨勢(OR =0.14, 95%CI 0.03-0.72)。CART所建立之預測模型發現,主要使用cisplatin且Scr≦1mg/dL之病人,帶有TP53野生型或TP53 G對偶基因-ERCC1 C118T 野生型者為腎毒性之易感族群。此模型可預測63.0%腎毒性組、89.6%無腎毒性組。另一預測模型,腎毒性危險因子評估量表,顯示同時含有基因及非基因因子時,有最好預測性,評量表之最佳切點為12分,可預測64.3%腎毒性組、90.9%無腎毒性組。本研究顯示男性且帶有TP53 G對偶基因或使用cisplatin者帶有ERCC1 C118T C對偶基因可能為腎毒性之危險因子。累積治療次數及cisplatin累積給藥強度亦可能為腎毒性之危險因子。然而,基於臨床實用性考量,以CART預測模型較腎毒性危險因子評量表佳,以納入較少的因子達相近的預測力。
英文摘要 Introduction: The purpose of this study was to investigate the association between the cisplatin- or carboplatin-induced nephrotoxicity and the multiple single nucleotide polymorphisms (SNPs). Multiple statistical methods including genetic and nongenetic factors were applied to establish clinical useful model for predicting the cisplatin- or carboplatin-induced nephrotoxicity. Patients and Methods: The retrospective study investigated 11 polymorphisms in 7 genes (GSTPi A313G, TP53 G215C, UGT1A7 T387G/T622C, NAT2 T481C/G590A/G857A, ERCC1 C118T/C8092A, ERCC4 T2505C and NQO1 C609T) in 116 Taiwanese patients who had received cisplatin or carboplatin more than twice for lung cancer at Wanfang Hospital. The Risk, Injury, Failure, Loss of function, End-stage renal disease (RIFLE) criteria was use to evaluate the occurrence of nephrotoxicity. Multiple regression with classification and regression tree (CART) and Framingham study risk score were used to study the interactions between the genetic and nongenetic factors with cisplatin- or carboplatin-induced nephrotoxicity. Results: In logistic regression, the male patients carrying TP53 C allele had lower risk of nephrotoxicity (OR =0.12, 95%CI = 0.02-0.81). Subgroup analysis on cisplatin, patients revealed that ERCC1 T allele at 118 also had protective effects in nephrotoxicity (OR =0.14, 95%CI = 0.03-0.72). In CART analysis, individuals who were using cisplatin and baseline serum creatinie ≦1mg/dL with TP53 Arg/Arg or TP53 Pro allele-ERCC1 C/C were higher nephrotoxicity risk. The overall prediction rate of CART was 82.7%. The sensitivity and specificity are 0.630 and 0.896, respectively. Another prediction model, according to Framingham study risk score, was contained 7 factors. Its overall prediction rate was 84.5%. The sensitivity and specificity were 0.643 and 0.909, respectively. Conclusion: We found that genes, TP53 Arg72Pro and ERCC1 C118T, might be the risk factors of nephrotoxicity. Because of containing fewer factors and equal prediction rate, the results suggest that CART model was better than nephrotoxicity risk score. In addition to simultaneously containing the genetic and nongenetic factors, a favor model to predict the cisplatin- or carboplatin-induced nephrotoxicity also had to take interaction of these factors in consideration.
論文目次 第1章 緒論 1
第2章 文獻探討 2
2.1 CISPLATIN及CARBOPLATIN簡介 2
2.1.1 Cisplatin及carboplatin之作用機轉 2
2.1.2 Cisplatin及carboplatin之藥物動力學 3
2.1.3 Cisplatin及carboplatin之使用療程 3
2.1.4 Cisplatin及carboplatin除腎毒性外常見副作用 4
2.2 CISPLATIN及CARBOPLATIN之腎毒性 6
2.2.1 Cisplatin及carboplatin所引起腎毒性之臨床表徵 6
2.2.2 Cisplatin及carboplatin所引起腎毒性之病因學 6
2.2.3 Cisplatin及carboplatin所引起腎毒性之危險因子 7
2.2.4 腎毒性預防措施 7
2.3 CISPLATIN及CARBOPLATIN所引起腎毒性之分子機轉 8
2.4 CISPLATIN及CARBOPLATIN引起腎毒性相關基因文獻回顧 12
2.4.1 NAD(P)H:dehydrogenase quinone (NQO) 1 12
2.4.2 Glutathione S-transferase (GST) Pi 12
2.4.3 N-aceyltransferase (NAT) 2 14
2.4.4 Uridine-diphosphoglucuronosyltransferase (UGT) 1A7 15
2.4.5 Excision repair cross-complementing (ERCC) 1/4 15
2.4.6 Tumor supressor protein 53 (TP53) 18
2.5 其他腎毒性相關基因之文獻回顧 20
2.5.1 Tumor necrosis factor-α (TNF-α) 20
2.5.2 Organic cation transporter (OCT) 2 20
2.5.3 Xeroderma pigmentosum group (XP) D 20
2.6 CLASSIFICATION AND REGRESSION TREE (CART)簡介 21
第3章 研究目的 23
第4章 研究方法 24
4.1 研究設計 24
4.1.1 病人描述 24
4.1.2 病歷資料收集 25
4.1.3 研究相關定義 25
4.2 基因型檢測 27
4.2.1 DNA萃取 27
4.2.2 高效能液相層析儀(DHPLC)分析 28
4.2.3 限制?﹞螺?(RFLE-PCR) 32
4.2.4 TaqMan SNP Genotyping Assay 34
4.2.5 確效(Validation) 36
4.3 統計方法 37
第5章 研究結果 38
5.1 基本資料分析 38
5.2 單核?˙襤穧]型分析 40
5.2.1 Hardy-Weinberg平衡 40
5.3 單核?˙襤穧]型與腎毒性關聯分析 41
5.3.1 對偶基因頻率(allele frequency)與腎毒性關聯分析 41
5.3.2 單核?˙襤穧]型與腎毒性關聯分析 42
5.3.3 性別差異 42
5.3.4 Cisplatin次族群分析 46
5.4 給藥因子與腎毒性關聯分析 48
5.5 CLASSIFICATION AND REGRESSION TREE ANALYSIS 49
5.6 腎毒性危險因子評估量表-1 52
5.6.1 腎毒性危險因子評估量表-1之模型正確性評估 53
5.6.2 腎毒性危險因子評估量表-1之模型預測百分比 54
5.7 腎毒性危險因子評估量表-2 56
5.7.1 腎毒性危險因子評估量表-2之模型正確性評估 56
5.7.2 腎毒性危險因子評估量表-2之模型預測百分比 57
5.8 不同基因型之CISPLATIN累積給藥強度與腎毒性之關聯 59
第6章 討論 62
6.1 研究結果討論 62
6.1.1 腎毒性發生率 62
6.1.2 單一基因多型性與腎毒性之關聯 63
6.1.3 其他腎毒性危險因子 68
6.2 多基因交互作用分析 70
6.2.1 Classification and Regression Tree 70
6.2.2 腎毒性危險因子評估量表-1 71
6.2.3 腎毒性危險因子評估量表-2 71
6.2.4 CART與腎毒性危險因子評量表之結果比較 71
6.3 研究限制與未來改進方向討論 73
第7章 結論 75
參考文獻 77
參考文獻 1. Rosenberg, B., et al., Platinum compounds: a new class of potent antitumour agents. Nature, 1969. 222(5191): p. 385-6.
2. Kelland, L., The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer, 2007. 7(8): p. 573-84.
3. Kostova, I., Platinum complexes as anticancer agents. Recent Pat Anticancer Drug Discov, 2006. 1(1): p. 1-22.
4. DeConti, R.C., et al., Clinical and pharmacological studies with cis-diamminedichloroplatinum (II). Cancer Res, 1973. 33(6): p. 1310-5.
5. Ardizzoni, A., et al., Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst, 2007. 99(11): p. 847-57.
6. cisplatin: drug information. Available from: http://www.uptodate.com/contents/cisplatin-drug-information?source=search_result&selectedTitle=1%7E150#F151883.
7. Hartmann, J.T. and H.P. Lipp, Toxicity of platinum compounds. Expert Opin Pharmacother, 2003. 4(6): p. 889-901.
8. Jodrell, D.I., Formula-based dosing for carboplatin. Eur J Cancer, 1999. 35(9): p. 1299-301.
9. Calvert, A.H., et al., Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol, 1989. 7(11): p. 1748-56.
10. Markman, M., Toxicities of the platinum antineoplastic agents. Expert Opin Drug Saf, 2003. 2(6): p. 597-607.
11. Lokich, J. and N. Anderson, Carboplatin versus cisplatin in solid tumors: an analysis of the literature. Ann Oncol, 1998. 9(1): p. 13-21.
12. McWhinney, S.R., R.M. Goldberg, and H.L. McLeod, Platinum neurotoxicity pharmacogenetics. Mol Cancer Ther, 2009. 8(1): p. 10-6.
13. Dzagnidze, A., et al., Repair capacity for platinum-DNA adducts determines the severity of cisplatin-induced peripheral neuropathy. J Neurosci, 2007. 27(35): p. 9451-7.
14. Windebank, A.J. and W. Grisold, Chemotherapy-induced neuropathy. J Peripher Nerv Syst, 2008. 13(1): p. 27-46.
15. Bokemeyer, C., et al., Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Br J Cancer, 1998. 77(8): p. 1355-62.
16. Oldenburg, J., S.D. Fossa, and T. Ikdahl, Genetic variants associated with cisplatin-induced ototoxicity. Pharmacogenomics, 2008. 9(10): p. 1521-30.
17. Li, Y., R.B. Womer, and J.H. Silber, Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer, 2004. 40(16): p. 2445-51.
18. Goren, M.P., Cisplatin nephrotoxicity affects magnesium and calcium metabolism. Med Pediatr Oncol, 2003. 41(3): p. 186-9.
19. Taguchi, T., et al., Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol, 2005. 148: p. 107-21.
20. Yao, X., et al., Cisplatin nephrotoxicity: a review. Am J Med Sci, 2007. 334(2): p. 115-24.
21. Skinner, R., et al., Cisplatin dose rate as a risk factor for nephrotoxicity in children. Br J Cancer, 1998. 77(10): p. 1677-82.
22. Siegert, W., et al., High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group. J Clin Oncol, 1994. 12(6): p. 1223-31.
23. Caglar, K., et al., Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation. Nephrol Dial Transplant, 2002. 17(11): p. 1931-5.
24. de Jongh, F.E., et al., Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer, 2003. 88(8): p. 1199-206.
25. Launay-Vacher, V., et al., Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol, 2008. 61(6): p. 903-9.
26. Santoso, J.T., et al., Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: a randomized trial. Cancer Chemother Pharmacol, 2003. 52(1): p. 13-8.
27. Hildebrandt, M.A., J. Gu, and X. Wu, Pharmacogenomics of platinum-based chemotherapy in NSCLC. Expert Opin Drug Metab Toxicol, 2009. 5(7): p. 745-55.
28. Ishida, S., et al., Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci U S A, 2002. 99(22): p. 14298-302.
29. Blair, B.G., et al., Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res, 2009. 15(13): p. 4312-21.
30. Motohashi, H., et al., Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol, 2002. 13(4): p. 866-74.
31. Filipski, K.K., et al., Interaction of Cisplatin with the human organic cation transporter 2. Clin Cancer Res, 2008. 14(12): p. 3875-80.
32. Filipski, K.K., et al., Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. Clin Pharmacol Ther, 2009. 86(4): p. 396-402.
33. Arthur J. L. Cooper, J.T.P., Advances in Bioactivation Research. 2008: Springer New York.
34. Townsend, D.M., et al., Metabolism of Cisplatin to a nephrotoxin in proximal tubule cells. J Am Soc Nephrol, 2003. 14(1): p. 1-10.
35. Kolb, R.J., A.M. Ghazi, and D.W. Barfuss, Inhibition of basolateral transport and cellular accumulation of cDDP and N-acetyl- L-cysteine-cDDP by TEA and PAH in the renal proximal tubule. Cancer Chemother Pharmacol, 2003. 51(2): p. 132-8.
36. Wang, J., et al., Caspase-mediated cleavage of ATM during cisplatin-induced tubular cell apoptosis: inactivation of its kinase activity toward p53. Am J Physiol Renal Physiol, 2006. 291(6): p. F1300-7.
37. Pabla, N., et al., ATR-Chk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. J Biol Chem, 2008. 283(10): p. 6572-83.
38. Jiang, M., et al., Effects of hydroxyl radical scavenging on cisplatin-induced p53 activation, tubular cell apoptosis and nephrotoxicity. Biochem Pharmacol, 2007. 73(9): p. 1499-510.
39. Wu, Y.J., L.L. Muldoon, and E.A. Neuwelt, The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J Pharmacol Exp Ther, 2005. 312(2): p. 424-31.
40. Jiang, M., et al., Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway. Am J Physiol Renal Physiol, 2009. 296(5): p. F983-93.
41. Dinkova-Kostova, A.T. and P. Talalay, NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch Biochem Biophys, 2010. 501(1): p. 116-23.
42. Siegel, D., et al., Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone oxidoreductase 1. Pharmacogenetics, 1999. 9(1): p. 113-21.
43. Kiyohara, C., et al., NQO1, MPO, and the risk of lung cancer: a HuGE review. Genet Med, 2005. 7(7): p. 463-78.
44. Chao, C., et al., NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis. Cancer Epidemiol Biomarkers Prev, 2006. 15(5): p. 979-87.
45. Nebert, D.W., et al., NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review. Genet Med, 2002. 4(2): p. 62-70.
46. Zappa, F., et al., NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes. J Histochem Cytochem, 2003. 51(3): p. 297-302.
47. Guerrero-Beltran, C.E., et al., Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and gamma glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells. Toxicol Lett, 2010. 199(1): p. 80-92.
48. Lo, H.W. and F. Ali-Osman, Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr Opin Pharmacol, 2007. 7(4): p. 367-74.
49. Lin, P., et al., Analysis of NQO1, GSTP1, and MnSOD genetic polymorphisms on lung cancer risk in Taiwan. Lung Cancer, 2003. 40(2): p. 123-9.
50. 石凱文, 麩胱甘?汕鉦???-Pi(GSTP1)基因多型性與Cisplatin或Carboplatin所引起腎毒性之關聯研究. 台北醫學大學, 99年.
51. Townsend, D.M., et al., Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity. Biomed Pharmacother, 2009. 63(2): p. 79-85.
52. Goekkurt, E., et al., Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: a study of the arbeitsgemeinschaft internistische onkologie. J Clin Oncol, 2009. 27(17): p. 2863-73.
53. Khrunin, A.V., et al., Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. Pharmacogenomics J, 2010. 10(1): p. 54-61.
54. Huang, Y.S., et al., Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology, 2002. 35(4): p. 883-9.
55. 張淑惠, 建立預測抗結核藥物治療期間肝損傷之評分系統暨評估基因型危險因子之重要性. 台北醫學大學, 97年.
56. 黃薇伊, 尿??雙磷酸葡萄醣醛酸基轉移??1A7(UGT1A7)基因型與肺癌之關聯研究. 台北醫學大學, 98年.
57. Huang, M.J., et al., Polymorphisms of uridine-diphosphoglucuronosyltransferase 1A7 gene in Taiwan Chinese. World J Gastroenterol, 2005. 11(6): p. 797-802.
58. Han, J.Y., et al., Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol, 2006. 24(15): p. 2237-44.
59. Yin, M., et al., No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: A meta-analysis. Lung Cancer, 2011. 72(3): p. 370-7.
60. Vilmar, A. and J.B. Sorensen, Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer, 2009. 64(2): p. 131-9.
61. Tibaldi, C., et al., Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res, 2008. 14(6): p. 1797-803.
62. Suk, R., et al., Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients. Clin Cancer Res, 2005. 11(4): p. 1534-8.
63. Dumont, P., et al., The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet, 2003. 33(3): p. 357-65.
64. Wei, Q., et al., Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol, 2007. 293(4): p. F1282-91.
65. Xiao, T., et al., Possible involvement of oxidative stress in cisplatin-induced apoptosis in LLC-PK1 cells. J Toxicol Environ Health A, 2003. 66(5): p. 469-79.
66. Jiang, M., et al., Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity. Am J Physiol Renal Physiol, 2004. 287(6): p. F1140-7.
67. Yang, C., et al., Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity. Cell Death Differ, 2008. 15(3): p. 530-44.
68. Kang, K.P., et al., Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant, 2011. 26(3): p. 814-22.
69. Cummings, B.S. and R.G. Schnellmann, Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther, 2002. 302(1): p. 8-17.
70. Molitoris, B.A., et al., siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc Nephrol, 2009. 20(8): p. 1754-64.
71. Dong, Z. and S.S. Atherton, Tumor necrosis factor-alpha in cisplatin nephrotoxicity: a homebred foe? Kidney Int, 2007. 72(1): p. 5-7.
72. Zhang, B., et al., Cisplatin-induced nephrotoxicity is mediated by tumor necrosis factor-alpha produced by renal parenchymal cells. Kidney Int, 2007. 72(1): p. 37-44.
73. Tsuruya, K., et al., Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Kidney Int, 2003. 63(1): p. 72-82.
74. Ramesh, G. and W.B. Reeves, TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. Am J Physiol Renal Physiol, 2003. 285(4): p. F610-8.
75. Ramesh, G. and W.B. Reeves, TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest, 2002. 110(6): p. 835-42.
76. Ramesh, G. and W.B. Reeves, Inflammatory cytokines in acute renal failure. Kidney Int Suppl, 2004(91): p. S56-61.
77. Lewis, R.J., An introduction to classification and regression tree(CART) analysis. annual meeting of the society for academic emergency medicine in San Francisco, California, 2000.
78. Yang, H., et al., Genetic polymorphisms in double-strand break DNA repair genes associated with risk of oral premalignant lesions. Eur J Cancer, 2008. 44(11): p. 1603-11.
79. Chan, J.Y., et al., Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children. Hematol Oncol, 2010.
80. Chen, M., et al., High-order interactions among genetic polymorphisms in nucleotide excision repair pathway genes and smoking in modulating bladder cancer risk. Carcinogenesis, 2007. 28(10): p. 2160-5.
81. Huang, M., et al., High-order interactions among genetic variants in DNA base excision repair pathway genes and smoking in bladder cancer susceptibility. Cancer Epidemiol Biomarkers Prev, 2007. 16(1): p. 84-91.
82. Wu, X., et al., Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet, 2006. 78(3): p. 464-79.
83. Wu, X., et al., Germline genetic variations in drug action pathways predict clinical outcomes in advanced lung cancer treated with platinum-based chemotherapy. Pharmacogenet Genomics, 2008. 18(11): p. 955-65.
84. Etzel, C.J., et al., Development and validation of a lung cancer risk prediction model for African-Americans. Cancer Prev Res (Phila), 2008. 1(4): p. 255-65.
85. 利德江, 應用兩階段分類法提升SVM法之分類轉確率. 國立成功大學工業與資訊管理研究所, 93年.
86. 陳士杰, 決策樹學習. 國立聯合大學資訊管理學系, 2005.
87. NCBI/dbSNP BUILD 133. Available from: http://www.ncbi.nlm.nih.gov/snp.
88. Ricci, Z., D.N. Cruz, and C. Ronco, Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria. Nat Rev Nephrol, 2011. 7(4): p. 201-8.
89. Marsh, D.J. and V.M. Howell, The use of denaturing high performance liquid chromatography (DHPLC) for mutation scanning of hereditary cancer genes. Methods Mol Biol, 2010. 653: p. 133-45.
90. Theophilus, B.D. and R. Rapley, PCR mutation detection protocols. Preface. Methods Mol Biol, 2011. 688: p. v.
91. Tagman SNP Genotyping Assays, in Applied Biosystems.
92. Sullivan, L.M., J.M. Massaro, and R.B. D'Agostino, Sr., Presentation of multivariate data for clinical use: The Framingham Study risk score functions. Stat Med, 2004. 23(10): p. 1631-60.
93. Akobeng, A.K., Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice. Acta Paediatr, 2007. 96(4): p. 487-91.
94. Chen, S., et al., Association of MDR1 and ERCC1 polymorphisms with response and toxicity to cisplatin-based chemotherapy in non-small-cell lung cancer patients. Int J Hyg Environ Health, 2010. 213(2): p. 140-5.
95. Lassnigg, A., et al., Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol, 2004. 15(6): p. 1597-605.
96. Planchard, D., et al., Differential expression of biomarkers in men and women. Semin Oncol, 2009. 36(6): p. 553-65.
97. Kiyohara, C. and Y. Ohno, Sex differences in lung cancer susceptibility: a review. Gend Med, 2010. 7(5): p. 381-401.
98. Samimi, G., et al., Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. Clin Cancer Res, 2003. 9(16 Pt 1): p. 5853-9.


論文全文使用權限
  • 不同意授權瀏覽/列印電子全文服務。


  • 若您有任何疑問,請與我們聯絡!
    臺北醫學大學 圖書館 簡莉婷
    E-mail:etds@tmu.edu.tw
    Tel:(02) 2736-1661 ext.2519
    Fax:(02) 2737-5446