|本期目录/Table of Contents|

[1]黄 勇 综述,马勇杰 审校.二氢嘧啶脱氢酶基因在乳腺癌中的研究进展[J].天津医科大学学报,2018,24(01):83-86.
点击复制

二氢嘧啶脱氢酶基因在乳腺癌中的研究进展(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
24卷
期数:
2018年01期
页码:
83-86
栏目:
综述
出版日期:
2018-01-20

文章信息/Info

Title:
-
文章编号:
1006-8147(2018)01-0083-04
作者:
黄 勇 综述马勇杰 审校
(天津医科大学肿瘤医院,国家肿瘤临床医学研究中心,乳腺癌防治教育部重点实验室,天津市“肿瘤防治”重点实验室,天津市恶性肿瘤临床医学研究中心,天津300060)
Author(s):
-
关键词:
二氢嘧啶脱氢酶基因乳腺癌预后
Keywords:
-
分类号:
R737.9
DOI:
-
文献标志码:
A
摘要:
二氢嘧啶脱氢酶基因(DPYD)编码的二氢嘧啶脱氢酶(DPD)是人体嘧啶核苷酸分解的代谢酶,DPD也是氟尿嘧啶类药物体内代谢分解的起始和限速酶。本文论述了DPYD基因的生物学特征以及在乳腺癌患者中,DPYD基因与病理组织学改变、化疗后的毒副反应和患者预后之间的关系。在乳腺癌组织和癌旁组织中,DPYD基因的蛋白与mRNA表达水平存在明显差异。DPD蛋白与DPYD基因mRNA表达水平作为乳腺癌病人预后评估的意义存在较大争论,根据对DPYD基因的多态性与癌症患者预后的现有研究,认为DPYD基因的多态性可能作为乳腺癌患者预后评估的生物指标,指导乳腺癌患者化疗用药。开展针对乳腺癌病人DPYD多态性的探究,对乳腺癌患者个体化诊疗过程的推进具有重要意义。
Abstract:
-

参考文献/References:

[1] 陈万青, 郑荣寿, 张思维, 等. 2013年中国恶性肿瘤发病和死亡分析 [J]. 中国肿瘤, 2016, 25(1): 1

[2] Lu Z H, Zhang R, Diasio R B. Purification and characterization of dihydropyrimidine dehydrogenase from human liver [J]. J Biol Chem, 1992, 267(24): 17102

[3] Dobritzsch D, Schneider G, Schnackerz K D, et al. Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil [J]. EMBO J, 2001, 20(4): 650

[4] Ticha I, Kleiblova P, Fidlerova J, et al. Lack of large intragenic rearrangements in dihydropyrimidine dehydrogenase (DPYD) gene in fluoropyrimidine-treated patients with high-grade toxicity [J]. Cancer Chemother Pharmacol, 2009, 64(3): 615

[5] Furuhata T, Kawakami M, Okita K, et al. Plasma level of a 5-fluorouracil metabolite, fluoro-beta-alanine correlates with dihydropyrimidine dehydrogenase activity of peripheral blood mononuclear cells in 5-fluorouracil treated patients [J]. J Exp Clin Cancer Res, 2006, 25(1): 79

[6] Borro M, Botticelli A, Mazzuca F, et al. Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer [J]. Oncotarget, 2017, 8(8): 14050

[7] Rich T A, Shepard R C, Mosley S T. Four decades of continuing innovation with fluorouracil: current and future approaches to fluorouracil chemoradiation therapy [J]. J Clin Oncol, 2004, 22(11): 2214

[8] McLeod H L, Milne L H, Johnston S J. 5-Fluorouracil metabolizing enzymes [J]. Methods Mol Med, 1999, 28: 111

[9] Kono A, Hara Y, Sugata S, et al. Activation of 5’-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors [J]. Chem Pharm Bull (Tokyo), 1983, 31(1): 175

[10] Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue [J]. Eur J Cancer, 1998, 34(8): 1274

[11] Fukui Y, Oka T, Nagayama S, et al. Thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase mRNA and protein expression levels in solid tumors in large scale population analysis [J]. Int J Mol Med, 2008, 22(6): 709

[12] Horiguchi J, Yoshida T, Koibuchi Y, et al. DPD activity and immunohistochemical DPD expression in human breast cancer [J]. Oncol Rep, 2004, 11(1): 65

[13] Tamesa M, Yamamoto S, Maeda N, et al.Significance of pyrimidine nucleoside phosphorylase and dihydropyrimidine dehydrogenase levels to predict postoperative recurrence in primary breast cancer [J]. Gan To Kagaku Ryoho, 2008, 35(3): 431

[14] Gross E, Meul C, Raab S, et al. Somatic copy number changes in DPYD are associated with lower risk of recurrence in triple-negative breast cancers [J]. Br J Cancer, 2013, 109(9): 2347

[15] Yu Z, Sun J, Zhen J, et al. Thymidylate synthase predicts for clinical outcome in invasive breast cancer [J]. Histol Histopathol, 2005, 20(3): 871

[16] Kurebayashi J, Yamamoto Y, Udagawa K, et al. Establishment of enzyme-linked immunosorbent assays for thymidylate synthase and dihydropyriminide dehydrogenase in cancer tissues [J]. Oncol Rep, 2004, 11(5): 973

[17] Kosaka A, Mori K, Shikata A.Significance of tissue PyNPase, TS, and DPD activities in breast cancer[J]. Gan To Kagaku Ryoho, 2002, 29(8): 1395

[18] Anan K, Mitsuyama S, Tamae K, et al. Increased dihydropyrimidine dehydrogenase activity in breast cancer [J]. J Surg Oncol, 2003, 82(3): 174

[19] Ota D, Kusama M, Kaise H, et al. Evaluation of sensitivity to 5-FU on the basis of thymidylate synthase (TS)/dihydropyrimidine dehydrogenase (DPD) activity and chromosomal analysis in micro tissue specimens of breast cancer [J]. Breast Cancer, 2004, 11(4): 356

[20] Li H X, Zh S, Zhang Y H, et al. Expressions of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase in breast cancer and their correlations with prognosis [J]. Zhonghua Zhong Liu Za Zhi, 2004, 26(11): 669

[21] Aki F, Bando Y, Takahashi T, et al. A retrospective study on TS mRNA expression and prediction of the effects of adjuvant oral 5-fluorouracil in breast cancer [J]. Oncol Lett, 2010, 1(6): 981

[22] Tsunoda Y, Suzuki K, Tsunoda A, et al. Evaluation of 5-fluorouracil related genes in breast cancer to predict the effect of adjuvant therapy with oral fluorouracil derivatives [J]. Oncol Rep, 2010, 23(3): 771

[23] Lunenburg C A, Henricks L M, Guchelaar H J, et al. Prospective DPYD genotyping to reduce the risk of fluoropyrimidine-induced severe toxicity: Ready for prime time [J]. Eur J Cancer, 2016, 54: 40

[24] Yu Z, Yang Q, Sun J, et al. Dihydropyrimidine dehydrogenase activity correlates with fluorouracil sensitivity in breast cancer [J]. Exp Oncol, 2007, 29(3): 192

[25] Beuzeboc P, Pierga J Y, Lyonnet D S, et al.Severe 5-fluorouracil toxicity in a woman treated for breast cancer with concurrent osteogenesis imperfecta and dehydrogenase deficiency [J]. Bull Cancer, 1996, 83(4): 324

[26] Mokrim M, Aftimos P G, Errihani H, et al. Breast cancer, DPYD mutations and capecitabine-related ileitis: description of two cases and a review of the literature [J]. BMJ Case Rep, 2014, 2014

[27] Ostapowicz A, Dolegowska B. Review of methods for determination of dihydropyrimidine dehydrogenase and possible application in screening previous chemotheraphy with 5-fluorouracil [J]. Przegl Lek, 2012, 69(9): 694

[28] Harris B E, Song R, Soong S J, et al. Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion [J]. Cancer Res, 1990, 50(1): 197

[29] Sistonen J, Buchel B, Froehlich T K, et al. Predicting 5-fluorouracil toxicity: DPD genotype and 5,6-dihydrouracil:uracil ratio [J]. Pharmacogenomics, 2014, 15(13): 1653

[30] Bosch T M, Meijerman I, Beijnen J H, et al. Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer [J]. Clin Pharmacokinet, 2006, 45(3): 253

[31] Swen J J, Huizinga T W, Gelderblom H, et al. Translating pharmacogenomics: challenges on the road to the clinic [J]. PLoS Med, 2007, 4(8): e209

[32] Wei X, McLeod H L, McMurrough J, et al. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity [J]. J Clin Invest, 1996, 98(3): 610

[33] Milano G. Highlight on DPYD gene polymorphisms and treatment by capecitabine [J]. Scand J Clin Lab Invest Suppl, 2016, 76(245): S30

[34] Del Re M, Quaquarini E, Sottotetti F, et al. Uncommon dihydropyrimidine dehydrogenase mutations and toxicity by fluoropyrimidines: a lethal case with a new variant [J]. Pharmacogenomics, 2016, 17(1): 5

[35] Giorgio E, Caroti C, Mattioli F, et al. Severe fluoropyrimidine-related toxicity: clinical implications of DPYD analysis and UH2/U ratio evaluation [J]. Cancer Chemother Pharmacol, 2011, 68(5): 1355

[36] Honda J, Sasa M, Moriya T, et al. Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results [J]. J Med Invest, 2008, 55(1/2): 54

[37] Hakamada Y, Tsuchida A, Arima M, et al. Prognostic predictors in breast cancer patients with postoperative 5-fluorouracil-based chemotherapy [J]. Int J Mol Med, 2005, 16(2): 309

[38] Miyashita M, Yoshimura H, Hatta K, et al.Clinical significance of intratumoral TS levels and DPD activity in breast cancer [J]. Gan To Kagaku Ryoho, 2009, 36(3): 407

[39] Kakimoto M, Uetake H, Osanai T, et al. Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in breast cancer predicts 5-FU sensitivity by a histocultural drug sensitivity test [J]. Cancer Lett, 2005, 223(1): 103

[40] Zhao H Y, Huang H, Hu Z H, et al. Evaluations of biomarkers associated with sensitivity to 5-fluorouracil and taxanes for recurrent/advanced breast cancer patients treated with capecitabine-based first-line chemotherapy [J]. Anticancer Drugs, 2012, 23(5): 534

[41] Tsunoda Y, Suzuki K, Sakamoto M A, et al.Evaluation of 5-fluorouracil-related genes in breast cancer to predict the effect of adjuvant therapy with CMF [J]. Gan To Kagaku Ryoho, 2009, 36(1): 51

[42] Tecza K, Pamula-Pilat J, Lanuszewska J, et al. Genetic polymorphisms and response to 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients [J]. Oncotarget, 2016, 7(41): 66790

[43] Zeng H, Yu H, Lu L, et al. Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer [J]. Pancreas, 2011, 40(5): 657

[44] Deenen M J, Tol J, Burylo A M, et al. Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer [J]. Clin Cancer Res, 2011, 17(10): 3455

相似文献/References:

[1]朱悦,张诗武,张丹芳,等.TA2小鼠自发乳腺癌血清蛋白质组学研究[J].天津医科大学学报,2013,19(05):373.
[2]刘 营,孙保存,刘铁菊,等.AURKA蛋白激酶在三阴乳腺癌干细胞形成血管拟态中的实验研究[J].天津医科大学学报,2013,19(06):437.
 LIU Ying,SUN Bao-cun,LIU Tie-ju,et al.Experimental study of AURKA protein kinase in the formation of vascular mimicry in triple-negative breast cancer stem cells[J].Journal of Tianjin Medical University,2013,19(01):437.
[3]伦淑敏.HOXA5基因真核表达质粒的构建及在乳腺癌细胞中的功能研究[J].天津医科大学学报,2014,20(05):337.
 LUN Shu-min. Construction of HOXA5 eukaryotic expression plasmid of and its biological significance in breast cancer cells[J].Journal of Tianjin Medical University,2014,20(01):337.
[4]伦淑敏.肌细胞增强因子2A基因真核表达质粒的构建及对乳腺癌细胞MCF-7增殖能力的影响[J].天津医科大学学报,2014,20(06):429.
 LUN Shu-min.Construction of myocyte enhancer factor 2A eukaryotic expression plasmid and effects on cell proliferation in breast cancer cell line MCF7[J].Journal of Tianjin Medical University,2014,20(01):429.
[5]孙秀梅,张 飞,田 然,等.Nanog表达上调促进乳腺癌细胞MCF-7的增殖和侵袭[J].天津医科大学学报,2014,20(06):421.
 SUN Xiu-mei,ZHANG Fei,TIAN Ran,et al.Up-regulation of Nanog promotes cell proliferation and invasion in breast cancer cells MCF-7[J].Journal of Tianjin Medical University,2014,20(01):421.
[6]张 洁,张 飞,冀 为,等. SHP2不同突变体对乳腺癌细胞的迁移和侵袭能力的影响[J].天津医科大学学报,2015,21(02):93.
 ZHANG Jie,ZHANG Fei,JI Wei,et al. Effect of different SHP2 mutants on breast cancer cell migration and invasion[J].Journal of Tianjin Medical University,2015,21(01):93.
[7]蔡 隽. FOXQ1稳定表达乳腺癌细胞系的建立及鉴定[J].天津医科大学学报,2015,21(04):292.
 CAI Jun.Establishment and identification of cell lines with stable expression of FOXQ1 in MDA-MB-231-luc[J].Journal of Tianjin Medical University,2015,21(01):292.
[8]蔡 隽 综述,冯玉梅 审校.叉头框转录因子调控乳腺癌生物学特性的研究进展[J].天津医科大学学报,2015,21(05):455.
[9]任宗娜.沉默Notch4基因对乳腺癌细胞系MDA-MB-231增殖和迁移侵袭能力的影响[J].天津医科大学学报,2015,21(06):469.
 REN Zong-na.Inhibition effect of?silencing?? Notch4 gene on the proliferation and migration and invasion activity of? breast cancer cell line?MDA-MB-231[J].Journal of Tianjin Medical University,2015,21(01):469.
[10]周岩,宋伟杰,张飞,等.人附睾蛋白4在乳腺癌发生发展中的机制研究[J].天津医科大学学报,2015,21(06):466.
 ZHOU Yan,SONG Wei-jie,ZHANG Fei,et al.Mechanism of human epididymis protein 4 in development and progression of breast cancer[J].Journal of Tianjin Medical University,2015,21(01):466.

备注/Memo

备注/Memo:
基金项目 国家自然科学基金资助项目(81572851)

作者简介 黄勇(1991-),男,硕士在读,研究方向:乳腺癌的发生发展与化疗耐药机制;E-mail:huangyongxuexi@163.com。

更新日期/Last Update: 2018-01-23