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1
Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis.二甲双胍摄入与2型糖尿病患者膀胱癌风险及肿瘤学结局的关联:一项系统评价和荟萃分析
Medicine (Baltimore). 2018 Jul;97(30):e11596. doi: 10.1097/MD.0000000000011596.
2
and targeting of bladder carcinoma with metformin in combination with cisplatin.以及二甲双胍联合顺铂对膀胱癌的靶向作用。
Oncol Lett. 2015 Aug;10(2):975-981. doi: 10.3892/ol.2015.3267. Epub 2015 May 26.
3
The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder.二甲双胍对接受根治性膀胱切除术治疗膀胱尿路上皮癌的糖尿病患者癌症特异性生存结局的影响。
Urol Oncol. 2015 Sep;33(9):386.e7-13. doi: 10.1016/j.urolonc.2015.05.024. Epub 2015 Jun 19.
4
Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors.二甲双胍依赖性抑制胰腺癌中雷帕霉素哺乳动物靶蛋白(mTOR)和Ras活性的机制:特异性蛋白(Sp)转录因子的作用
J Biol Chem. 2014 Oct 3;289(40):27692-701. doi: 10.1074/jbc.M114.592576. Epub 2014 Aug 20.
5
Incidence of bladder cancer in patients with type 2 diabetes treated with metformin or sulfonylureas.使用二甲双胍或磺脲类药物治疗的2型糖尿病患者膀胱癌的发病率。
Diabetes Care. 2014 Jul;37(7):1910-7. doi: 10.2337/dc13-1489. Epub 2014 Feb 4.
6
Metformin--mode of action and clinical implications for diabetes and cancer.二甲双胍——作用机制及在糖尿病和癌症中的临床意义。
Nat Rev Endocrinol. 2014 Mar;10(3):143-56. doi: 10.1038/nrendo.2013.256. Epub 2014 Jan 7.
7
The antidiabetic drug metformin inhibits the proliferation of bladder cancer cells in vitro and in vivo.抗糖尿病药物二甲双胍可抑制膀胱癌细胞的体外和体内增殖。
Int J Mol Sci. 2013 Dec 18;14(12):24603-18. doi: 10.3390/ijms141224603.
8
Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle-invasive bladder cancer.糖尿病和二甲双胍的使用与非肌肉浸润性膀胱癌患者的肿瘤学结局的关联。
BJU Int. 2013 Dec;112(8):1105-12. doi: 10.1111/bju.12448.
9
Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis.噻唑烷二酮类药物的使用与 2 型糖尿病患者膀胱癌风险的关系:一项荟萃分析。
CMAJ. 2012 Sep 4;184(12):E675-83. doi: 10.1503/cmaj.112102. Epub 2012 Jul 3.
10
Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro.二甲双胍和 mTOR 抑制剂依维莫司(RAD001)在体外增强乳腺癌细胞对化疗药物的细胞毒性作用。
Anticancer Res. 2012 May;32(5):1627-37.

超越糖尿病:二甲双胍在非肌肉浸润性膀胱癌中的作用。

Beyond diabetes mellitus: role of metformin in non-muscle-invasive bladder cancer.

机构信息

Department of Urology, National University Hospital, Singapore.

Department of Urology, National University of Singapore, Singapore.

出版信息

Singapore Med J. 2022 Apr;63(4):209-213. doi: 10.11622/smedj.2020121. Epub 2020 Aug 17.

DOI:10.11622/smedj.2020121
PMID:32798360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9251265/
Abstract

INTRODUCTION

Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes.

METHODS

Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS).

RESULTS

At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression.

CONCLUSION

Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.

摘要

简介

二甲双胍的使用与肺癌、乳腺癌和前列腺癌患者的生存率提高有关,并且在体外研究中已显示二甲双胍可抑制癌细胞生长和增殖。鉴于缺乏关于膀胱癌患者使用二甲双胍的临床数据,我们旨在评估二甲双胍在他们的肿瘤学结局中的作用。

方法

从一项前瞻性维持的 122 名接受膀胱内卡介苗(BCG)治疗的非肌肉浸润性膀胱癌患者的药物使用数据库中收集并分析了数据,这些患者是在一项随机、双盲、对照临床试验中招募的。使用 Kaplan-Meier 曲线评估总生存期(OS)和疾病特异性生存期(DSS)。

结果

在中位数为 102 个月(范围 3-357)的随访期间,53 名(43.4%)患者出现疾病复发,21 名(17.2%)患者出现疾病进展。有和没有糖尿病的患者之间的死亡率没有显著差异。无糖尿病的患者、服用二甲双胍的糖尿病患者和患有糖尿病但未服用二甲双胍的患者之间的 OS 存在显著差异(p = 0.033);服用二甲双胍的糖尿病患者预后最佳。二甲双胍的使用与显著较低的 DSS 相关(p = 0.042)。其他口服降糖药、胰岛素或他汀类药物与疾病复发或进展无关。

结论

在接受膀胱内 BCG 治疗的非肌肉浸润性膀胱癌患者中,二甲双胍的使用与改善肿瘤学结局相关。需要进行具有更大患者群体的前瞻性研究,以验证二甲双胍作为膀胱癌潜在治疗方法的作用。