The complexities of obesity and diabetes with the development and progression of pancreatic cancer.
The complexities of obesity and diabetes with the development and progression of pancreatic cancer.
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DOI：
10.1016/j.bbcan.2010.11.003
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发表时间：
2011-04
影响因子：
11.2
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Bao, Bin;Wang, Zhiwei;Li, Yiwei;Kong, Dejuan;Ali, Shadan;Banerjee, Sanjeev;Ahmad, Aamir;Sarkar, Fazlul H.
胰腺癌（PC）是最致命、预后最差的恶性疾病之一。在美国，它被列为癌症相关死亡的第四大原因。许多危险因素都与前列腺癌有关。有趣的是，大量流行病学研究表明，肥胖和糖尿病，特别是2型糖尿病，与PC风险增加呈正相关。同样，这些慢性疾病（肥胖、糖尿病和癌症）也是一个主要的公共卫生问题。在美国人口中，50%的人超重，30%的人医学上肥胖，10%的人患有糖尿病（DM）。因此，肥胖和糖尿病被认为是癌症的潜在危险因素；然而，本文的重点仅限于PC。虽然这些慢性疾病导致PC发展的机制尚不完全清楚，但胰岛素、胰岛素样生长因子-1 （IGF-1）及其受体（IGF-1R）信号通路的激活在胰岛素抵抗机制和随后诱导代偿性高胰岛素血症中的生物学重要性已被提出。因此，用降糖药物靶向胰岛素/IGF-1信号通路降低血胰岛素水平和逆转胰岛素抵抗可能是预防和/或治疗糖尿病的有效策略。大量研究表明，抗糖尿病药物如二甲双胍和噻唑烷二酮（TZD）类PPAR-γ激动剂可降低癌症风险，提示这些药物可能是治疗PC的有效抗肿瘤药物。在这篇综述文章中，我们将讨论二甲双胍和TZD抗糖尿病药物在PC背景下作为抗肿瘤药物的潜在作用，并进一步讨论microRNAs （miRNAs）在肥胖、糖尿病和PC发病机制中的复杂性和可能的作用。
Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin-resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC, and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes and PC.
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影响因子：
3.9
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
通讯作者：
Franceschi, C
影响因子：
16
作者：
Barak, Y;Nelson, MC;Evans, RM
通讯作者：
Evans, RM
影响因子：
0.7
作者：
Anisimov, VN;Egormin, PA;Semenchenko, AV
通讯作者：
Semenchenko, AV
影响因子：
3
作者：
Becker, Susen;Dossus, Laure;Kaaks, Rudolf
通讯作者：
Kaaks, Rudolf
影响因子：
--
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Arslan, Alan A.;Helzlsouer, Kathy J.;Kooperberg, Charles;Shu, Xiao-Ou;Steplowski, Emily;Bueno-de-Mesquita, H. Bas;Fuchs, Charles S.;Gross, Myron D.;Jacobs, Eric J.;LaCroix, Andrea Z.;Petersen, Gloria M.;Stolzenberg-Solomon, Rachael Z.;Zheng, Wei;Albanes, Demetrius;Amundadottir, Laufey;Bamlet, William R.;Barricarte, Aurelio;Bingham, Sheila A.;Boeing, Heiner;Boutron-Ruault, Marie-Christine;Buring, Julie E.;Chanock, Stephen J.;Clipp, Sandra;Gaziano, J. Michael;Giovannucci, Edward L.;Hankinson, Susan E.;Hartge, Patricia;Hoover, Robert N.;Hunter, David J.;Hutchinson, Amy;Jacobs, Kevin B.;Kraft, Peter;Lynch, Shannon M.;Manjer, Jonas;Manson, JoAnn E.;McTiernan, Anne;McWilliams, Robert R.;Mendelsohn, Julie B.;Michaud, Dominique S.;Palli, Domenico;Rohan, Thomas E.;Slimani, Nadia;Thomas, Gilles;Tjonneland, Anne;Tobias, Geoffrey S.;Trichopoulos, Ditnitrios;Virtamo, Jarmo;Wolpin, Brian M.;Yu, Kai;Zeleniuch-Jacquotte, Anne;Patel, Alpa V.
通讯作者：
Patel, Alpa V.