...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Metformin and cancer: Doses, mechanisms and the dandelion and hormetic phenomena.
【24h】

Metformin and cancer: Doses, mechanisms and the dandelion and hormetic phenomena.

机译：二甲双胍和癌症：剂量，机制以及蒲公英和蜂鸣现象。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In the early 1970s, Professor Vladimir Dilman originally developed the idea that antidiabetic biguanides may be promising as geroprotectors and anticancer drugs ("metabolic rehabilitation"). In the early 2000s, Anisimov's experiments revealed that chronic treatment of female transgenic HER2-eu mice with metformin significantly reduced the incidence and size of mammary adenocarcinomas and increased the mean latency of the tumors. Epidemiological studies have confirmed that metformin, but not other anti-diabetic drugs, significantly reduces cancer incidence and improves cancer patients' survival in type 2 diabetics. At present, pioneer work by Dilman & Anisimov at the Petrov Institute of Oncology (St. Petersburg, Russia) is rapidly evolving due to ever-growing preclinical studies using human tumor-derived cultured cancer cells and animal models. We herein critically review how the antidiabetic drug metformin is getting reset to metabolically fight cancer. Our current perception is that metformin may constitute a novel "hybrid anti-cancer pill" physically combining both the long-lasting effects of antibodies-by persistently lowering levels of blood insulin and glucose-and the immediate potency of a cancer cell-targeting molecular agent-by suppressing the pivotal AMPK/mTOR/S6K1 axis and several protein kinases at once, including tyrosine kinase receptors such as HER1 and HER2-. In this scenario, we discuss the relevance of metformin doses in pre-clinical models regarding metformin's mechanisms of action in clinical settings. We examine recent landmark studies demonstrating metformin's ability to specifically target the cancer-initiating stem cells from which tumor cells develop, thereby preventing cancer relapse when used in combination with cytotoxic chemotherapy (dandelion hypothesis). We present the notion that, by acting as an efficient caloric restriction mimetic, metformin enhanced intrinsic capacity of mitotically competent cells to self-maintenance and repair (hormesis) might trigger counterintuitive detrimental effects. Ongoing chemopreventive, neoadjuvant and adjuvant trials should definitely establish whether metformin's ability to kill the "dandelion root" beneath the "cancer soil" likely exceeds metformin-related dangers of hormesis.
机译：在1970年代初期，弗拉基米尔·迪尔曼（Vladimir Dilman）教授最初提出了这样的想法，即抗糖尿病双胍类药物有望成为抗炎药和抗癌药（“代谢修复”）。在2000年代初期，Anisimov的实验表明，用二甲双胍长期治疗雌性转基因HER2- / neu雌性小鼠，可显着降低乳腺腺癌的发病率和大小，并增加肿瘤的平均潜伏期。流行病学研究证实，二甲双胍可显着降低癌症的发生率，并提高癌症患者在2型糖尿病患者中的生存率，而其他抗糖尿病药物则不能。目前，由于使用人类肿瘤衍生的培养的癌细胞和动物模型进行的临床前研究不断增长，Dilman＆Anisimov在彼得罗夫肿瘤研究所（俄罗斯圣彼得堡）的工作正在迅速发展。我们在此严格审查抗糖尿病药物二甲双胍如何重置以代谢对抗癌症。我们目前的看法是，二甲双胍可能构成一种新型的“混合型抗癌药”，通过持续降低血液胰岛素和葡萄糖水平，并结合了抗体的长效作用以及靶向癌细胞的分子试剂的即时功效-通过同时抑制关键的AMPK / mTOR / S6K1轴和几种蛋白激酶，包括酪氨酸激酶受体（如HER1和HER2-）。在这种情况下，我们将在临床前模型中讨论二甲双胍剂量与临床环境中二甲双胍作用机制的相关性。我们检查了近期具有里程碑意义的研究，这些研究证明了二甲双胍能够特异性靶向肿瘤细胞从中引发癌症的干细胞，从而在与细胞毒性化学疗法（蒲公英假说）结合使用时可预防癌症复发。我们提出了这样的观念，即通过作为有效的热量限制模拟物，二甲双胍增强有丝分裂感受态细胞自我维持和修复（内吞）的内在能力，可能会引发违反直觉的有害影响。正在进行的化学预防，新辅助和辅助试验肯定应确定二甲双胍杀死“癌性土壤”下的“蒲公英根”的能力是否可能超过与二甲双胍有关的毒副作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号