PPARgamma and Agonists against Cancer: Rational Design of Complementation Treatments.

PPARgamma and Agonists against Cancer: Rational Design of Complementation Treatments.
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DOI:
10.1155/2008/945275
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发表时间:
2008
期刊:
影响因子:
2.9
通讯作者:
Volpert, Olga V.
Volpert, Olga V.
中科院分区:
医学3区
文献类型:
--
作者:
Veliceasa, Dorina;Schulze-Hoepfner, Frank Thilo;Volpert, Olga V.

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PPARγ是配体激活核受体超家族的成员:其配体作为胰岛素增敏剂,并且一些被批准用于治疗人类代谢紊乱。PPARγ对多种细胞类型(包括癌细胞)的存活和增殖具有多效性作用,目前是临床前癌症研究的重点。近十年的研究强调了PPARγ作为体外和体内血管生成的潜在调节剂的作用。这些观察结果为PPARγ图像作为潜在抗癌药物提供了额外的方面。目前,过氧化物酶体增殖物激活受体γ(PPARγ)被认为是治疗血管生成依赖性疾病(包括癌症和糖尿病血管并发症)的重要靶点。然而,一些研究确定了PPARγ及其配体的促血管生成和促肿瘤作用,指出需要进一步研究。下面,我们总结了目前对PPARγ调节机制和分子靶点的了解,并讨论了最大化PPARγ激动剂有益活性的方法。
PPARγ is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPARγ has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPARγ role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPARγ image as potential anticancer drug. Currently PPARγ is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPARγ and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPARγ regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPARγ agonists.
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