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细胞程序性坏死:胶质母细胞瘤的一种新的治疗靶点。

Necroptosis: a novel therapeutic target for glioblastoma.

机构信息

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, China.

出版信息

Med Hypotheses. 2011 Mar;76(3):350-2. doi: 10.1016/j.mehy.2010.10.037. Epub 2010 Nov 13.

Abstract

Glioblastoma or glioblastoma multiforme (GBM) is the most encountered and malignant form of brain tumors in clinical practice. In spite of optimal and early treatment, the life expectancy of patients with GBM remains poor. It is believed that dysfunction of apoptosis underlies GBM tumorigenesis, proliferation and resistance to chemotherapy and radiotherapy. Although GBM is defective in apoptotic process, pathologic and radiologic observations almost always reveal obvious necrosis foci within GBM. Necrosis seems to be related with GBM proliferation, angiogenesis and invasion. However, tumor cell necrosis induced by various therapies has a potential therapeutic value. Just recently, necrotic cell death is considered as a regulated and controlled process, like apoptosis, termed necroptosis or programmed necrosis. Induction of apoptosis has not made any significant achievements in the treatment of GBM mainly because the tumor cells are apoptosis-resistant. We may achieve a better result by modulating the necroptosis of GBM thus circumvent the apoptosis resistance. Albeit specific molecular pathways involved in GBM necroptosis is not clear and much more studies are needed to confirm the effects of therapy-induced necroptosis on GBM, it provides us with a new direction in the treatment of GBM.

摘要

胶质母细胞瘤或多形性胶质母细胞瘤(GBM)是临床实践中最常见和最恶性的脑肿瘤形式。尽管进行了最佳和早期治疗,GBM 患者的预期寿命仍然很差。据信,细胞凋亡功能障碍是 GBM 肿瘤发生、增殖和对化疗和放疗耐药的基础。尽管 GBM 在凋亡过程中存在缺陷,但病理和影像学观察几乎总是在 GBM 内发现明显的坏死灶。坏死似乎与 GBM 的增殖、血管生成和侵袭有关。然而,各种治疗方法诱导的肿瘤细胞坏死具有潜在的治疗价值。就在最近,坏死细胞死亡被认为是一种像凋亡一样受调控和控制的过程,称为坏死性凋亡或程序性坏死。诱导凋亡在 GBM 的治疗中并没有取得任何显著的成就,主要是因为肿瘤细胞对凋亡有抗性。我们可以通过调节 GBM 的坏死性凋亡来获得更好的效果,从而避免凋亡抗性。尽管涉及 GBM 坏死性凋亡的特定分子途径尚不清楚,需要更多的研究来证实治疗诱导的坏死性凋亡对 GBM 的影响,但它为 GBM 的治疗提供了一个新的方向。

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