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Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Protein & Cell 2010年第7期1卷 638-655页

作者： Zhi Huang Lin Cheng Olga A.Guryanova Qiulian Wu Shideng Bao Department of Stem Cell Biology and Regenerative Medicine Lerner Research InstituteCleveland ClinicClevelandOH 44195USA

Glioblastomas(GBMs)are highly lethal primary brain *** current therapeutic advances in other solid cancers,the treatment of these malignant gliomas remains essentially *** are extremely resistant to conventional radiation and *** and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells(GSCs)promotes therapeutic *** also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth,which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive ***,stem cell-like cancer cells(cancer stem cells)have been shown to promote *** GBMs rarely metastasize beyond the central nervous system,these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection,and GSCs display an aggressive invasive *** studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM *** studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells,but also display critical distinctions that provide important clues into useful therapeutic *** this review,we summarize the current understanding and advances in glioma stem cell research,and discuss potential targeting strategies for future development of anti-GSC therapies.

关键词： cancer stem cell glioblastoma therapeutic resistance molecular targeting tumor angiogenesis hypoxia response stem cell niche

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Effects of hypoxia-inducible factor 1 on ischemic cerebrovascular disease

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Neural Regeneration Research 2008年第10期3卷 1156-1160页

作者： Yongjie Luo Xiaoping Wang Hongbin Sun Department of Neurology Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇s Hospital Chengdu 610072 Sichuan Province China

hypoxia-inducible factor 1, a nuclear transcription factor, is induced by hypoxia. hypoxia-inducible factor 1, a heterodimeric DNA-binding protein, is composed of hypoxia-inducible factor 1α and hypoxia-inducible factor 1βsubunits, which are family members of the basic helix-loop-helix-PER, ARNT, SIM （PAS） protein. O2 concentration regulates hypoxia-inducible factor 1 activity via this subunit. hypoxia-inducible factor 1α plays a major role in response to hypoxia and transcriptional activation, as well as in the target gene specificity of the DNA enhancer. hypoxia-inducible factor 1β cannot be induced by hypoxia. This effect may be due to hypoxia-inducible factor 1 stability and activated conformation due to dimerization. Previous studies have shown that hypoxia-inducible factor 1 mRNA expression increases in the penumbra following ischemia/hypoxia. hypoxia-inducible factor 1 plays an important role in brain tissue injury after ischemia by affecting a series of target genes, elevating tolerance to hypoxia, and ensuring survival of neural cells. This article summarizes the structure, function, expression, regulatory mechanisms, biological effects, and significance of hypoxia-inducible factor 1 in patients with ischemic cerebrovascular disease. As a transcriptional activator, hypoxia- inducible factor 1 plays a key role in hypoxic responses by stabilizing the internal environment. It also has been shown to regulate the expression of several genes. The regulatory effects of hypoxia-inducible factor 1 in patients with ischemic cerebrovascular disease have been described. The present review re-examined the concept of brain protection at the level of gene regulation.

关键词： hypoxia-inducible factor 1 hypoxia response ischemic cerebrovascular disease target gene regulation

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