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通过 KSHV 对血管内皮细胞的操纵:对血管生成和异常血管分化的影响。

Manipulation of endothelial cells by KSHV: implications for angiogenesis and aberrant vascular differentiation.

机构信息

Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 University of Helsinki, Finland; Foundation for the Finnish Cancer Institute, Helsinki, Finland; Section of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.

Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

出版信息

Semin Cancer Biol. 2014 Jun;26:69-77. doi: 10.1016/j.semcancer.2014.01.008. Epub 2014 Jan 28.

Abstract

Kaposi sarcoma (KS), a viral cancer associated to Kaposi sarcoma herpesvirus (KSHV) infection, is currently the most common tumor in men in sub-Saharan Africa. KS is an angiogenic tumor and characterized by the presence of aberrant vascular structures in the lesion. Although our understanding of how KSHV causes the aberrant differentiation of endothelial cells and the typical vascular abnormalities in KS tumors is far from complete, the experimental evidence reviewed here provides a comprehensive description of the role of KSHV in the pathogenesis of this unusual tumor. In contrast to other tumor viruses, whose interference with cellular processes relating to cell cycle, apoptosis and DNA damage may be at the heart of their oncogenic properties, KSHV may cause KS primarily by its ability to engage with the differentiation and function of endothelial cells. Although the intracellular pathways engaged by KSHV in the endothelial cells are being explored as drug targets, a better understanding of the impact of KSHV on endothelial cell differentiation and vasculogenesis is needed before the encouraging findings can form the basis for new targeted therapeutic approaches to KS.

摘要

卡波西肉瘤(KS)是一种与卡波西肉瘤疱疹病毒(KSHV)感染相关的病毒性癌症,目前是撒哈拉以南非洲地区男性中最常见的肿瘤。KS 是一种血管生成性肿瘤,其病变中存在异常的血管结构。尽管我们对 KSHV 如何导致内皮细胞的异常分化以及 KS 肿瘤中典型的血管异常的理解还远不完整,但这里综述的实验证据提供了对 KSHV 在这种不寻常肿瘤发病机制中的作用的全面描述。与其他肿瘤病毒不同,其对与细胞周期、细胞凋亡和 DNA 损伤相关的细胞过程的干扰可能是其致癌特性的核心,KSHV 可能主要通过其与内皮细胞的分化和功能的相互作用而导致 KS。尽管正在探索 KSHV 在内皮细胞中涉及的细胞内途径作为药物靶点,但在令人鼓舞的发现能够为针对 KS 的新靶向治疗方法奠定基础之前,需要更好地了解 KSHV 对内皮细胞分化和血管生成的影响。

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