Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.
Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.
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重组人内皮抑素使异种移植人鼻咽癌模型中的肿瘤血管正常化并增强放射反应
DOI：
10.1371/journal.pone.0034646
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Peng F;Xu Z;Wang J;Chen Y;Li Q;Zuo Y;Chen J;Hu X;Zhou Q;Wang Y;Ma H;Bao Y;Chen M
低氧的肿瘤细胞会降低放射的疗效。抗血管生成治疗可能会暂时使肿瘤血管“正常化”，使其更有效地输送氧气。本研究旨在探讨重组人内皮抑素(Endostar)能否在小鼠鼻咽癌(NPC)中创造一个“血管正常化窗口”，以缓解缺氧和增强放射治疗的抑制作用。在携带CNE-2和5-8F人鼻咽癌移植瘤的小鼠中，检测到肿瘤血管形态和低氧肿瘤细胞分数对Endostar的反应的暂时性变化。测试不同的治疗方案，以评估Endostar对放射治疗效果的影响。通过免疫组织化学染色确定与血管生成相关的几个重要因素。在Endostar治疗期间，肿瘤血管减少，而与内皮细胞相关的基底膜和周细胞覆盖率增加，这支持了血管正常化的想法。治疗后低氧肿瘤细胞百分率也有所下降。与其他治疗方案相比，Endostar对肿瘤生理的瞬时调节改善了放射治疗的效果。血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP2)、MMP9、MMP14表达减少，色素上皮衍生因子(PEDF)表达增加。Endostar使肿瘤血管正常化，从而缓解了鼻咽癌的缺氧，并显著增敏了放疗的抗肿瘤作用。本研究结果为Endostar与鼻咽癌放射治疗联合应用提供了重要的实验依据。
Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently “normalize” the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar) can create a “vascular normalization window” to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC) in mice. Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5–8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF) increased. Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.
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表皮生长因子受体抑制通过血管正常化调节微环境，从而提高化疗和放疗疗效。
影响因子：
3.7
作者：
Cerniglia, George J.;Pore, Nabendu;Tsai, Jeff H.;Schultz, Susan;Mick, Rosemarie;Choe, Regine;Xing, Xiaoman;Durduran, Turgut;Yodh, Arjun G.;Evans, Sydney M.;Koch, Cameron J.;Hahn, Stephen M.;Quon, Harry;Sehgal, Chandra M.;Lee, William M. F.;Maity, Amit
通讯作者：
Maity, Amit
影响因子：
4.8
作者：
Gao, GQ;Li, Y;Ma, JX
通讯作者：
Ma, JX
影响因子：
3
作者：
Hardee, Matthew E.;Eapen, Rose J.;Dewhirst, Mark W.
通讯作者：
Dewhirst, Mark W.
影响因子：
8.4
作者：
Lee, Anne W. M.;Tung, Stewart Y.;Lau, W. H.
通讯作者：
Lau, W. H.
DOI：
10.1016/j.bbrc.2007.06.155
发表时间：
2007-09-14
影响因子：
3.1
作者：
Ling, Yun;Yang, Yong;Guo, Qing-Long
通讯作者：
Guo, Qing-Long