Imaging angiogenesis and the microenvironment.
Imaging angiogenesis and the microenvironment.
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DOI：
10.1111/j.1600-0463.2008.01148.x
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Jain RK
中科院分区：
文献类型：
--
作者：
Fukumura D;Jain RK
活体显微镜为肿瘤病理生理学提供了前所未有的见解，包括血管生成和微环境。肿瘤血管显示异常的组织、结构和功能。肿瘤血管渗漏，血流不均匀，经常受损。血管通透性过高和肿瘤内功能性淋巴管的缺乏导致实体瘤间质液压力升高。这些异常形成了向肿瘤递送治疗剂的生理屏障，并且还导致了以缺氧和酸中毒为特征的不利微环境，这阻碍了抗肿瘤治疗如放射疗法和化学疗法的有效性。此外，宿主-肿瘤相互作用调节促血管生成因子和抗血管生成因子的表达，导致肿瘤的病理生理学特征。另一方面，在生理环境中，血管生成血管变得成熟并形成持久的功能单元。恢复肿瘤中促血管生成因子和抗血管生成因子的平衡可以使肿瘤血管系统“正常化”，从而改善其功能。在血管正常化过程中给予细胞毒治疗将增强其疗效。
Intravital microscopy has provided unprecedented insights into tumor pathophysiology, including angiogenesis and the microenvironment. Tumor vasculature shows an abnormal organization, structure, and function. Tumor vessels are leaky, blood flow is heterogeneous and often compromised. Vascular hyperpermeability and the lack of functional lymphatic vessels inside tumors causes elevation of interstitial fluid pressure in solid tumors. These abnormalities form physiological barriers to the delivery of therapeutic agents to tumors and also lead to a hostile microenvironment characterized by hypoxia and acidosis, which hinders the effectiveness of anti-tumor treatments such as radiation therapy and chemotherapy. In addition, host-tumor interactions regulate expression of pro- and anti-angiogenic factors, resulting in pathophysiological characteristics of the tumor. On the other hand, in a physiological setting, angiogenic vessels become mature and form long-lasting functional units. Restoring the balance of pro- and anti-angiogenic factors in tumors may “normalize” tumor vasculature and thus improve its function. Administration of cytotoxic therapy during the vascular normalization would enhance its efficacy.
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