Avastin enhances photodynamic therapy treatment of Kaposi's sarcoma in a mouse tumor model
Avastin enhances photodynamic therapy treatment of Kaposi's sarcoma in a mouse tumor model
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DOI：
10.1615/jenvironpatholtoxicoloncol.v25.i1-2.160
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
Gomer, CJ
中科院分区：
文献类型：
--
作者：
Ferrario, A;Gomer, CJ
当前研究的目的是确定抗血管生成药物阿瓦斯汀是否会提高卡波西肉瘤 (KS) 异种移植模型中光动力疗法 (PDT) 的有效性。移植到裸鼠体内的人 KS-Imm 肿瘤采用 Photofrin 介导的 PDT 进行治疗。记录了促血管生成分子的表达参数，并确定了 PDT 与 VEGF 抑制剂阿瓦斯汀联合的杀肿瘤效果。 PDT 诱导治疗的 KS 肿瘤组织中 HIF-1 α、VEGF、PGE(2)、TNF-α 和 IL-1 β 的表达增加。在治疗的肿瘤内检测到源自KS细胞的人VEGF的显着过度表达以及源自宿主细胞的小鼠VEGF的较小程度的过度表达。与单独治疗相比，PDT 与阿瓦斯汀相结合可显着提高治疗 KS 肿瘤的长期反应性。这些结果首次证明阿瓦斯汀可以提高PDT治疗效果，并表明VEGF抑制剂可能改善PDT的临床疗效。
The goal of the current study was to determine if the antiangiogenic drug Avastin would improve the effectiveness of Photodynamic Therapy (PDT) in a xenograft model of Kaposi's sarcoma (KS). Human KS-Imm tumors transplanted in nude mice were treated with Photofrin-mediated PDT. Expression parameters of pro-angiogenic molecules were documented and the tumoricidal effectiveness of PDT combined with the VEGF inhibitor Avastin was determined. PDT induced increased expression of HIF-1 alpha, VEGF, PGE(2), TNF-alpha, and IL-1 beta within treated KS tumor tissue. Significant overexpression of KS cell derived human VEGF and to a lesser extent overexpression of host cell derived mouse VEGF were detected within treated tumors. Combining PDT with Avastin resulted in a significant increase in the long-term responsiveness of treated KS tumors when compared to individual treatments. These results demonstrate for the first time that Avastin can improve PDT treatment effectiveness and suggest that VEGF inhibitors may ameliorate the clinical efficacy of PDT.