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- W2283142438 abstract "Increased pericyte coverage has been suggested to be one of the resistant mechanisms of anti-angiogenic treatment (AAT), but targeting pericytes disrupts tumor vascular normalization and abolishes the benefit of oxygenation for the combination of irradiation (IR) with AAT. This raises the question of whether pericyte inhibition should be added to the combination of AAT and IR. We and others have shown that Endostar (Endo), a humanized endostatin, induces a normalization window starting from D5, characterized by decreased tumor hypoxia and increased pericyte coverage of vessels. In this study, we tried to utilize the reduced hypoxia in vascular normalization window to radiosensitize tumor and attempted to test whether inhibiting pericytes after the window may result in optimal anti-tumor effect. Subcutaneous Lewis lung carcinoma was used as the tumor model. Pericyte inhibition was achieved by administering CP673451 (CP) at a dose of 20mg/kg, a platelet-derived growth factor receptor (PDGFR) inhibitor. Endo was given daily for 10 days. 12Gy/1f IR was administered on D5 post-endostar initiation. CP was given from D6 to D10 in order not to interfere with the hypoxia alleviation by Endo when IR was given. We found that percentage of pericyte-covered endothelial cells was the lowest in IR+Endo+CP group compared to IR alone and IR+Endo. IR+Endo+CP significantly reduced tumor growth rate compared to the other two groups. However, the local growth retardation was not translated to mice survival benefits, without even any trend could be suggested. We next found that trimodality treatment resulted in significantly more metastasis in mice lungs. This might be due to increased tumor hypoxia in RT+Endo+CP group, which was found to be the highest among the three. Thus, we hereby conclude that adding pericytes inhibition to the combination of IR and AAT even without interfering vascular normalization when IR is administered confers benefit to local tumor control but not to mice survival, due to increased hypoxia and distant metastasis. Citation Format: Lei Deng, Jiazhuo He, Jianxin Xue, Jie Lan, Lin Zhou, Yongmei Liu, You Lu. Adding pericyte inhibition to combined anti-angiogenesis and irradiation slows tumor growth but increases metastasis in mice model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3322. doi:10.1158/1538-7445.AM2015-3322" @default.
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- W2283142438 date "2015-08-01" @default.
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- W2283142438 title "Abstract 3322: Adding pericyte inhibition to combined anti-angiogenesis and irradiation slows tumor growth but increases metastasis in mice model" @default.
- W2283142438 doi "https://doi.org/10.1158/1538-7445.am2015-3322" @default.
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