Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma

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• 作者：Matthias Barral^&lowast ; ; ^&dagger ; ; Annemilaï ; Raballand^&Dagger ; ; Anthony Dohan^&lowast ; ; ^&dagger ; ; Philippe Soyer^&dagger ; ; Marc Pocard^&lowast ; ; ^§ ; ; Philippe Bonnin^&lowast ; ; ^¶ ; ; ^{philippe.bonnin@aphp.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hepatocellular carcinoma ; Murine model ; Duplex Doppler ultrasound imaging ; Anti-angiogenic drugs
• 刊名：Ultrasound in Medicine & Biology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：42
• 期：2
• 页码：438-446
• 全文大小：2422 K

文摘

Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC.