title: Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma.
abstract: 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.
authors.affiliation: Paris-Diderot University, Sorbonne Paris Cite, Lariboisiere Hospital, INSERM U965, Paris, France; Service of Visceral and Vascular Radiology, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barral
authors.affiliation: Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Beaujon Hospital, INSERM U728, Clichy, France.
authors.forename: Annemilaï
authors.initials: A
authors.lastname: Raballand
authors.affiliation: Paris-Diderot University, Sorbonne Paris Cite, Lariboisiere Hospital, INSERM U965, Paris, France; Service of Visceral and Vascular Radiology, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Dohan
authors.affiliation: Service of Visceral and Vascular Radiology, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Soyer
authors.affiliation: Paris-Diderot University, Sorbonne Paris Cite, Lariboisiere Hospital, INSERM U965, Paris, France; Service of Digestive and Cancer Surgery, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.affiliation: Paris-Diderot University, Sorbonne Paris Cite, Lariboisiere Hospital, INSERM U965, Paris, France; Service of Clinical Physiology- Functional Investigations, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France. Electronic address: philippe.bonnin@aphp.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D008102:Liver Circulation / Q000187:drug effects; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods*
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Anti-angiogenic drugs; Duplex Doppler ultrasound imaging; Hepatocellular carcinoma; Murine model