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

Matthias Barral; Annemilaï Raballand; Anthony Dohan; Philippe Soyer; Marc Pocard; Philippe Bonnin

doi:10.1016/j.ultrasmedbio.2015.10.012

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

Ultrasound Med Biol. 2016 Feb;42(2):438-46. doi: 10.1016/j.ultrasmedbio.2015.10.012. Epub 2015 Nov 28.

Authors

Matthias Barral¹, Annemilaï Raballand², Anthony Dohan¹, Philippe Soyer³, Marc Pocard⁴, Philippe Bonnin⁵

Affiliations

¹ 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.
² Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Beaujon Hospital, INSERM U728, Clichy, France.
³ Service of Visceral and Vascular Radiology, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France.
⁴ 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.
⁵ 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.

PMID: 26626491
DOI: 10.1016/j.ultrasmedbio.2015.10.012

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.

Keywords: Anti-angiogenic drugs; Duplex Doppler ultrasound imaging; Hepatocellular carcinoma; Murine model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / administration & dosage*
Animals
Carcinoma, Hepatocellular / diagnostic imaging
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / physiopathology
Drug Evaluation, Preclinical
Liver Circulation / drug effects
Liver Neoplasms / diagnostic imaging
Liver Neoplasms / drug therapy*
Liver Neoplasms / physiopathology
Male
Mice
Mice, Transgenic
Neovascularization, Pathologic / complications
Neovascularization, Pathologic / diagnostic imaging
Neovascularization, Pathologic / drug therapy*
Reproducibility of Results
Sensitivity and Specificity
Treatment Outcome
Ultrasonography / methods*

Substances

Angiogenesis Inhibitors