INVESTIGADORES
GARCIA Mariana Gabriela
congresos y reuniones científicas
Título:
Combination of 4-methylumbelliferone and adenoviral gene transfer of interleukin-12 reduced the expression of cancer stem cells markers, and showd a potent antitumor effec in an experimental hepatocellular model with fibrosis
Autor/es:
RODRÍGUEZ MM ; MALVICINI M; FIORE E; BUSTILLO SG; PICCIONI F; PEIXOTO E; ATORRASAGASTI C; GARCIA M; ALANIZ L; MAZZOLINI G
Reunión:
Congreso; Reunión anual de la EASL (European Association for the Study of the Liver); 2016
Resumen:
Background and Aims: The incidence of hepatocellular carcinoma (HCC) has grown significantly in the last decade. Curative treatments for HCC can only be applied in less than 30% of cases. Therefore, new therapeutic options are needed. We have demonstrated that HCC overexpressed an essential ECM component, hyaluronic acid (HA) and HA synthesis inhibition using a selective inhibitor 4-methylumbelliferone (4Mu) demonstrated anti-fibrotic and antitumor activity in a murine model of HCC associated with liver fibrosis. The aim of this work was to study the use of 4Mu in combination with gene therapy of interleukin 12 mediated by an adenovirus (AdIL-12) in a murine model of HCC associated withadvanced fibrosis induced by thioacetamide (TAA).Methods: After 4 weeks of TAA administration (200 mg/kg) male C3H mice received intrahepatic injection of 1,25 × 10e5 Hepa 129 cells (day 0). On day 5 mice were distributed in experimental groups (n = 8/group): i) saline (control); ii) 4Mu 200 mg/Kg, drinking water (day 5); iii) AdIL-12 1 × 10e9 DICT50/mL, i.v (day 9); iv) 4Mu + Adβ-gal 1 × 10e9 DICT50/mL, i.v (day 9); v) 4Mu + AdIL-12 1 × 10e9 DICT50/mL, i.v. Tumor volume was measured and survival studies were carried out.Tumor samples were taken to determine levels of CSCs.Results: Administration of 4 Mu or AdIL-12 alone induced a slightly reduction of liver tumor volume respect to saline group. Interestingly, combined treatment induced a significant reduction of HCC size (p