RESUMEN
BACKGROUND/AIMS: Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Based on former discoveries of good liver cell compatibility, safety and tumour-specific inhibition of hydroxyapatite nanoparticles (nHAP), this work tries to make nHAP serve as gene vector in the hepatoma-targeted trans-arterial embolization (TAE) gene therapy to elevate and synergize the therapeutic efficacy of TAE and target gene therapy. METHOD: Following dosage and ratio optimization, polypolex formed by surface modified nHAP and p53 expressing plasmid was applied in vitro for human hepatoma HePG2 cell, and then in vivo for rabbit hepatic VX2 tumour by injection of polypolex/lipodoil emulsion to the hepatic artery in a tumour-target manner. RESULTS: In vitro, the polypolex transfected only about 5% HepG2 cells, but can elevate the inhibition of its growth and apoptosis in a much more degree while keeping safe to the normal hepatocyte line, L02. In vivo, the emulsion, with better dispersion than the polypolex and more specific tumour-target than lipiodol, mediated specific 4% p53 expression and antitumoural nanoparticle retention in the target tumour site, also significantly reduced tumour growth and prolonged the animal survival times more than the lipiodol (P < 0.05). CONCLUSIONS: In all, this new treatment based on nHAP can enhance therapeutic effect of HCC safely both in vitro and in vivo.
Asunto(s)
Carcinoma Hepatocelular/terapia , Durapatita/administración & dosificación , Embolización Terapéutica , Terapia Genética/métodos , Neoplasias Hepáticas/terapia , Nanopartículas , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular , Aceite Etiodizado/administración & dosificación , Estudios de Factibilidad , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Transferencia de Gen , Células Hep G2 , Humanos , Inyecciones Intraarteriales , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Necrosis , Conejos , Factores de Tiempo , Transfección , Carga Tumoral , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: To provide an overview of recent studies on transarterial chemoembolization-related hepatic and biliary damage (TRHBD) in patients with malignant hepatic tumors (MHT) and to explore the reasons for TRHBD. METHODS: Literature on the treatments for MHT by TACE was sought in PubMed and the related information was summarized. RESULTS: TRHBD is found to occur in the hepatic parenchymal cells, biliary tree and blood-vascular system. The damage is mainly due to ischemia resulting from embolic materials such as gelatin sponge and lipiodol. In addition, clinicians' skill levels in non-superselective catheterization, the health condition of the patients, and the chemical agents used may also be related to the damage. Most of the deterioration can be reversed if the patients are diagnosed and treated properly and promptly. CONCLUSIONS: Understanding the mechanisms of TRHBD more comprehensively is helpful in developing effective methods for prevention and treatment.