RESUMO

Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin-like growth factor-1 (IGF-1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models. In this study, we evaluated whether intracisternal (IC) route for IGF-1 gene therapy may abrogate or at least reduce the structural and behavioral damages induced by the intraparenchymal injection of kainic acid (KA) into the rat spinal cord. Experimental (Rad-IGF-1) and control (Rad-DsRed-KA) rats were evaluated using a battery of motor and sensory tests before the injection of the recombinant adenovector (day -3), before KA injection (day 0) and at every post-injection (pi) time point (days 1, 2, 3 and 7 pi). Histopathological changes and neuronal and glial counting were assessed. Pretreatment using IC delivery of RAd-IGF-1 improved animal's general condition and motor and sensory functions as compared to Rad-DsRed-KA-injected rats. Besides, IC Rad-IGF-1 therapy abrogated later spinal cord damage and reduced the glial response induced by KA as observed in Rad-DsRed-KA rats. We conclude that the IC route for delivering RAd-IGF-1 prevents KA-induced excitotoxicity in the spinal cord.

Assuntos

Ácido Caínico , Fármacos Neuroprotetores , Animais , Terapia Genética , Fator de Crescimento Insulin-Like I/genética , Ácido Caínico/toxicidade , Ratos , Ratos Sprague-Dawley , Medula Espinal

RESUMO

BACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer death. Single or multiple mutations in genes related to growth control, apoptosis, invasion and metastasis have been determined; so a better understanding of the molecular genetic basis of malignant transformation, tumor progression and host interaction has led to significant progress in the development of new therapeutic agents. The ability of adenovirus vectors to deliver and express genes at high yields in HCC treatment has been demonstrated and well documented over the last few years. OBJECTIVE: To overview and provide an update of what has been accomplished in the field of adenoviral gene therapy and its application in hepatocellular carcinoma treatment. METHODS: Original articles were searched using Pubmed and other medical databases to get the most representative and actual information to establish the current state of the investigation of Ad vectors in HCC. RESULTS: Good results have been accomplished in preclinical models using new Ad vectors and especially AAV vectors, it is important to motivate further clinical trials to corroborate all the experience obtained. CONCLUSIONS: Ad and AAV must be considered as an opportunity to improve the quality of life and survival of HCC patients.