| Journal: | Ciencia UANL |
| Database: | PERIÓDICA |
| System number: | 000344958 |
| ISSN: | 1405-9177 |
| Authors: | Delgado Enciso, Iván1 Cervantes García, Daniel2 Ortiz López, Rocío2 Barrera Saldaña, Hugo A2 Rojas Martínez, Augusto1 |
| Institutions: | 1Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey, Nuevo León. México 2Universidad de Colima, Facultad de Medicina, Manzanillo, Colima. México |
| Year: | 2008 |
| Season: | Oct-Dic |
| Volumen: | 11 |
| Number: | 4 |
| Pages: | 337-351 |
| Country: | México |
| Language: | Español |
| Document type: | Artículo |
| Approach: | Experimental, analítico |
| Spanish abstract | Diversas neoplasias epiteliales están asociadas a papilomavirus humanos (PVH) de alto riesgo, como los cánceres de cérvix, ano-rectal, cabeza y cuello, etc. Los vectores adenovirales oncolíticos (VAOs) han surgido como herramientas antineoplásicas prometedoras con efectos confinados a las células tumorales. Se construyeron una serie de VAOs controlados por la principal región promotora (URR) de la variante asiáticoamericana del PVH-16, los cuales contienen mutaciones en la región adenoviral E1A (mutaciones dl1015 y/o D24). Los vectores se probaron in vitro e in vivo para evaluar su replicación, citotoxicidad y potencia oncolítica. El VAO Ad-URR/E1AD24 mostró replicación y potente efecto citopático selectivo para líneas celulares PVH+ similares a las de los vectores más potentes, como el Ad-wt y el Ad-D24; en cuanto a selectividad, este vector es significativamente menos citotóxico para células PVH-. Se comprobó que la selectividad del vector se debe a un efecto sinérgico entre el promotor del PVH (URR) y la mutación en E1A. Finalmente, se confirmó su eficacia antitumoral en un modelo murino y se observó que este tratamiento puede tener un efecto sistémico en tumores distantes no inyectados |
| English abstract | Several human epithelial neoplasms are associated with high risk strains of human papillomavirus (HPV) such as cervical, anorectal, and other carcinomas. For some tumor types the current therapeutic tools are only palliative. Conditionally replicative adenoviruses (CRAds) are promising antineoplastic agents, which can also trigger confined antitumor effects. We constructed a series of CRAds driven by the upstream regulatory promoter region (URR) of an Asian-American variant of HPV-16, which contained different mutations at the E1A region (dl1015 and/or D24) and wild-type. All vectors were tested in vitro for viral replication and cytotoxicity. Viral DNA replication and E1A expression were also assessed by quantitative PCR. Finally, we confirmed the antitumoral efficacy of this vector in injected and noninjected xenotransplanted cervical tumors in a murine model for tumor regression and survival studies. A vector denominated Ad-URR/E1AD24 displayed a potent cytopathic effect associated with high selectivity for HPV+ cell lines. We found that the oncolytic effect of this CRAd was comparable to Ad-wt or Ad-D24, but this efficacy was significantly attenuated in HPV» cell lines, an effect that was contributed by the URR promoter. Ad-URR/ E1A-D24 was very effective to control tumor growth in both injected and non-injected tumors generated with two different HPV+ cell lines. CRAd Ad-URR/E1A-D24 is a highly selective vector for HPV+ cell lines and tumors that preserves the oncolytic efficacy of Ad-wt and Ad— D24. Our preclinical data suggest that this vector may be useful and safe for the treatment of tumors induced by HPV like cervical cancers |
| Disciplines: | Biología, Medicina |
| Keyword: | Virus, Oncología, Adenovirus, Neoplasias, Papilomavirus, Plásmidos, Citotoxicidad, Vectores biológicos |
| Keyword: | Biology, Medicine, Virus, Oncology, Adenovirus, Neoplasms, Papillomavirus, Cytotoxicity, Biological vectors, Plasmids |
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