RESUMEN
Expression levels of five miRNAs (miR-19b, miR-21, miR-126, miR-141, miR-205) were measured in the plasma of healthy donors and prostate cancer patients. It was shown that miR-141 expression level efficiently discriminates early stage prostate cancer patients and correlates with the Gleason score.
Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Próstata/genética , Biomarcadores de Tumor/sangre , Estudios de Cohortes , Diagnóstico Diferencial , Humanos , Modelos Logísticos , Masculino , MicroARNs/sangre , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Regulación hacia ArribaRESUMEN
Human Adenovirus type 6 (HAdV-C6) is a promising candidate for the development of oncolytic vectors as it has low seroprevalence and the intrinsic ability to evade tissue macrophages. However, its further development as a therapeutic agent is hampered by the lack of convenient cloning methods. We have developed a novel technology when a shuttle plasmid carrying the distal genome parts with modified E1A and E3 regions is recombined in vitro with the truncated HAdV-C6 genome. Using this approach, we have constructed a novel Ad6-hT-GM vector controlled by the hTERT promoter and expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) instead of 6.7K and gp19K E3 proteins. We have demonstrated that control by the hTERT promoter may result in delayed viral replication, which nevertheless does not significantly change the cytotoxic ability of recombinant viruses. The insertion of the transgene by displacing the E3-6.7K/gp19K region does not drastically change the expression patterns of E3 genes; however, mild changes in expression from major late promoter were observed. Finally, we have demonstrated that the treatment of human breast cancer xenografts in murine models with Ad6-hT-GM significantly decreased the tumor volume and improved survival time compared to mock-treated mice.
Asunto(s)
Adenovirus Humanos , Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Ratones , Animales , Adenovirus Humanos/genética , Estudios Seroepidemiológicos , Adenoviridae/genética , Adenoviridae/metabolismo , Transgenes , Regiones Promotoras Genéticas , Vectores Genéticos/genética , Viroterapia Oncolítica/métodos , Línea Celular Tumoral , Replicación Viral , Virus Oncolíticos/genética , Neoplasias/terapia , Neoplasias/genéticaRESUMEN
BACKGROUND/AIM: Oncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells. MATERIALS AND METHODS: Oncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively. RESULTS: Ad6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group. CONCLUSION: Ad6 was shown to be a promising agent for treating glioblastomas.