ABSTRACT
BACKGROUND: Cervical cancer is highly associated with human papillomavirus (HPV) E6 and E7 gene expression. We have previously reported two antisense oligodeoxynucleotides (AS-ODNs) directed against adjacent targets within the HPV-16 E6/E7 mRNA (419 and 434), each able to downregulate HPV-16 E6/E7 mRNA in vitro and in vivo and to specifically inhibit tumor cell growth in culture and animal models. METHODS: Towards potential clinical application and improved in vivo performance, we analyzed the effect of the combined treatment of 419-434 AS-ODNs on the anchorage independent growth (AIG) of HPV-16-positive cervical carcinoma cell lines. RESULTS: We found similar responses between combined 419-434 and individual AS-ODNs treatments in RNaseH assays, cell uptake, and in vivo degradation of HPV-16 E6/E7 transcripts. Moreover, the combined use of 419-434 AS-ODNs resulted in additive AIG inhibition of CaSki and SiHa cells, similar to that obtained with equivalent doses of the individual AS-ODNs. CONCLUSIONS: By using a combined treatment, it may be possible to overcome the potential mutations frequently reported within HPV-16 genome, thus improving the potential application of 419 and 434 AS-ODNs as a therapeutic alternative for cervical cancer.
Subject(s)
Carcinoma/therapy , Carcinoma/virology , Genetic Therapy/methods , Human papillomavirus 16/growth & development , Human papillomavirus 16/genetics , Oligodeoxyribonucleotides, Antisense/pharmacology , Oligodeoxyribonucleotides, Antisense/therapeutic use , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/virology , Cell Line, Tumor , Down-Regulation , Drug Therapy, Combination , Female , Gene Expression Regulation, Viral/drug effects , Humans , RNA, Messenger , RNA, ViralABSTRACT
Introducción. La hipoplasia dérmica focal o síndrome de Goltz es una displasia que afecta tejidos de origen ectodérmico y mesodérmico; muestra herencia dominante ligada al cromosoma X con latelidad in utero para los varones y en las mujeres presenta expresividad variable. Los varones afectados han correspondido a los primeros casos en la familia, por lo que se ha postulado una mutación de media cromátide en estadios tempranos de la embriogénesis con el fin de explicar el mosaico somático y germinal presente en los pacientes. Caso clínico. Se describe el caso de un varón afectado con una genodermatosis caracterizada por hipoplasia de dermis que sigue las líneas de blaschko, talla baja, microcefalia, asimetría facial, microftalmía derecha, persistencia de membrana pupilar, camptodactilia, sindactilia cutánea, hipotricosis, displasia ungueal e hipoplasia de esmalte. Se discuten los mecanismos hereditarios implicados con fines de asesoramiento genético en varones afectados. Conclusión para fines de asesoramiento genético, los riesgos para hipoplasia dérmica focal, sobre todo en casos esporádicos, deben establecerse en base a herencia dominante ligada al cromosoma X, a menos que el árbol genealógico sugiera otro patrón de transmisión hereditaria
