RESUMO
Survival after pancreatic cancer remains poor despite incremental advances in surgical and adjuvant therapy, and new strategies for treatment are needed. Oncolytic virotherapy is an attractive approach for cancer treatment. In this study, we have evaluated the effectiveness of the Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of vaccinia virus was effective against all human pancreatic carcinoma cells tested in vitro, especially those insensitive to oncolytic adenovirus. The virus displayed inherently high selectivity for cancer cells, sparing normal cells both in vitro and in vivo, with effective infection of tumors after both intravenous (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin-angiostatin fusion protein was confirmed in a pancreatic cancer model both in vitro and in vivo, with evidence of inhibition of angiogenesis. This novel vaccinia virus showed significant antitumor potency in vivo against the Suit-2 model by i.t. administration. This study suggests that the novel Lister strain of vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential therapeutic agent for pancreatic cancer.
Assuntos
Terapia Genética/métodos , Terapia Viral Oncolítica/métodos , Neoplasias Pancreáticas/terapia , Vaccinia virus/genética , Angiostatinas/genética , Animais , Fusão Gênica Artificial , Terapia Combinada , Endostatinas/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/patologia , Proteínas Recombinantes de Fusão , Células Tumorais Cultivadas , Vaccinia virus/fisiologia , Replicação Viral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Attention to viral infection of the male genital tract has been renewed over the last 15 years as a result of the prolific ongoing research on AIDS. Epidemiological studies of the virus in sperm and male genital tract contributes to the understanding of STD physiopathology and helps assessing their impact on male fertility. Recent advances in this field have allowed to offer Assisted reproductive techniques to couples with chronic viral infection, under strict and specific protocols. This paper presents an overview of these recent developments.