RESUMO
The use of conditionally replicative adenoviruses (CRAds) as a promising strategy for cancer gene therapy has been developed to overcome inefficient transduction of solid tumor masses by replication-deficient adenoviruses. Many modifications have been made to CRAds to enlarge tropism, increase selectivity and lytic ability, and improve safety. However, safety is still a concern in the context of future clinical application of CRAds. Particularly, after injection into the body, viral replication cannot be controlled externally. Therefore, we constructed a novel CRAd using a tetracycline-inducible promoter system to realize external pharmacological control of its replication. The effect of this CRAd in vitro was measured at the levels of viral DNA replication, cell death and progeny production. We showed that CRAd replication was tightly controlled by the presence or absence of doxycycline (Dox). Moreover, this system showed a significant gene expression in vivo, in which the viral replication was controlled by the oral administration of Dox. This strategy may help improve the safety of cancer gene therapy.
Assuntos
Adenoviridae/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Terapia Genética/métodos , Neoplasias/terapia , Regiões Promotoras Genéticas , Inibidores da Síntese de Proteínas/farmacologia , Replicação Viral/fisiologia , Adenoviridae/genética , Adenoviridae/crescimento & desenvolvimento , Adenoviridae/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Vetores Genéticos/genética , Células HeLa , Humanos , Tetraciclina/farmacologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/genéticaRESUMO
The effects of ultrasonic scaling in combination with povidone-iodine solution were examined clinically. The results obtained were as follows: 1. Three days after instrumentation, significant improvement was found in all experimental groups. Thereafter the improvement was at the same level and backing in each group. 2. Clinical findings, with exception of plaque index, showed improvement with ultrasonic scaling in combination with povidone-iodine solution in comparison with ultrasonic scaling alone and root planing.
