Development of the therapy for oral cancer by transduction of iNOS gene in combination with radiotherapy

点击翻译按钮获取中文摘要

1. Transfection of human oral squamous cell carcinoma cells (B88) with the gene encoding inducible nitric oxide synthase (INOS) resulted in the suppression of cell growth and NO production in vitro or in nude mice. The effect of overexpression of iNOS gene on B88 cells was augmented by irradiation, while down-regulation of iNOS gene in B88 cells caused significantly the enhancement of cell growth.2. In transfection of iNOS gene to B88 cells, bystander effect on the tumor cells without expression of iNOS gene was detected.3. We have already reported the high effectiveness of the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy. When we examined immunohistochemically the expression of iNOS in the biopsy materials taken at the first visit to our clinic, group with complete remission showed the strong expression of iNOS in the inflammatory cells infiltrating into the subepithellal region.4. We found that a lipoteichoic acid-related molecule (OK-PSA) prepared from streptococcal agent, OK-432 is a potent inducer of Th1-type cytokines.5. When human salivary cancer (HSG) ?bearing nude mice were administered OK-PSA peritumorally, production of Th1 type cytokines such as IFN-γ, , TNF-α, IL-2, IL-12 or IL-18 as well as of nitrite/nitrate was detected in the blood, in which radiotherapy augmented production of the cytokines and NO.6. Treatment with OK-PSA of human peripheral blood mononuclear cells, U937 cells, human gingival fibroblasts or human oral squamous carcinoma cells (BHY) resulted in production of N0_2^-.7. Cultivation of B88 cells under the presence of NO donor (NOC18 ; 0.01-1mg/ml) caused potent induction of apoptosis.