RESUMO
OBJECTIVE: To investigate the therapeutic effect of herpes simplex virus thymidine kinase (HSV-TK) gene mediated by synthetic radiation-inducible promoters in the treatment of oral squamous cell carcinoma (OSCC) in vitro and in vivo. METHODS: The plasmids pcDNA3.1(+)E6-HSV-TK were constructed, in which the HSV-TK genes were mediated by synthetic radiation-inducible promoters. The recombined plasmids were transfected into the Tca8113 cells and golden hamster buccal carcinoma, respectively. Low-dose radiotherapy was used to upregulate the HSV-TK genes expression. HSV-TK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical method. RESULTS: Compared with control group, the comparative survival rate of Tca8113 cells in HSV-TK/GCV/IR group was markedly decreased and the golden hamster buccal carcinoma in HSV-TK/GCV/IR group was obviously suppressed. Up-regulation of HSV-TK gene expression was found in the Tca8113 cells and in the golden hamster buccal carcinoma resulting from exposure to low-dose irradiation. The apoptosis indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly lower than those without irradiation. CONCLUSION: The results indicate that the synthetic radiation-inducible promoters can serve as a molecular switch to adjust the expression of HSV-TK gene in the treatment of OSCC, and low-dose induction radiation can significantly improve therapeutic efficiency.
Assuntos
Carcinoma de Células Escamosas/terapia , Terapia Genética , Neoplasias Bucais/terapia , Simplexvirus/enzimologia , Timidina Quinase/uso terapêutico , Animais , Apoptose/fisiologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/fisiologia , Cricetinae , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica/genética , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Vetores Genéticos/genética , Humanos , Neoplasias Bucais/patologia , Plasmídeos/genética , Antígeno Nuclear de Célula em Proliferação/análise , Regiões Promotoras Genéticas/genética , Regiões Promotoras Genéticas/efeitos da radiação , Doses de Radiação , Simplexvirus/genética , Timidina Quinase/genética , Transfecção/métodos , Regulação para Cima/efeitos da radiaçãoRESUMO
We present Experiment 864's measurement of invariant antideuteron yields in 11.5A GeV/c Au+Pt collisions. The analysis includes 250x10(6) triggers representing 14x10(9) 10% central interactions sampled for events with high mass candidates. We find (1/2pip(t))d(2)N/dydp(t) = 3.5+/-1.5(stat)+0.9-0.5(syst)x10(-8) GeV-2 c(2) for 1.8