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1.
Tissue Antigens ; 67(5): 368-76, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16671943

RESUMO

Immunogenicity of tumor cells is generally weak. Therefore, dendritic cells (DCs) have been used to boost anti-tumor responses of DC-based vaccines. DC function is highly dependent on its subsets and the level of its maturation. Nowadays, DC/tumor cell fusion vaccines are already used in clinical trials, and there are numerous studies discussing the effects of cytidine-phosphate-guanosine-containing oligonucleotides (CpG-ODN) on various cell types including DC. CpG-ODN a powerful immuno-stimulant can drive DCs fully mature, thus improve the efficacy of vaccine therapy. There are two simple ways to help load tumor antigens onto DCs by direct contact with cells themselves: fusion or co-culture of DCs with whole tumor cells. In this study, we combined these two approaches to improve the efficacy of DC/tumor cell-based vaccine. Mature DCs are adept at presenting processed Ag to T cells with loss of its capacity to capture Ag, while immature DCs are on the contrary. Our results emphasize the necessity of considering the stage of DC maturation and corresponding choice of tumor antigen delivery when designing approaches for prophylaxis or therapy of tumors using DC-based immunization protocols. We used CpG-ODN-1826-stimulated mature DCs and non-CpG-ODN-stimulating DCs as sources of tumor antigen carriers to investigate the appropriate Ag-loading ways between fusion and co-culture. Our results displayed that DC/tumor vaccine using CpG-ODN-stimulating mature DCs fused, not co-cultured, with tumor cells can generate a consistent and highly effective anti-tumor immune responses in vivo.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacinas Anticâncer/imunologia , Carcinoma Pulmonar de Lewis/imunologia , DNA/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Animais , Vacinas Anticâncer/uso terapêutico , Fusão Celular , Linhagem Celular Tumoral , Feminino , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Oligodesoxirribonucleotídeos , Ratos , Linfócitos T/imunologia
2.
Hua Xi Yi Ke Da Xue Xue Bao ; 20(4): 347-51, 1989 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-2698368

RESUMO

Oncogene of nasopharyngeal carcinoma (NPC) by means of external origin DNA transfection experiment and its gene products by immunohistochemical method have been studied. These DNAs were isolated from human primary poorly differentiated NPC tissues and were transfected into NIH/3T3 mouse fibroblasts to induce the foci of the morphologically transformed cells in the culture, while DNAs of normal placenta tissues failed to do so. The DNAs were extracted from the primary and secondary transformed cells to analyse human sequence with human Alu sequence probe. The human sequence has been detected in the DNAs of the primary and secondary transformed foci cells, while none of the human sequence was detected in the DNAs of the control. The results indicated that human transforming sequences had been integrated into transformed cells. The malignant properties of the transformed foci cells were evidenced by tumorigenic experiment of nude mice. The transformed foci cells were inoculated subcutaneously in the nude mice and induced fibrosarcoma in vivo. The tumorigenic rate was 87.5%. It was further demonstrated that DNAs from human NPC possessed carcinogenicity and induced malignant transformation. The primary result revealed that the transforming gene of NPC may be homologue to Ha-ras oncogene. The expression of Ha-ras gene products-p21 has been studied in human NPC tissues. The primary results showed a positive expression of p21 in human NPC tissues by immunohistochemical method. The positive rate was 90.4%.


Assuntos
Genes ras , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas/análise , Animais , DNA de Neoplasias/genética , Fibroblastos/citologia , Fibrossarcoma/etiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas p21(ras) , Transfecção
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