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1.
Asian Pac J Cancer Prev ; 17(8): 3711-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27644605

RESUMO

Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor- specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Inibidoras de Apoptose/genética , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Humanos , Neoplasias/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Interferência de RNA/efeitos dos fármacos
2.
Mol Biol Rep ; 43(9): 911-22, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27251218

RESUMO

As an ancient disease, tuberculosis (TB) is a major global health threat. Therefore, there is an urgent need for an effective and safe anti-TB vaccine. In the current study, a delivery system of Fc domain of mouse IgG2a and early secreted antigenic target protein 6 (ESAT-6) was evaluated for the selective uptake of antigens by antigen-presenting cells (APCs). Thus, it was based on the immunogenicity of a fusion protein. The study was initiated by the transfer of recombinant expression vectors of pPICZαA-ESAT-6:Fcγ2a and pPICZαA-ESAT-6: His into Pichia pastoris (P. pastoris). Recombinant proteins were assessed for immunogenicity following the immunoblotting analysis. High levels of IFN-γ and IL-12 were produced to induce Th1-type cellular responses through vaccination with both recombinant proteins [ESAT-6:Fcγ2a (EF) and ESAT-6:His (EH)]. The Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low increment in IL-4 compared to PBS, BCG, and EH groups. Although in all the immunized groups, the ratio of IFN-γ/IL-4 was in favor of Th1 responses, the highest Th1/Th2 balance was observed in EF immunized group. Fc fragment of mouse IgG2a may induce a selective uptake of APCs towards the cross-presentation and formation of Th1 responses in favor of an appropriate protective anti-tuberculosis reaction. Thus, further research on Fc-fusion proteins is required to develop Fc-based TB vaccines.


Assuntos
Fragmentos Fc das Imunoglobulinas/imunologia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/prevenção & controle , Vacinas de Subunidades Antigênicas/imunologia , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/imunologia , Feminino , Imunidade Celular , Interferon gama/sangue , Interleucina-12/sangue , Interleucina-4/sangue , Camundongos Endogâmicos C57BL , Pichia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/biossíntese , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Vacinação , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/biossíntese
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