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1.
EXCLI J ; 19: 750-761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636728

RESUMO

Gastric cancer is the first cause of cancer-related death in males and the second in female patients in Iran. Advanced cancer is usually associated with distant metastasis, which is uncontrollable. This study was conducted to compare the expression of Scinderin and Gelsolin genes between gastric cancer and adjacent normal tissue samples in Iranian patients in order to better understand the role of these genes in this disease and to assess them as potential gastric cancer diagnostic or prognostic biomarkers. This case-control study was conducted in 41 Iranian patients suffering from stage I to IV of Gastric Cancer diagnosed by pathologic and endoscopic tests. In this study, significant down-regulation of Gelsolin (p=0.001) and over-expression of Scinderin (p=0.001) were observed in tumor tissues compared to the adjacent normal tissues. The results of the present study showed decreased Gelsolin expression in patients above 40 years, while the relationship between Gelsolin expression and age was not significant; also, a significant increase was observed in Scinderin expression in patients above 40 years. Furthermore, Lymph node metastasis was observed in 59.52 % of the cases. The results showed that reduced Gelsolin and increased Scinderin expression were related to lymph node metastasis. Based on results, a significant association was observed between tumor size and Scinderin expression level. Furthermore, Gelsolin and Scinderin expressions were assessed in different grades and stages to determine the association of this gene with cancer progression. The result indicates significant alteration in Scinderin expression level of I and IV, II and IV, and III and IV stages. Although no significant association was observed between Scinderin expression level and GC grade, the mean Gelsolin expression showed a significant difference between grade II and III as well as grade I and IV. Based on our results, these genes would be potential biomarkers.

2.
J Clin Immunol ; 30(1): 132-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19898928

RESUMO

INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease. MATERIALS AND METHODS: Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2-6), NBK/BIK gene (exons 2-5), and BAX gene (exons 1-7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer's instructions (Applied Biosystems). RESULTS: Eight of fifty Iranian AT patients (16%) exhibited a C > T transition in exon 2 (c342C > T) of the BAK gene, while none of the healthy controls had such alteration (P = 0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G > A) was also identified in 68% of the patient group versus 24% in the controls (P < 0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P = 0.0023). Another variant IVS1146C > T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P < 0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3 + 14A > G) was also significantly higher in the AT patients (P < 0.0001). DISCUSSION: Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/imunologia , Proteínas de Membrana/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética , Adolescente , Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Ataxia Telangiectasia/fisiopatologia , Criança , Análise Mutacional de DNA , Progressão da Doença , Éxons/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Inteínas/genética , Irã (Geográfico) , Masculino , Proteínas de Membrana/imunologia , Proteínas Mitocondriais , Mutação/genética , Polimorfismo Genético , Proteína Killer-Antagonista Homóloga a bcl-2/imunologia , Proteína X Associada a bcl-2/imunologia
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