RESUMO
OBJECTIVE: The role of the cytokine, macrophage migration inhibition factor (MIF) was assessed in tuberculosis. This case-control study investigated whether commonly occurring functional MIF polymorphisms are associated with active tuberculosis as well as with serum levels of MIF, IFN-γ and TNF-α. METHODS: Two MIF promoter polymorphisms, a functional -794 CATT5-8 microsatellite repeat (rs5844572) and a -173G/C single-nucleotide polymorphism (rs755622), were analysed by PCR and PCR-RFLP, respectively, in 47 patients and 50 healthy subjects. The mRNA level of MIF was performed by real-time PCR (RT-PCR), and MIF, IFN-γ and TNF-α serum levels were determined by ELISA. RESULTS: A significant increase of MIF mRNA expression and MIF protein level were found in patients compared to healthy controls. Meanwhile, the increase of IFN-γ and TNF-α serum levels were confirmed. According to the profile of genetic model, a significant association was found of genotypes carrying the -794 CATT 7 or 8 and -173 C risk alleles with susceptibility to active tuberculosis and with a significant increase of MIF, IFN-γ and TNF-α. CONCLUSIONS: These data suggested a distinct genetic and immunopathogenic basis for tuberculosis at the MIF locus. Serum MIF, IFN-γ and TNF-α profiles distinguish tuberculosis from the more inflammatory phenotype and may play a role in pathogenesis and as biomarkers of active tuberculosis.
Assuntos
Interferon gama/sangue , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Tuberculose Pulmonar/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Tuberculose Pulmonar/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To construct chimerical DNA vaccine plasmid of human papillomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. METHODS: Molecular cloning techniques were used to construct recombinant plasmid pcDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection.IL-2 and gamma-INF secreted by immunized spleens lymphocyte and HPV 11 L1 or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. RESULTS: The chimerical DNA plasmid of pcDNA3 L1-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and gamma-INF were detected in vaccinated mice. CONCLUSION: Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.
Assuntos
Engenharia Genética , Papillomavirus Humano 11/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/genética , Vacinas contra Papillomavirus/imunologia , Vacinas de DNA/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Sequência de Bases , Feminino , Papillomavirus Humano 11/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Distribuição Aleatória , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genéticaRESUMO
AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P<0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P<0.05). CONCLUSION: ERCC1 codon 118 polymorphism has no significant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.