Detection of methylation of the RAR-ß gene in patients with non-small cell lung cancer.

The aim of this study was to detect methylation of the RAR-ß gene in tissues from non-small cell lung cancer (NSCLC) patients. The methylation of the RAR-ß gene in DNA from 80 cases with NSCLC and corresponding non-malignant tissues was tested using methylation-specific polymerase chain reaction (PCR; MSP). The results showed that the total frequency of RAR-ß methylation was significantly higher in lung cancer tissues compared to the corresponding non-malignant tissues (57.5 vs. 17.5%) (P<0.01). However, no significant difference was found in various clinical stages and types of lung cancer (P>0.05). A significant difference was observed in the various pathological types (P<0.05). RAR-ß gene methylation is closely correlated with the development process of NSCLC, particularly squamous cell carcinoma.

Combined effects of serum trace metals and polymorphisms of CYP1A1 or GSTM1 on non-small cell lung cancer: a hospital based case-control study in China.

INTRODUCTION: The limited information for effects of serum trace elements and genetic polymorphisms on lung cancer is available. Based on a hospital based case-control study, the epidemiological questionnaires were completed by face to face interview, and the gene polymorphisms were tested by RFLP-PCR, and serum trace metals were measured by atomic absorption spectrophotometer, and the data was analyzed by the logistic regressive models. RESULTS: The high serum copper level (>1500 ng/ml) or serum copper/zinc ratio (>1) was the risk factors of NSCLC (OR=3.10, 11.03, respectively), but the ORs of the higher serum Zn (>1200 ng/ml), Se (>50 ng/ml) or Cr(3+) (>600 ng/ml) for NSCLC were all significantly less than 0.20 (all p<0.01) indicating strong protection against NSCLC. While the OR of CYP 1A1 variants carriers with a higher serum Cu or Cu/Zn ratio level was around 3.38 and 12.59, respectively, the risk of CYP1A1 variants carriers with a higher serum Zn is 0.18, Se 0.04 or Cr(3+) 0.28. Similarly, compared with the carriers of GSTM1 power with a lower serum Zn, Se or Cr(3+), the OR of the carriers of GSTM1 null with a higher serum Zn, Se and Cr(3+) was separately 0.16, 0.07 and 0.26, highlighting the protection against NSCLC. CONCLUSIONS: Our findings suggested that CYP1A1 or GSTM1 variants may significantly modify the associations between level of serum trace metals (Cu, Zn, Se or Cr) and NSCLC, indicating the intriguing pathogenesis of lung cancer.

Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China.

BACKGROUND: Cigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are also considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear. METHODS: We collected the data of 150 cases and 150 age-matched and sex-matched controls on a Hospital-Based Case-Control Study in China. Face to face interviews were conducted using a standardized questionnaire. Gene polymorphism and methylation status were measured by RFLP-PCR and MSP, respectively. Logistic regressive model was used to estimate the odds ratios (OR) for different levels of exposure. RESULTS: After adjusted age and other potential confounding factors, smoking was still main risk factor and significantly increased 3.70-fold greater risk of NSCLC as compared with nonsmokers, and the ORs across increasing levels of pack years were 1, 3.54, 3.65 and 7.76, which the general dose-response trend was confirmed. Our striking findings were that the risk increased 5.16, 8.28 and 4.10-fold, respectively, for NSCLC with promoter hypermethylation of the p16, DAPK or RAR beta gene in smokers with CYP1A1 variants, and the higher risk significantly increased in smokers with null GSTM1 and the OR was 17.84 for NSCLC with p16 promoter hypermethylation, 17.41 for DAPK, and 8.18 for RAR beta in smokers with null GSTM1 compared with controls (all p < 0.01). CONCLUSION: Our study suggests the strong combined effects of cigarette smoke, CYP1A1 and GSTM1 Polymorphisms, hypermethylations of p16, DAPK and RAR beta promoters in NSCLC, implying complex pathogenesis of NSCLC should be given top priority in future research.

Oral respiratory syncytial virus (RSV) DNA vaccine expressing RSV F protein delivered by attenuated Salmonella typhimurium.

Human respiratory syncytial virus (RSV) is a major viral pathogen of the lower respiratory tract of infants and young children worldwide. No effective prevention measure is available. Attenuated Salmonella strains expressing heterologous antigens can be delivered by the oral route, triggering efficient antigen-specific humoral, cellular, and mucosal immunity. In this study, we orally administered attenuated Salmonella strain SL7207, carrying the plasmid pcDNA3.1/F expressing the RSV F gene, to BALB/c mice and showed significant elevations of serum anti-RSV IgG and bronchoalveolar lavage secretory IgA as compared with the control group carrying empty plasmid (p<0.001). The ratio of IgG1 and IgG2a was 0.96. The experimental group also showed a stronger cytotoxic T cell response (p<0.01 at effector:target ratios of 100:1 and 50:1) and a higher stimulation index value of T cell proliferation (p<0.05) than the respective control group. RSV titers in the lung homogenates of the experimental group on day 3 and day 5 postchallenge were lower than in the control group (p<0.05). Histopathological analysis showed obvious differences in infiltration of inflammatory cells and pulmonary alveolar wall thickness (p<0.01) between the two groups. In summary, our results demonstrate the potential of orally administered SL7207-based DNA vaccines against RSV infection.