ABSTRACT
The most common inactivation mechanism of tumor suppressor genes, RASSF1A and p16INK4a, in lung cancer is hypermethylation. We detected the methylation status of RASSF1A and p16INK4a in serum of lung cancer patients using methylation-specific PCR and analyzed their clinicopathological significance. Each of RASSF1A and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in benign lung lesion patients. Hypermethylation was preferentially observed in small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a. In non-small cell lung cancer (NSCLC), RASSF1A and p16INK4a hypermethylation were found in 27% and 37.8% respectively. Hypermethylation of RASSF1A was not correlated with clinicopathological character. While, p16INK4a hypermethylation was associated with age >60 years, smoking and squamous cell carcinoma (SCC) (P = 0.033), but not with gender and pathological stages of NSCLC. Sensitivity and specificity of each gene were 31.1% and 100% respectively and the sensitivity improved with evaluation of a combination of the two genes (55.6%). These findings suggest that serum RASSF1A and p16INK4a hypermethylation are promising diagnostic method for detection of lung cancer. As regard the clinicopathological characteristics, p16INK4a hypermethylation may provide a more specific approach than RASSF1A hypermethylation.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , Lung Neoplasms/genetics , Promoter Regions, Genetic , Tumor Suppressor Proteins/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Cyclin-Dependent Kinase Inhibitor p16/metabolism , DNA , Humans , Lung Neoplasms/diagnosis , Tumor Suppressor Proteins/metabolismABSTRACT
The immunomodulatory effects of antibiotics could influence the degree of systemic and local responses to infection, so investigation of their intrinsic influence on the host's inflammatory response appears to be essential. Fluoroquinolones are known to exert modulatory activity on immune responses to microbial infection. However the mechanism of this immunmodulation has not been well elucidated. The aim of the work, is to assess the immunomodulatory effects of a levofloxacin, through examining its effect on the concentrations of tumor necrosis factor α (TNF-α) and Interleukin - 10 (IL-10) in serum of pneumonic patients. After following local research ethics committee approval and informed consent. This study included 40 patients with different types of pneumonia, admitted to department of Chest Diseases, Faculty of Medicine, Assiut University Hospitals, Egypt. Also, 10 healthy volunteers served as randomized controls. Both patients and controls received levofloxacin (750 mg once daily for 10 days). Serum levels of TNF-α and IL-10 were measured in patients and control before and after levofloxacin administration (750 mg once daily for 10 days) using human TNF-α and IL-10 ELISA kits respectively. Levofloxacin caused a statistically significant decrease in the mean level of TNF-α in both patients (20.82 ± 1.31 pg/ml) (P < 0.009) and control group (17.12 ± 0.84 pg/ml) (P < 0.004). In contrast, there was statistically significant increase (P < 0.000) in the mean level of IL-1 0 in patients (61.75 ± 2.85 pg/ml) while statistically significant decrease (P < 0.005) in control group (28.57 ± 1.37 pg/ml). In conclusion, our study demonstrates that treatment with levofloxacin affects production of TNF-α as a pro-inflammatory cytokine and IL-10 as an anti-inflammatory cytokines which may provide additional benefits in treatment of respiratory tract infections that are independent of its antibacterial properties.
