IntroductionInterleukin 1 beta (IL- 1β), a key proinflammatory cytokine encoded by the interleukin 1 beta gene, has been associated with chronic inflammation and plays an important role in lung inflammatory diseases including lung cancer. Elevated levels of Interleukin 1proteins, in particular interleukin 1 beta greatly enhance the intensity of the inflammatory response.AimTo study the role of interleukin 1 beta-31C > T and -511 T > C polymorphism in the pathogenesis of non small cell lung cancer (NSCLC).Materials and methodsOne hundred and ninety non small cell lung cancer patients and 200 healthy age, sex, smoking and dwelling matched controls were used for polymorphic analysis by polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. Normal tissues of 48 histopathologically confirmed non small cell lung cancer patients were taken for mRNA expression analysis. Quantitation of interleukin 1 beta was carried out by quantitative real time PCR.ResultThe T/T genotype of interleukin 1 beta-31 gene was significantly associated with increased risk of NSCLC [(P = 0.001, OR – 2.8 (95%CI 1.52–5.26)]. The interleukin 1 beta − 511 T > C does not show any difference between the NSCLC and control group (P = 0.3, OR – 0.72 (95%CI 0.41–1.28). Quantitative analysis of mRNA showed significant association with interleukin 1 beta T allele as compared to the interleukin 1 beta-31C allele (P = 0.006).ConclusionWe conclude that lung cancer risk genotype interleukin 1 beta-31TT results in increased expression of interleukin 1 beta mRNA in lung cancer patients. Our data suggest that this genotype (IL1β -31TT) in the interleukin 1 beta regulatory region provide a microenvironment with elevated inflammatory stimuli and thus increasing the risk for lung cancer.
O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.
This study describes the experiences of 10 young feminised men in Pakistan. They face high levels of stigma, violence and sexual abuse. The average age of first sex was 11 years old and all reported having been been raped during childhood and early adolescence, often several times. While some mothers and siblings were quietly supportive, young feminised men often end up running away from home, finding support as a member of a hijra dera, a 'pseudo-household' led by an older feminised man or guru, in which they find employment as dancers or sex workers. After their entry into sex work there is little or no opportunity to use condoms. The hijra dera offer an important entry point for improved social support and sexual health programmes, including efforts to ensure young feminised men postpone their sexual debut and/or improve their sexual health, retain access to education, explore alternative forms of employment and improve access to health care.
BackgroundSeveral studies suggest that Vitamin D (Vit-D3) supplementation reduces Chronic Urticaria (CU) symptoms.ObjectivesEvaluation of serum 25-hydroxyvitamin-D (25 (OH)2D) level and assessment of therapeutic effect of VitD3in CU patients.Methods192 subjects were stratified according to the baseline 25(OH)2D levels and subsequently randomized into three subgroups to receive Vit-D3 alone (VD) or antihistamine and systemic corticosteroid (H+S) or VitD3 with antihistamine and systemic corticosteroid (VD+H+S) for 6 weeks between July 2012 to Oct 2014. 130 healthy controls (HC) were followed without any intervention. The patients were evaluated for reduction in urticarial symptoms using visual analogue scale (VAS) and 5-D itch score.ResultsLow serum levels of 25 (OH)2D was observed in 91% of CU patients and 64% of the healthy controls (P < 0.0001). VAS and 5-D Score in subgroups VD, H + S and VD + H + S decreased significantly from 6 · 7 ± 0 · 043, 6 · 6 ± 0 · 42 and 6 · 68 ± 0 · 40 at baseline to 5 · 2 ± 0 · 70 (P = 0 · 0088), 3 · 3 ± 0 · 50 (P < 0 · 0001) and1 · 86 ± 0 · 39 (P < 0 · 0001) after treatment and from 14 · 5 ± 0 · 72, 13 · 9 ± 0 · 77 and 13 · 9 ± 0 · 221 to 12 · 06 ± 1 · 10 (P = 0 · 0072), 8 · 1 ± 1 · 13 (P < 0 · 0001) and 5 · 01 ± 0 · 94 (P < 0 · 0001) respectively.ConclusionsCU patients have low serum 25(OH)2D levels and Vit-D3 supplementation in combination with antihistamine and systemic corticosteroid show elevated response in resolving the symptoms of CU. This study also warrants that each subject with CU should be screened for serum 25 (OH)2D levels before starting a treatment.
Aim: The implications of molecular biomarkers IDH1/2 mutations and MGMT gene promoter methylation were evaluated for prognostic outcome of glioma patients. Materials & methods: Glioma cases were analyzed for IDH1/2 mutations and MGMT promoter methylation by DNA sequencing and methylation-specific PCR, respectively. Results: Mutations found in IDH1/2 genes totaled 63.4% (N = 40) wherein IDH1 mutations were significantly associated with oligidendrioglioma (p = 0.005) and astrocytoma (p = 0.0002). IDH1 mutants presented more, 60.5% in MGMT promoter-methylated cases (p = 0.03). IDH1 mutant cases had better survival for glioblastoma and oligodendrioglioma (log-rank p = 0.01). Multivariate analysis confirmed better survival in MGMT methylation carriers (hazard ratio [HR]: 0.59; p = 0.031). Combination of both biomarkers showed better prognosis on temozolomide (p < 0.05). Conclusion: IDH1/2 mutations proved independent prognostic factors in glioma and associated with MGMT methylation for better survival.
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