No abstract

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.

Hypertension is the most important public health problem in developing countries and one of the major risk factors for cardiovascular diseases, and it has been reported that hypertension is in part an inflammatory disorder and several workers have reported elevated levels of CRP in hypertensive individuals. The main aim of the present study was to evaluate the association between blood pressure and serum CRP levels across the range of blood pressure categories including prehypertension. A total of 104 patients and 63 control subjects were included in the present study. The level of CRP in the serum samples was estimated by a high sensitivity immunoturbidometric assay. Standard unpaired student's 't' test was used for comparison of hs-CRP levels between hypertensive patients and normotensive control subjects and between patient groups with different grades of hypertension and different durations of hypertensive histories. The mean serum hs-CRP level in hypertensive patients was 3.26 mg/L compared with 1.36 mg/L among normotensive control subjects (P<0.001). On comparison with normotensive control subjects, the hs-CRP levels vary significantly both with grades and duration of hypertension, with most significant difference found in patients with prehypertension (P<0.001), followed by Stage-I (P=0.01) and Stage-II(P=0.02) hypertensives. Significant difference in hs-CRP levels was also found in patients with shorter duration of hypertensive history (≤ 1year) when compared with those with ≥5 years of hypertensive history (P<0.01). Our study reveals a graded association between blood pressure and CRP elevation in people with hypertension. Individuals with prehypertension or with shorter duration of hypertension (≤1 Year) had significantly a greater likelihood of CRP elevation in comparison to chronic stage-I or stage-II hypertensives.

Cancer is a major burden worldwide but there are marked geographical variations in frequency and incidence overall. The aim of this study was to find the frequency and distribution of commonly occurring cancers in Kashmir, with particular emphasis on urinary bladder cancer. A total of 4,407 cases of histologically confirmed new cancer cases were registered at the Medical Records Department (MRD) of SKIMS from a period between January, 2005 and April 2010. Among 4407 cancers, 2,457 (55.7 %) were men and 1,950 (44.3 %) were women. Stomach cancer is the leading one with an average frequency of 19.2 % followed by esophagus and lung as 16.5 % and 14.6 %, respectively. Stomach (23 %) and lung (21 %) are the leading cancers in men while as esophageal cancer tops (18.3 %) in women followed by breast cancer (16.6 %). This distribution of cancer types is strikingly different from that in the rest of India where oropharyngeal cancer is most common form. Among urinogenital cancers, bladder cancer was observed to primarily affect Kashmiri population (5.9 %) followed by prostate cancer (2.1 %) and renal carcinoma (1.1 %). We conclude that Kashmir is a very high risk area of most commonly occurring cancers particularly cancers of gastrointestinal tract which comprise more than half the frequency of all the cancers.

Our results indicate that MGMT promoter hypermethylation and concomitant loss of MGMT protein expression may play an important role in the development of gastric cancer in the Kashmiri population. High salt tea consumption may be a risk factor.