PurposeThe promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology.MethodsThe promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR® green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed.ResultsSignificant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Δmeth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%).ConclusionMethylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer.

Hepatitis C Virus is a causative agents of liver cirrhosis, having highly diversified genome. Genotype study has important role in clinical setup and prognosis of hepatitis C virus infection. The aim of this was to investigate the prevalence and risk factors associated with hepatitis C virus genotypes in district Kohat, Khyber Pakhtunkhwa, Pakistan. Hepatitis C virus pre-infected patients (n = 600) were analyzed to assess circulating HCV genotypes, using reverse transcriptase approach. Moreover serum ALT levels were determined followed by correlation with genotypes. In current study cohort, majority of patients (62%) were, having elevated ALT (> 50 U/L). similarly patients with mixed HCV genotypes, 3a/3b have relatively higher ALT levels (~62) compared to 2a/3a (~43) and others. We found significant correlation (p = 0.002) of genotype 2a in connection with ALT (49.48) level. Similarly 3a, 3b, mixed as well as untypeable genotypes correlations were also found highly significant (p <0.001) with their mean ALT levels (47.14, 31.58, 46.69 and 43.68) respectively. In our studied population, most prevalent genotypes were 3a (25%) followed by 3b (20%) and 2a (15%). Fifteen percent of patient's infections were untypeable while in 10% patients mixed genotype were observed. Among total 30 (5%) were blood transfusion cases, 90(15%) surgical, 540 (90%) dentistry, 360 (60%) Barber, 492 (82%) Pricks, whereas 180 (30%) cases were those having early type of HCV/HBV infection in their family. In current study, genotypes 3a and 3b were more prevalent, with two potential risk factors; dentistry and barbers. Moreover, genotypes and ALT investigations were found to be more fruitful in prognosis as well as management of HCV infection.

Introduction: Laparoscopic cholecystectomy is the treatment of choice forsymptomatic cholelithiasis. Intraperitoneal instillation of bupivacaine is one of the methods usedto improve pain relief after laparoscopic cholecystectomy. Objective: To compare the mean painscore after intraperitoneal instillation of bupivacaine with placebo during laparoscopiccholecystectomy. Study Design: Randomized Control trial. Setting: This study was carried out asurgical unit PGMI Lady Reading Hospital and Hayatabad Medical Complex, Peshawar.Duration: The duration of study was 6 months from 15th May to 15th December, 2013. Subjectsand Methods: 92 patients in each group were included in study to compare the mean pain scoreof intraperitoneal instillation of bupivacaine (Group A; study group) with 0.9% normal salinesolution (Group B; placebo group) using visual analogue scale after laparoscopiccholecystectomy at 12th hour after surgery. Data was entered in software SPSS version 16.0. Ttest was used to compare the mean pain scores. Results: The mean age of patients in Group Aand B was 41.82 ± 7.34 and 40.95 ± 9.24 respectively (p=0.483). Group A has low mean painscore (3.619 ± 0.676) according to Visual Analogue Scale then Group B (3.837 ± 0.667) with astatistically significant p value (p=0.036). A t test failed to reveal a statistically reliable differencebetween gender (p=0.513) and age (p=0.767) wise distribution of mean pain between group Aand B. Conclusions: Mean pain score of intraperitoneal instillation of bupivacaine is significantlyless than 0.9% normal saline solution at 12th hour after laparoscopic cholecystectomy.

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