Correlation between promoter methylation of p14ARF, TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma

<p>Abstract</p> <p>Background</p> <p>To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma.</p> <p>Patients and Methods</p> <p>Out of 36 cases cholangiocarcinoma patients from April 2000 to May 2005 were collected.Promoter hypermethylation of <it>DAPK</it>, <it>p14^ARF</it>, and <it>ASC </it>were detected by methylation-specific PCR on cholangiocarcinoma and normal adjacent tissues samples. Mutation of the p53 gene was examined by automated sequencing. Correlation between methylation of these genes and/or <it>p53 </it>mutation status with clinical characteristics of patients was investigated by statistical analysis.</p> <p>Results</p> <p>We found 66.7% of 36 cholangiocarcinoma patients had methylation of at least one of the tumor suppressor genes analyzed. <it>p53 </it>gene mutation was found in 22 of 36 patients (61.1%). Combined <it>p53 </it>mutation and <it>DAPK, p14^ARF, and/or ASC </it>methylation was detected in 14 cases (38.9%). There were statistically significant differences in the extent of pathologic biology, differentiation, and invasion between patients with combined <it>p53 </it>mutation and <it>DAPK, p14^ARF, and/or ASC </it>methylation compared to those without (P < 0.05). The survival rate of patients with combined <it>DAPK, p14^ARF, and ASC </it>methylation and <it>p53 </it>mutation was poorer than other patients (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Our study indicates that methylation of <it>DAPK, p14^ARF, and ASC </it>in cholangiocarcinoma is a common event. Furthermore, <it>p53 </it>mutation combined with <it>DAPK, p14^ARF, and/or ASC </it>methylation correlates with malignancy and poor prognosis.</p

TETANUS IMMUNIZATION AMONG PREGNANT WOMEN: COVERAGE RATE AND RATE OF PROTECTION AT TIME OF DELIVERY

Objective: Even though attempts have been effectively applied to eradicate the neonatal tetanus through widespread childhood vaccination and improved conditions at delivery, it remains major cause of infant mortality and continues a problem of public health in developing countries including Yemen.&nbsp; The aims of this study were to determine the tetanus immunization status, the association between the risk factors and failure of protection in pregnant women at time of delivery. Methods: This cross-sectional study included 476 women seeking care for delivery at Al Thawra Modern General Hospital and Al Sabain Hospital, women age ranged from 16-49 years old. Immunization information and factors affecting it were obtained through a standard questionnaire. Serum samples were collected and level of IgG antibody against Clostridium tetani was measured by ELISA technique. Protected women were defined as those with serum antibody levels &gt;or=0.6 IU/ml. Results: The total vaccine covering rate of tetanus was 87%, and maternal vaccine rate was 33.6%, the protective rate at time of delivery was 68.5%. There were significant association between unvaccinated (OR=18.6), older ages (OR=1.7), rural residency (OR=34) and malaria infection during pregnancy (OR=2.9); with protection failure in pregnant women at time of delivery. Conclusion: It can be concluded that the total vaccine coverage rate and antenatal tetanus vaccine rate were insufficient. In addition, the protective rate at time of delivery was low and large numbers of neonate are susceptible to neonatal tetanus and death. Vaccinating every pregnant woman with at least one dose of TT would be an affordable and effective way to protect against neonatal tetanus, and would be a step toward eliminating the deaths that continue to occur due to this preventable disease in Yemen. &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; Peer Review History: Received 2 February 2018; &nbsp;&nbsp;Revised 21 February; Accepted 1 March, Available online 15 March 2019 Academic Editor: Dr. Marwa A. A. Fayed,&nbsp;University of Sadat City, Egypt,&nbsp;[email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:&nbsp; &nbsp; &nbsp; &nbsp; Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.5/10 Reviewer(s) detail: Dr. Ahmad Abdelsattar El-Ebiary, Tanta University Hospitals, Tanta, Egypt, [email protected] Dr. George Zhu,&nbsp;Tehran University of Medical Sciences, Tehran, Iran, [email protected] Comments of reviewer(s): &nbsp;Similar Articles: THE PREVALENCE OF VULVOVAGINAL CANDIDIASIS IN PREGNANT WOMEN ATTENDING SEVERAL HOSPITALS IN SANA’A, YEMEN PREVALENCE OF CYTOMEGALOVIRUS IGG ANTIBODIES, POTENTIAL RISK FACTORS AND AWARENESS OF CONGENITAL CYTOMEGALOVIRUS AMONG FEMALE DOCTOR

Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case–control analysis

PURPOSES: We conducted a case–control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). METHODS: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant’Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class. RESULTS: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73–13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83–5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures. CONCLUSIONS: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years

The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

<p>Abstract</p> <p>Background</p> <p>Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.</p> <p>Methods</p> <p>Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.</p> <p>Results</p> <p>The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).</p> <p>Conclusion</p> <p>The homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.</p

Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma

Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered as potential therapeutic targets in cholangiocarcinoma, but no studies have yet clarified the clinicopathological or prognostic significance of these molecules. Immunohistochemical expression of these molecules was assessed retrospectively in 236 cases of cholangiocarcinoma, as well as associations between the expression of these molecules and clinicopathological factors or clinical outcome. The proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4, 53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and 8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively. Clinicopathologically, EGFR overexpression was associated with macroscopic type (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate analysis showed that EGFR expression was a significant prognostic factor (hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.52–4.69; P=0.0006) and also a risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05–3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma

Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma

Bile duct cells and hepatocytes differentiate from the same hepatic progenitor cells. To investigate the possible association of viral hepatitis B and C with intrahepatic cholangiocarcinoma (ICC), we conducted a retrospective case–control study using univariate and multivariate logistic analyses to identify risk factors for ICC. Besides hepatic lithiasis (25.6%; P<0.001), seropositivity for hepatitis B surface antigen (37.5% of all ICC patients; odds ratio (OR) =4.985, P<0.001) and seropositivity for hepatitis C antibodies (13.1%; OR=2.709; P=0.021) are the primary independent risk factors for ICC. Cirrhosis exerted synergic effects on the development of ICC. We compared the age distributions of viral-hepatitis associated ICC to that of viral hepatitis-associated hepatocellular carcinoma (HCC). The mean age of ICC patients with viral hepatitis B (56.4±11.1 years) were 9 years younger than that of ICC patients with viral hepatitis C (65.6±9.17 years), similar to that observed in HCC. The incidence ratio of HCC : ICC : CHC (combined hepatocellular cholangiocarcinoma) in our population was 233 : 17 : 1 consistent with the theoretic ratio of hepatocyte number to cholangiocyte number in the liver. Our findings indicated that both viral hepatitis-associated ICC and HCC shared common disease process for carcinogenesis and, possibly, both arose from the hepatic progenitor cells