Decreased expression of 17β-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon

<p>Abstract</p> <p>Background</p> <p>The importance of 17β-estradiol (E2) in the prevention of large bowel tumorigenesis has been shown in many epidemiological studies. Extragonadal E2 may form by the aromatase pathway from androstenedione or the sulfatase pathway from estrone (E1) sulfate followed by E1 reduction to E2 by 17-β-hydroxysteroid dehydrogenase (HSD17B1), so <it>HSD17B1 </it>gene expression may play an important role in the production of E2 in peripheral tissue, including the colon.</p> <p>Methods</p> <p><it>HSD17B1 </it>expression was analyzed in colorectal cancer cell lines (HT29, SW707) and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of <it>HSD17B1 </it>using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of <it>HSD17B1 </it>CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1) in to E2 was determined by electrochemiluminescence method.</p> <p>Results</p> <p>We found a significant decrease in HSD17B1 transcript (<it>p </it>= 0.0016) and protein (<it>p </it>= 0.0028) levels in colorectal cancer (CRC) from the proximal but not distal colon and rectum. This reduced <it>HSD17B1 </it>expression was associated with significantly increased DNA methylation (<it>p </it>= 0.003) in the CpG rich region located in the 5' flanking sequence of the <it>HSD17B1 </it>gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of <it>HSD17B1</it>, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation.</p> <p>Conclusions</p> <p>Our results showed that reduced <it>HSD17B1 </it>expression can be associated with DNA methylation in the 5' flanking region of <it>HSD17B1 </it>in CRC from the proximal colon.</p

Estrogen-dependent regulation of sodium/hydrogen exchanger-3 (NHE3) expression via estrogen receptor β in proximal colon of pregnant mice

Although constipation is very common during pregnancy, the exact mechanism is unknown. We hypothesized that the involvement of estrogen receptor (ER) in the regulation of electrolyte transporter in the colon leads to constipation. In this study, the intestines of normal female ICR mouse and pregnant mice were examined for the expression of ERβ and ERβ by immunohistochemistry and in situ hybridization. ERα, but not ERα, was expressed in surface epithelial cells of the proximal, but not distal, colon on pregnancy days 10, 15, and 18, but not day 5, and the number of ERα-positive cells increased signiWcantly during pregnancy. Expression of NHE3, the gene that harbors estrogen response element, examined by immunohistochemistry and western blotting, was localized in the surface epithelial cells of the proximal colon and increased in parallel with ERβ expression. In ovariectomized mice, NHE3 expression was only marginal and was up-regulated after treatment with 17- estradiol (E2), but not E 2 + ICI 182,780 (estrogen receptor antagonist). Moreover, knock-down of ERβ expression by electroporetically transfected siRNA resulted in a signiWcant reduction of NHE3 expression. These results indicate that ERβ regulates the expression of NHE3 in the proximal colon of pregnant mice through estrogen action, suggesting the involvement of increased sodium absorption by up-regulated NHE3 in constipation during pregnancy

Two cameras detect more lesions in the small-bowel than one

AIM: To explore the feasibility of dual camera capsule (DCC) small-bowel (SB) imaging and to examine if two cameras complement each other to detect more SB lesions. METHODS: Forty-one eligible, consecutive patients underwent DCC SB imaging. Two experienced investigators examined the videos and compared the total number of detected lesions to the number of lesions detected by each camera separately. Examination tolerability was assessed using a questionnaire. RESULTS: One patient was excluded. DCC cameras detected 68 positive findings (POS) in 20 (50%) cases. Fifty of them were detected by the &quot;yellow&quot; camera, 48 by the &quot;green&quot; and 28 by both cameras; 44% (n = 22) of the &quot;yellow&quot; camera&apos;s POS were not detected by the &quot;green&quot; camera and 42% (n = 20) of the &quot;green&quot; camera&apos;s POS were not detected by the &quot;yellow&quot; camera. In two cases, only one camera detected significant findings. All participants had 216 findings of unknown significance (FUS). The &quot;yellow&quot;, &quot;green&quot; and both cameras detected 171, 161, and 116 FUS, respectively; 32% (n = 55) of the &quot;yellow&quot; camera&apos;s FUS were not detected by the &quot;green&quot; camera and 28% (n = 45) of the &quot;green&quot; camera&apos;s FUS were not detected by the &quot;yellow&quot; camera. There were no complications related to the examination, and 97.6% of the patients would repeat the examination, if necessary. CONCLUSION: DCC SB examination is feasible and well tolerated. The two cameras complement each other to detect more SB lesions. © 2011 Baishideng. All rights reserved

A meta-analysis evaluating the accuracy of colon capsule endoscopy in detecting colon polyps

Background: Colon capsule endoscopy (CCE) is a new, noninvasive method for examining the entire colon. The reported yield of CCE in detecting colorectal polyps has shown variable results. Objective: To assess the accuracy of CCE by pooling data of existing trials. Design: Meta-analysis. The fixed-effects or random-effects model was used as appropriate, based on whether homogeneity or heterogeneity, respectively, was indicated by the Cochran Q test. Setting: Studies that estimated the accuracy of CCE were identified. Two investigators independently conducted the search and data extraction. Patients: A total of 626 individuals were included in this meta-analysis. Intervention: Each patient underwent CCE and conventional colonoscopy. Main Outcome Measurements: Per-patient sensitivity and specificity, with 95% confidence intervals (CI). Results: Findings were categorized as &quot;significant polyps,&quot; that is, a report of a polyp &gt;6 mm in size or 3 or more polyps of any size, or &quot;any polyp,&quot; that is, a report of any polyp found, independent of size. Pooled data on sensitivity and specificity with a 95% CI were estimated. For any polyp found, the pooled data showed per-patient CCE sensitivity of 73% (95% CI, 68%-77%) and specificity of 89% (95% CI, 81%-94%). For significant polyps, the respective values were 69% (95% CI, 62%-75%) and 86% (95% CI, 82%-90%). Limitations: A small number of studies met inclusion criteria. Conclusion: CCE is a reasonable method for screening asymptomatic individuals for colorectal polyps. It may be particularly useful for patients with &quot;incomplete&quot; colonoscopy, those with contraindications for conventional colonoscopy, and those unwilling to undergo colonoscopy because of its perceived inconvenience and discomfort. © 2010

Chemotherapy for recurrent cervical cancer

Purpose: Cervical cancer is the second most common cancer of women worldwide and one of the leading cause of death in relative young women. This review gives an outline of chemotherapy of advanced, persistent or recurrent cervical cancer. Methods: We performed a literature search in the PubMed of almost all relevant articles concerning chemotherapy of advanced, persistent or recurrent cervical cancer. Results: The available data from the literature is mainly composed of most recent reviews, phase II and randomized phase III clinical trials. Conclusion: Single-agent cisplatin remains the current standard therapy for advanced, persistent or recurrent cervical cancer. Several single-agents have been tested, but none has been found to be superior compared to cisplatin. Both topotecan and paclitaxel in combination with cisplatin, have yielded superior response rates and progression-free survival without diminishing patient quality of life. However, only the combination of cisplatin and topotecan has improved overall survival. It is important to identify clinical and tumor-related factors predictive of response to cisplatin-based chemotherapy. Future trials are necessary, not only to compare combinations of existing agents, but to incorporate biological agents (monoclonal antibodies or small molecules) to chemotherapy in order to improve the treatment results of advanced, persistent or recurrent cervix cancer. © 2008 Elsevier Ltd. All rights reserved

Does purgative preparation influence the diagnostic yield of small bowel video capsule endoscopy?: A meta-analysis

OBJECTIVES: Video capsule endoscopy (VCE) is a useful tool in investigating small bowel pathology. However, the role of bowel preparation is controversial. Therefore, the aim of this study was to explore the role of bowel preparation and in particular its consequences on diagnostic yield in a meta-analysis of all relevant studies. METHODS: Extensive English-language medical literature searches were performed up to February 2008, using suitable keywords, looking for human studies that compared different modes of small bowel preparation (purgative vs. clear liquids diet). We examined the effects of this preparation on the following three primary end points, diagnostic yield (DY), small bowel visualization quality (SBVQ), and VCE completion rate (CR) by meta-analysis of relevant studies. RESULTS: A total of 12 eligible studies (6 prospective, 6 retrospective) were identified, including 16 sets of data relevant to our primary end points. There were significant differences between patients prepared with purgative vs. those prepared with clear liquids diet in DY (263 vs. 213 patients, respectively; OR (95 CI)1.813 (1.251-2.628), P0.002) and SBVQ (404 vs. 249 patients, respectively; OR (95 CI)2.113 (1.252-3.566), P0.005). There was no statistically significant difference regarding CR rate. Purgatives did not affect VCE gastric transit time (GTT) or VCE small bowel transit time (SBTT). CONCLUSIONS: Pooled data showed that in comparison to clear liquids diet, purgative bowel cleansing, before VCE, improves the SBVQ and increases the DY of the examination, but does not affect the VCE completion rate. © 2009 by the American College of Gastroenterology

Contribution of nuclear morphometry by confocal laser scanning microscopy to the diagnosis of malignant bile duct strictures

Objective To determine the clinical utility of nuclear morphometry by confocal laser scanmnig microscopy for the diagnosis of malignant biliary strictures. Study Design The study included 51 patients with bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP). Based on the initial workup, 6 patients were diagnosed with benign strictures, and 12 patients had malignant strictures, while in the remaining 33 cases the diagnoses were inconsistent, due mainly to inadequate samples. Smears from ERCP brushings were stained for DNA with propidium iodide. Nuclear morphometry was assessed on images acquired by a confocal laser scanning microscope. Three parameters-nuclear volume, nuclear shape and nuclear staining intensity-were calculated. Based on these features, a distinctive nuclear morphometric pattern was attributed to the malignant nuclei, and its predictive value was assessed prospectively in the 33 undiagnosed cases. Results After an overall median follow-up period of 8 months, 19 patients were diagnosed with malignant strictures, and 14 patients were considered to have benign strictures. With respect to the prediction of malignancy, the sensitivity of the described method was 78%, the specificity was 63%, the positive predictive value was 64%, and the negative predictive value was 80%. Conclusion Nuclear morphometry may provide significant information for the diagnosis of malignant bile duct strictures when conventional cytology fails to. © The International Academy of Cytology