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| 1 | MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma显示文摘Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer. | Cameron M Smith David I Watson Michael Z Michael Damian J Hussey | 2010 | World Journal of Gastroenterology2010，16，5： | 23 |
| 2 | miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus显示文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium. | Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven Damian J Hussey | 2011 | World Journal of Gastroenterology2011，17，8： | 13 |
| 3 | MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines显示文摘AIM:To investigate expression of microRNA(miRNA)and potential targets in chemotherapy resistant esoph-ageal cancer cell lines.METHODS:An in-vitro model of acquired chemotherapy resistance in esophageal adeno-(EAC)and squamous cell carcinoma(ESCC)cells was used,and microRNA expression profiles for cisplatin or 5-fluorouracil(5-FU)resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction(PCR).The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated.RESULTS:Chemotherapy resistant sublines were found to have specific miRNA signatures,and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line,and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent.Amongst others,miR-27b-3p,miR-193b-3p,miR-192-5p,miR-378 a-3p,miR-125a-5p and miR-18a-3p were dysregulated,consistent with negative posttranscriptional control of KRAS,TYMS,ABCC3,CBL-B and ERBB2 expression via these miRNAs.CONCLUSION:The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer. | Richard Hummel Corina Sie David I Watson Tingting Wang Alfiya Ansar Michael Z Michael Mark Van der Hoek Joerg Haier Damian J Hussey | 2014 | World Journal of Gastroenterology2014，20，40： | 8 |
| 4 | Estrogen,male dominance and esophageal adenocarcinoma:Is there a link?显示文摘Esophageal adenocarcinoma is a cancer with poor prognosis,and its incidence has risen sharply over recent decades.Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors.It is possible that a difference in the expression of estrogen,or its signaling axes,may contribute to this gender bias.We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression,and the possible sex-specific links with esophageal adenocarcinoma development.Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression,and the effect of crosstalk between estrogen and leptin signaling were identified.We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development.The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma,but further studies are required. | Huiqi Yang Olga A Sukocheva Damian J Hussey David I Watson | 2012 | World Journal of Gastroenterology2012，18，5： | 7 |
| 5 | Lymph node metastases of adenocarcinoma of the esophagus and esophagogastric junction显示文摘背景食道的腺癌正在成为日益重要的 problem.It 大多数很快在最后十年在西方的国家一直在增加恶意,并且它的预后是这研究的 poor.The 目的是为食管和 esophagogastric 连接的腺癌评估在肿瘤侵略深度和淋巴节点转移之间的关系,并且学习组与 aden 包括了 121 个病人在 patients.Methods | ZHANG Xun David I Watson Glyn G Jamieson | 2007 | Chinese Medical Journal2007，，24： | 7 |
| 6 | From blood to breath: New horizons for esophageal cancer biomarkers显示文摘Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma subtypes. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers. | Roger Yazbeck Simone E Jaenisch David I Watson | 2016 | World Journal of Gastroenterology2016，22，46： | 6 |
| 7 | MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett's esophagus显示文摘AIM To investigate the micro RNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett's esophagus.METHODS High throughput screening using Taq Man~ Array Human Micro RNA quantitative PCR was used to determine expression levels of 754 micro RNAs in distal esophageal mucosa(1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett's esophagus using argon plasma coagulation vs pretreatment mucosa, posttreatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett's esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted m RNA target pathway analysis was used to investigate the functional involvement of differentially expressed micro RNAs.RESULTS Forty-four micro RNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen micro RNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine micro RNAs(mi R-424-5p, mi R-127-3p, mi R-98-5p, mi R-187-3p, mi R-495-3p, mi R-34c-5p, mi R-223-5p, mi R-539-5p, mi R-376a-3p, mi R-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These micro RNAs were also more highly expressed in Barrett's esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these micro RNAs may be involved in the regulation of cell survival signalling pathways. Three micro RNAs(mi R-187-3p, mi R-135b-5p and mi R-31-5p) were expressed at higher levels in postablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These mi RNAs were expressed at similar levels in preablation Barrett's esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these micro RNAs may be involved in regulating the expression of proteins that contribute to barrier function.CONCLUSION Neosquamous mucosa arising after ablation of Barrett's esophagus expresses micro RNAs that may contribute to decreased barrier function and micro RNAs that may be involved in the regulation of survival signaling pathways. | Loveena Sreedharan George C Mayne David I Watson Timothy Bright Reginald V Lord Alfiya Ansar Tingting Wang Jakob Kist David StJ Astill Damian J Hussey | 2017 | World Journal of Gastroenterology2017，23，30： | 3 |
| 8 | Androgens and esophageal cancer: What do we know?显示文摘Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer. | Olga A Sukocheva Bin Li Steven L Due Damian J Hussey David I Watson | 2015 | World Journal of Gastroenterology2015，21，20： | 2 |
| 9 | Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus显示文摘BACKGROUND Circulating microRNAs(miRNAs)are potential biomarkers for many diseases.However,they can originate from non-disease specific sources,such as blood cells,and compromise the investigations for miRNA biomarkers.While small extracellular vesicles(sEVs)have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery,the most suitable blood sample for sEV miRNA biomarker studies has not been defined.AIM To compare the mi RNA profiles between matched serum and plasma s EV preparations to determine their suitability for biomarker studies.METHODS Matched serum and plasma samples were obtained from 10 healthy controls and10 patients with esophageal adenocarcinoma.s EV isolates were prepared from serum and plasma using Exo Quick TM and quantified using Nano Sight.RNA was extracted from s EV preparations with the mi RNeasy Serum/Plasma kit and profiled using the Taqman Openarray q PCR.The overall mi RNA content and theexpression of specific mi RNAs of reported vesicular and non-vesicular origins were compared between serum and plasma s EV preparations.The diagnostic performance of a previously identified multi-mi RNA biomarker panel for esophageal adenocarcinoma was also compared.RESULTS The overall mi RNA content was higher in plasma s EV preparations(480 mi RNAs)and contained 97.5%of the mi RNAs found in the serum s EV preparations(412 mi RNAs).The expression of commonly expressed mi RNAs was highly correlated(Spearman’s R=0.87,P<0.0001)between the plasma and serum s EV preparations,but was consistently higher in the plasma s EV preparations.Specific blood-cell mi RNAs(hsa-mi R-223-3 p,hsa-mi R-451 a,mi R-19 b-3 p,hsa-mi R-17-5 p,hsa-mi R-30 b-5 p,hsa-mi R-106 a-5 p,hsa-mi R-150-5 p and hsa-mi R-92 a-3 p)were expressed at 2.7 to 9.6 fold higher levels in the plasma s EV preparations compared to serum s EV preparations(P<0.05).In plasma s EV preparations,the percentage of protein-associated mi RNAs expressed at relatively higher levels(Ct 20-25)was greater than serum s EV preparations(50%vs 31%).While the percentage of vesicle-associated mi RNAs expressed at relatively higher levels was greater in the serum s EV preparations than plasma s EV preparations(70%vs 44%).A 5-mi RNA biomarker panel produced a higher cross validated accuracy for discriminating patients with esophageal adenocarcinoma from healthy controls using serum s EV preparations compared with plasma s EV preparations(AUROC 0.80 vs 0.54,P<0.05).CONCLUSION Although plasma s EV preparations contained more mi RNAs than serum s EV preparations,they also contained more mi RNAs from non-vesicle origins.Serum appears to be more suitable than plasma for s EV mi RNAs biomarkers studies. | Karen Chiam George C Mayne Tingting Wang David I Watson Tanya S Irvine Tim Bright Lorelle T Smith Imogen A Ball Joanne M Bowen Dorothy M Keefe Sarah K Thompson Damian J Hussey | 2020 | World Journal of Gastroenterology2020，26，20： | 1 |
| 10 | 澳大利亚微创胆道外科(英文)显示文摘目的从20世纪末期以来,澳大利亚腹腔镜手术已经快速发展进步并且逐渐扩展到各个外科手术领域。一些外科医生也完成并发表了关于腹腔镜胆总管探查技术的报道。在本文中,作者介绍了目前澳大利亚的微创外科手术治疗胆管疾病的现状,包括:常规或选择性胆管造影;胰腺胆道疾病中ERCP的作用;腹腔镜胆总管探查术的手术技巧以及胆源性胰腺炎的治疗。作者还介绍了澳大利亚目前胆总管探查的现状,并且提到他们倾向于每例腹腔镜胆囊切除术都进行术中胆道造影。如果胆总管内发现小结石而且胆囊管足够粗,则进行经胆囊管的胆总管探查术。然而,如果狭窄的胆总管内有较大的结石,则进行术后ERCP治疗。作者还进一步介绍了胆道疾病相关的其他的微创治疗手术方法。总的来说,腹腔镜手术进行胆总管取石是可行和安全的。在有足够经验的医疗中心,这种手术方法可以常规使用。同时,成功进行腹腔镜胆总管探查术也需要多种方法综合进行。ERCP也没有被腹腔镜胆总管探查术所取代,而且成为一种重要的补充性的胆总管结石治疗方法。 | David I Watson John W Chen | 2007 | 中国微创外科杂志2007，7，8： | 0 |
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