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MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

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World journal of Gastroenterology 2010年第5期16卷 531-537页

作者： Cameron M Smith David I Watson Michael Z Michael damian j hussey Department of Surgery Flinders University Room 3D211 Flinders Medical Centre Bedford Park South Australia 5042 Australia Department of Gastroenterology & Hepatology Flinders University Bedford Park South Australia 5042 Australia

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.

关键词： Barrett’s esophagus MicroRNA Esophageal adenocarcinoma Transdifferentiation Tumour suppressor

Androgens and esophageal cancer: What do we know?

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World journal of Gastroenterology 2015年第20期21卷 6146-6156页

作者： Olga A Sukocheva Bin Li Steven L Due damian j hussey David I Watson Flinders University Department of Surgery Flinders Medical Centre

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.

关键词： Esophageal cancer Androgens Androgenreceptor

miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus

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World journal of Gastroenterology 2011年第8期17卷 1036-1044页

作者： Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven damian j hussey Department of Surgery Flinders University Bedford Park Department of Gastroenterology and Hepatology Flinders University Bedford Park Department of Surgery Erasmus Medical Centre

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 jacent 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.

关键词： miRNA Barrett’s esophagus Esophageal adenocarcinoma miR-200 Epithelial to mesenchymal transition Apoptosis Proliferation Epithelium

MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

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World journal of Gastroenterology 2014年第40期20卷 14904-14912页

作者： Richard Hummel Corina Sie David I Watson Tingting Wang Alfiya Ansar Michael Z Michael Mark Van der Hoek joerg Haier damian j hussey Department of Surgery Flinders University Bedford Park South Australia 5042 Australia Department of General and Visceral Surgery University of Muenster 48149 Muenster Germany Department of Gastroenterology and Hepatology Flinders University 5042 Bedford Park South Australia Australia Adelaide Microarray Centre SA Pathology 5000 Adelaide South Australia Australia Comprehensive Cancer Centre University of Muenster 48149 Muenster Germany

AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines.

关键词： Esophageal cancer MicroRNA Chemotherapy Resistance Target

MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett's esophagus

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World journal of Gastroenterology 2017年第30期23卷 5508-5518页

作者： 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 Department of Surgery Flinders Medical Centre Flinders University St Vincent’s Centre for Applied Medical Research Department of Anatomical Pathology Flinders Medical Centre

To investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett’s esophagus. METHODSHigh throughput screening using TaqMan® Array Human MicroRNA quantitative PCR was used to determine expression levels of 754 microRNAs 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, post-treatment 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 mRNA target pathway analysis was used to investigate the functional involvement of differentially expressed microRNAs. RESULTSForty-four microRNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen microRNAs 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 microRNAs (miR-424-5p, miR-127-3p, miR-98-5p, miR-187-3p, miR-495-3p, miR-34c-5p, miR-223-5p, miR-539-5p, miR-376a-3p, miR-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These microRNAs 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 microRNAs may be involved in the regulation of cell survival signalling pathways. Three microRNAs (miR-187-3p, miR-135b-5p and miR-31-5p) were expressed at higher levels in post-

关键词： Neosquamous Barrett’s esophagus Ablation

Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus

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World journal of Gastroenterology 2020年第20期26卷 2570-2583页

作者： 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 Discipline of Surgery College of Medicine and Public HealthFlinders University of South AustraliaAdelaideSA 5042Australia Flinders Health and Medical Research Institute Cancer Program College of Medicine and Public HealthFlinders UniversityAdelaideSA 5042Australia Discipline of Surgery The University of AdelaideAdelaideSA 5005Australia Adelaide Medical School The University of AdelaideAdelaideSA 5005Australia Faculty of Health Sciences The University of AdelaideAdelaideSA 5005Australia

BACKGROUND Circulating microRNAs(miRNAs)are potential biomarkers for many ***,they can originate from non-disease specific sources,such as blood cells,and compromise the investigations for miRNA *** 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 *** To compare the mi RNA profiles between matched serum and plasma s EV preparations to determine their suitability for biomarker *** 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 *** was extracted from s EV preparations with the mi RNeasy Serum/Plasma kit and profiled using the Taqman Openarray q *** 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 *** diagnostic performance of a previously identified multi-mi RNA biomarker panel for esophageal adenocarcinoma was also *** 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 *** 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

关键词： Biomarkers Exosomes Extracellular vesicles Circulating microRNA MicroRNAs Plasma Serum Blood cells Real-time polymerase chain reaction Adenocarcinoma of esophagus

Speculations on the mechanisms for the formation and breakup of supercontinents

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Geoscience Frontiers 2013年第2期4卷 185-194页

作者： j.Brendan Murphy R.damian Nance Department of Earth Sciences.St.Francis Xavier University Antigonish.Nova Scotia B2G 2W5Canada Department of Geological Sciences Ohio UniversityAthensOH 45701USA

The supercontinent cycle has had a profound effect on the Earth＇s evolution since the Late Archean but our understanding of the forces responsible for its operation remains *** appear to form by two end-member processes：extroversion,in which the oceanic lithosphere surrounding the supercontinent（exterior ocean） is preferentially subducted（***）,and introversion in which the oceanic lithosphere formed between dispersing fragments of the previous supercontinent（interior ocean） is preferentially subducted（***）.Extroversion can be explained by ＂top-down＂ geodynamics, in which a supercontinent breaks up over a geoid high and amalgamates above a geoid low. Introversion,on the other hand,requires that the combined forces of slab-pull and ridge push（which operate in concert after supercontinent break-up） must be overcome in order to enable the previously dispersing continents to turn *** may begin when subduction zones are initiated along boundaries between the interior and exterior oceans and become trapped within the interior *** speculate that the reversal in continental motion required for introversion may be induced by slab avalanche events that trigger the rise of superplumes from the core-mantle boundary.

关键词： Supercontinent cycle Introversion Extroversion Pangea Rodinia Pannotia

Origins of the supercontinent cycle

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Geoscience Frontiers 2013年第4期4卷 439-448页

作者： R.damian Nance j.Brendan Murphy Department of Geological Sciences.316 Clippinger Laboratories.Ohio University.Athens.OH 45701.USA Department of Earth Sciences st.Francis Xavier UniversityAntigonishNova Scotia B2G 2W5.Canada

The supercontinent cycle, by which Earth history is seen as having been punctuated by the episodic assembly and breakup of supercontinents, has influenced the rock record more than any other geologic phenomena, and its recognition is arguably the most important advance in Earth Science since plate tectonics. It documents fundamental aspects of the planet＇s interior dynamics and has charted the course of Earth＇s tectonic, climatic and biogeochemical evolution for billions of years. But while the widespread realization of the importance of supercontinents in Earth history is a relatively recent development, the supercontinent cycle was first proposed thirty years ago and episodicity in tectonic processes was recognized long before plate tectonics provided a potential explanation for its occurrence. With interest in the supercontinent cycle gaining momentum and the literature expanding rapidly, it is instructive to recall the historical context from which the concept developed. Here we examine the supercontinent cycle from this perspective by tracing its development from the early recognition of long-term epi- sodicity in tectonic processes, through the identification of tectonic cycles following the advent of plate tectonics, to the first realization that these phenomena were the manifestation of episodic superconti- nent assembly and breakup.

关键词： Supercontinent cyclePlate tectonicsTectonic episodicitySecular trends

Surgical resection of rectal adenoma:A rapid review

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World journal of Gastroenterology 2009年第31期15卷 3851-3854页

作者： damian Casadesus Calixto Garcia Hospital J and University

Transanal excision （TE）, endoscopic transanal resection （ETAR） and transanal endoscopic microsurgery （TEN） can be used to remove adenomatous polyps. However, their use is limited by the size or location of the tumor. TE is limited to the lower rectum, TEN offers better access to lesions in the middle and upper rectum, and ETAR is used less frequently than it deserves for resection of rectal lesions.

关键词： Adenoma Colorectal surgery Endoscopy Gastrointestinal Microsurgery Rectal neoplasms