Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro

Tselepis, Chris; Morris, Clive; Wakelin, Donald E.; Hardy, Richard J.; Perry, Ian; Luong, Quang T.; Harper, Elvin; Harrison, Rebecca; Attwood, S. E. A.; Jankowski, Janusz

doi:10.1136/gut.52.2.174

Cited by 130 publications

(118 citation statements)

References 26 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…Bile acids, particularly unconjugated bile acids such as DCA, are a component of gastro-duodenal reflux that have been strongly linked to BE development. [26][27][28] In previous studies, DCA showed the strongest effect on Cdx2 transcription of all bile acids. [29][30][31] In our earlier reports, we proposed that bile acids suppress the expression of Hes1 via Cdx2 activation in esophageal epithelial cells, with resulting activation of ATOH1 and MUC2.…”

Section: Discussionmentioning

confidence: 99%

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus

Tamagawa

Ishimura

Uno

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus

Tamagawa

Ishimura

Uno

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

“…In addition, myc overexpressing mice demonstrate increased incidence of tumours (Pelengaris et al, 1999). The expression of c-MYC in human oesophageal malignancy has previously been documented, demonstrating that c-MYC expression is elevated in Barrett's metaplasia and further overexpressed in oesophageal adenocarcinoma (Tselepis et al, 2003;Schmidt et al, 2007). The gene encoding c-MYC is located within chromosomal region 8q23 -24.2, a region frequently amplified in adenocarcinomas of the oesophagus and gastro-oesophageal junction and that has been detected in Barrett's metaplasia (Walch et al, 2000;Croft et al, 2002;Doak et al, 2003;van Dekken et al, 2006).…”

mentioning

confidence: 99%

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

et al. 2008

Self Cite

View full text Add to dashboard Cite

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT -PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT -PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/ MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model.

show abstract

“…Bile acids have been shown to be damaging to esophageal epithelial cells by affecting membrane permeability, cell proliferation and differentiation, increasing free radicals, inducing DNA damage and up-regulating oncogenes [11,[14][15][16][17][18][19][20]. More specifically, both gastric acid and bile acids have been shown to activate NF-kappa B, a major molecule that is up-regulated in and intrinsic to cancer development.…”

Section: Hpimentioning

confidence: 99%

A Favorable Response of Dysplastic Barrett’s Refractory to Ablation Therapy Only after Initiation of an Alginate Solution as Add-on Therapy

Brodie¹,

Elias²,

Khalaf³

et al. 2017

J Gastrointest Dig Syst

View full text Add to dashboard Cite

Alginates have been shown not only to be beneficial in their relief of symptomatic post-prandial gastroesophageal reflux, but there is also evidence that they may inhibit reflux, including bile acids and pepsin, and in turn attenuate and even prevent the activation and up-regulation of molecules associated with the development of metaplasia and cancer of the esophagus. Here we present the case of a patient with Barrett's esophagus with high-grade dysplasia (HGD) which was initially unresponsive to endoscopic radiofrequency ablation therapy and cryotherapy for highgrade dysplasia. Following initiation of therapy with an alginate solution in addition to twice daily proton pump inhibitor (PPI) therapy, the patient showed a favorable response and eventual complete eradication of his dysplastic Barrett's. The patient's course is suggestive that the alginate solution, through reflux inhibition, prevented persistent esophageal cell changes which occur secondary to gastric and bile acid exposure, thus allowing development of neosquamous epithelium. This case is intriguing with regard to the role of alginates in creating a favorable environment for esophageal healing when treating Barrett's esophagus with high-grade dysplasia. Keywords: Gastroesophageal reflux; Endoscopy; Proton pump inhibitor; Hernia Case Study HPIA.H. is a 46 year old male with history of hiatal hernia and gastroesophageal reflux disease (GERD) who presented to our tertiary referral center for management of long segment dysplastic Barrett's esophagus with high-grade dysplasia (HGD) which had been refractory to treatment with radiofrequency ablation (RFA). The patient had undergone five rounds of RFA at an outside medical center with less than 50% improvement of his dysplastic Barrett's at the time of the fifth endoscopy. His last endoscopy prior to transfer had revealed residual dysplastic Barrett's in the lower esophagus, and biopsies showed persistent HGD. On presentation to our center, the patient reported that his acid reflux was not well-controlled despite twice daily PPI. He complained of heartburn, night time regurgitation, and nonproductive cough. Review of systems was otherwise negative for chest pain, shortness of breath, dysphagia, odynophagia, weight loss, abdominal pain, nausea, vomiting, or other complaints. Treatment course: After a long discussion with the therapeutic endoscopy team, options other than RFA such as endoscopic mucosal resection and cryotherapy were discussed. Given the distribution, anatomy and flat nature of his Barrett's esophagus, cryotherapy was started and he began receiving treatments every two months starting in July 2014. After the first three treatments, there was minimal endoscopic evidence of improvement in the surface area of Barrett's epithelium with less than 50% improvement, so ablation exposure times were increased from 20 to 30 seconds.This still resulted in only mild improvement in appearance of his Barrett's after a total of six cryotherapy treatment sessions. Because of the lack of response, ma...

show abstract

Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro

Cited by 130 publications

References 26 publications

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus

Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett's esophagus

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

A Favorable Response of Dysplastic Barrett’s Refractory to Ablation Therapy Only after Initiation of an Alginate Solution as Add-on Therapy

Contact Info

Product

Resources

About