Barrett's metaplasia

Jankowski, Janusz; Harrison, Rebecca; Perry, Ian; Balkwill, Frances R.; Tselepis, Chris

doi:10.1016/s0140-6736(00)03411-5

Cited by 305 publications

(237 citation statements)

References 55 publications

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“…Previous work in the normal squamous esophagus has suggested that stem cells reside in the basal layer and that their progeny become differentiated in the parabasal and superficial layers eventually to become effete [8][9][10] ( Figure 1A). Cycling cells are Ki-67+ve ( Figure 1B) and expression reflects cells in late G1, S, G2 and M phases: consequently a proportion of this population would have incorporated IdU at infusion.…”

Section: Idu Labelled Cells In the Normal Squamous Esophagusmentioning

confidence: 83%

“…[6][7][8][9][10] The area of stem cell biology is in major flux with competing and contradictory theories being reported monthly. In addition these workers use in vitro, animal and occasionally human model systems.…”

Section: Introductionmentioning

confidence: 99%

“…Despite these problems other techniques which trace lineage by genetic analyses strongly favour the likelihood of common stem cells between squamous and columnar esophageal mucosa [19][20][21][22][23][24] . The site of stem cells in BE has been more problematic [10][11][12][13][14][15] as well as the availability of true 'biomarkers' of stem cells [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

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Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

et al. 2013

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Background & Aims:The existence of slowly-cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients.Methods: Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg per m 2 body surface area, maximum dose of 400 mg) over a 30-min period; the IdU had a circulation t 1/2 of 8hs. Tissues were collected at 7, 11, 29 and 67 days following infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. Results:No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly, because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this timepoint. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine). Conclusions:LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia is required.4

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Section: Idu Labelled Cells In the Normal Squamous Esophagusmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

et al. 2013

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“…It must be emphasised, however, that this model does not apply to gastrooesophageal junction tumours. Gastro-oesophageal adenocarcinomas (Siewert Type I and II tumours) arise via a similar sequence of histopathological events, however, the initiating, promoting and molecular factors are different to gastric cancer carcinogenesis (Jankowski et al, 2000). Indeed, H. pylori appears to exert a protective role in these types of tumours (Chow et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor-1α expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas

et al. 2006

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Hypoxia-inducible factor-1 (HIF-1)a expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n ¼ 20), Helicobacter pylori associated gastritis (n ¼ 24), intestinal metaplasia (n ¼ 24), dysplasia (n ¼ 12) and intestinal (n ¼ 19) and diffuse (n ¼ 21) adenocarcinoma. The relationship between HIF-1a expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1a expression was not observed in normal gastric mucosa but increased in density (Po0.01) and intensity (Po0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P ¼ 0.034), advanced TNM stage (P ¼ 0.001) and was an adverse prognostic factor for cancer-specific survival (P ¼ 0.019). In univariate analysis and in comparison with tumours not expressing HIF-1a, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0À2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5À1.2). Hypoxia-inducible factor-1a lost prognostic significance in multivariate analysis. The results suggest HIF-1a is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.

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“…The majority of BM (Barrett's metaplasia) is acquired in adult life arising principally as a result of gastro-oesophageal reflux disease, although any insult that causes distal oesophageal irritation, such as chemical injury, is also permissive for metaplasia (Dixon et al, 2001;Goldblum et al, 1998). A common feature of acid and bile damage to the native oesophageal mucosa is a mixed inflammatory cell infiltrate especially around the stem cell rich areas of the basal mucosal compartment and papillae (Jankowski et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor-α in Barrett's oesophagus: a potential novel mechanism of action

et al. 2002

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Barrett's metaplasia (BM) is an early lesion in the progression from oesophageal inflammation through dysplasia to the development of Barrett's adenocarcinoma (BA). Previous work indicates that BM and BA are associated with reduced E-cadherin expression and increased cytoplasmic/nuclear pools of its associated protein b-catenin. b-catenin participates in Wnt signalling and activates oncogene transcription by complexing with T-cells factors (TCF). One such oncogene is c-myc. We have previously shown that TNF-a can downregulate E-cadherin expression. Here, we assess TNF-a expression in Barrett's metaplasia and examine if TNF-a can promote b-catenin mediated transcription of oncogenes in a gastrointestinal model system. Employing immunohistochemistry and Western blot analysis of oesophageal tissue, epithelial expression of TNF-a increases with progression along the metaplasia -dysplasia -carcinoma sequence (P50.001). b-catenin mediated transcription was then assessed in TNF-a stimulated cell lines using the TOPFLASH reporter system whilst cmyc expression was assessed by real time PCR. In a columnar intestinal cell model, TNF-a induces c-myc expression which is induced via b-catenin mediated transcription (P50.05). This b-catenin mediated transcription is independent of NF-kB activation. Thus, TNF-a is up-regulated in the progression of Barrett's oesophagus and b-catenin mediated transcription of cmyc is a novel pathway whereby elevated levels of TNF-a may lead to oncogene transcription and altered biology in gastrointestinal epithelia and metaplasia.

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Barrett's metaplasia

Cited by 305 publications

References 55 publications

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Hypoxia-inducible factor-1α expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas

Tumour necrosis factor-α in Barrett's oesophagus: a potential novel mechanism of action

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