Wyniki wyszukiwania

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Barrett's esophagus associates with a variant of IL23R gene

100%

Gaj P., Mikula M., Wyrwicz L. S., Regula J., Ostrowski J.

Acta Biochimica Polonica

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2008

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tom 55

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nr 2

365-369

Gastroesophageal reflux disease is regarded as a spectrum of diseases: non-erosive reflux disease (NERD), erosive reflux disease (ERD), and the far end of the spectrum represented by patients with Barrett’s esophagus. Among predisposing factors, both risk and protective polymorphic variants of several genes may influence the clinical outcomes of reflux disease. Consequently, different molecular mechanisms are likely to underlie the development of clinical variants of reflux disease. Ninety six patients with reflux disease were screened for polymorphisms of CARD15, SLC22A4 (OCTN1), SLC22A5 (OCTN2), DLG5, ATG16L1 and IL23R genes which had previously been found to associate with immune-mediated chronic inflammatory disorders. While none of the polymorphisms were associated with NERD or ERD, the 1142G/A variant of the IL23R gene was found to be a risk variant in Barrett’s esophagus patients. The IL23/IL23R pathway may modulate STAT3 transcriptional activity which is an essential regulator not only of immune-mediated inflammation, but also of inflammatory-associated apoptosis resistance. Although the mechanisms of metaplastic transition of inflamed squamous epithelium are undetermined as yet, our findings suggest potential involvement of alternations in the IL23/IL23R pathway as a molecular background of Barrett’s esophagus development.

2

Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin

100%

Man Y.-M., Park J.-M., Kangwan N., Jeong M., Lee S., Cho J. Y., Ko W. J., Hahm K. B.

Journal of Physiology and Pharmacology

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2015

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tom 66

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nr 2

3

Adiponectin and leptin receptors expression in Barrett's esophagus and normal squamous epithelium in realtion to central obesity status

100%

Mokrowiecka A., Sokolowska M., Luczak E., Dudojc M., Wieczfinska J., Kacprzak D., Wierzchniewska-Lawska A., Pawliczak R., Malecka-Panas E.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 2

4

Cyclooxygenase-2 [COX-2] is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects

80%

Majka J., Rembiasz K., Migaczewski M., Budzynski A., Ptak-Belowska A., Pabianczyk R., Urbanczyk K., Zub-Pokrowiecka A., Matlok M., Brzozowski T.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 4

409-418

Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage and inflammation progressing chronic esophagitis and premalignant Barrett's esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects. We evaluated the expression of COX-2 in rat model of BE and examined the usefulness of COX-2 expression in determining the risk of malignant transformation in patients with BE treated with argon plasma coagulation (APC) that allows for effective ablation of metaplastic mucosa (group A) without or with proton pump inhibitors (PPI). In addition, the group B of patients was subjected to laparoscopic Nissen's fundoplication and group K that served as control, received PPI treatment only. Expression of COX-2 was evaluated in fresh-frozen biopsy specimens obtained from the distal esophagus in all 60 patients before and 12 months after treatment. In experimental studies, eighty rats were surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was evaluated by macroscopic and histological index score, the plasma IL-1ß and TNF- levels was determined by ELISA and the mucosal expression of COX-2 mRNA and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic esophagitis was developed in all EGDA animals followed by the rise in the plasma TNF- and IL-1ß levels. Histology revealed extensive esophageal ulcerations with development of columnar epithelium, formation of mucus glands in squamous epithelium, intestinal metaplasia distant to anastomosis consisting of goblet cells, infiltration of inflammatory cells including plasma cells and lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control animals but strongly upregulated in metaplastic Barrett's epithelium. In BE patients, the overexpression of COX-2 was documented in patients with dysplasia. After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2 mRNA was markedly reduced and these effects were positively correlated with histopathological findings. Controls failed to show significant alterations in COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of the chronic esophagitis by the gastrointestinal refluxate resembling many features of those observed in human Barrett's esophagus, as confirmed by severe morphology changes, excessive release of proinflammatory cytokines TNF- and IL-1ß and overexpression of COX-2, and 2) the significant correlation of the degree of COX-2 overexpression with histopathological findings indicates the usefulness of this inducible biomarker as a valuable indicator of the risk of malignant transformation in patients with BE.

Ograniczanie wyników

Barrett's esophagus associates with a variant of IL23R gene

Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin

Adiponectin and leptin receptors expression in Barrett's esophagus and normal squamous epithelium in realtion to central obesity status

Cyclooxygenase-2 [COX-2] is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects