Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.
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PMID:Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation. 1258 Dec 49

Esophageal adenocarcinoma (EAC) is one of the most common malignancies in the world which is associated the increased prevalence of obesity. In the context of obesity, leptin can directly contribute to progression of EAC. Adiponectin inhibits leptin-induced oncogenic signaling in EAC cells. However, the exact molecular mechanisms linking obesity, adipokines, and EAC remain far from completely understood. In the present study, we tested the role of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) in adiponectin-induced protective effects against leptin-induced EAC cell proliferation. We found that globular adiponectin (gAD) significantly inhibited leptin-induced increase of cell proliferation and decrease of apoptosis in OE 19 cells. Moreover, leptin-induced increase of UHRF1 expression was suppressed by gAD. Compared with normal controls, UHRF1 expression was markedly increased in EAC tissues and cell lines. Silence of UHRF1 increased the expression of cleaved caspase 3 and 9 and Bax, reduced the expression of Bcl-2, promoted apoptosis, and inhibited cell proliferation in OE 19 cells. Overexpression of UHRF1 significantly blocked gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of adiponectin receptor 1/2 (AdipoR1/2) could inhibit gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of AdipoR2, but not AdipoR1, suppressed gAD-induced decrease of UHRF1 expression in leptin-treated cells. The results indicated that gAD inhibited the prooncogenic effects of leptin via AdipoR2-mediated suppression of UHRF1. Our study provides novel insights into the role of UHRF1 in the development of EAC and the mechanism of antitumor effect of gAD.
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PMID:Globular adiponectin inhibits leptin-stimulated esophageal adenocarcinoma cell proliferation via adiponectin receptor 2-mediated suppression of UHRF1. 2828 59