Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity and gastro-oesophageal reflux are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and ERK phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and ERK inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis.
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PMID:Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. 1761 45

Microvascular damage is one of the primary pathologic components of systemic sclerosis (SSc). Serological abnormalities of angiogenic and angiostatic factors in SSc have previously been described. Like these factors, the plasma levels of leptin were significantly elevated in patients with SSc in comparison to normal controls. However, leptin receptor has not been examined in patients with SSc. The current study used sandwich ELISA to evaluate the serum levels of leptin receptor in patients with SSc. Serum samples were obtained from 36 patients with SSc. Samples were also obtained from 12 healthy control subjects and 10 patients with scleroderma spectrum disorder (SSD) who did not fulfill the criteria for SSc but who had the potential to develop SSc. Mean serum leptin receptor levels were significantly higher in patients with SSD than in patients with SSc (255.7 ng/mL vs. 184.6 ng/mL, p < 0.05 according to a Mann-Whitney test). There were no statistically significant differences between healthy control subjects and patients with SSc. Clinical parameters were evaluated, and the frequency of esophageal reflux was significantly lower in patients with elevated serum leptin receptor levels than in those with reduced levels (6.3% vs. 35.3%, p < 0.05). In summary, these results suggest that the serum levels of leptin receptor are a clinically useful marker of SSD, and measurement of serum leptin receptor over time in patients with SSD may lead to early detection of SSc.
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PMID:Serum levels of leptin receptor in patients with systemic sclerosis. 2534 3