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Song H.J.,Asan Digestive Disease Research Institute | Song H.J.,Asan Medical Center | Myung S.-J.,Asan Digestive Disease Research Institute | Myung S.-J.,Asan Medical Center | And 14 more authors.
Cancer Investigation

We investigated the tumor suppressor activity and regulatory mechanism of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer; 15-PGDH expression was lost in 70.1% of malignant human gastric tissues, but was preserved in normal and metaplastic gastritis. KATO III and SNU-719 cells were transfected with pcDNA3.1-empty vector or an expression vector encoding wild-type 15-PGDH. In TUNEL assays apoptotic cell numbers were increased in KATO-PGDH-WT cells compared with control. We found that EGFR and ERK1/2 inhibitors clearly increased the expression of 15-PGDH in KATO III cells. Our findings demonstrate both downregulation and a tumor suppressor activity of 15-PGDH in gastric cancer. Copyright © 2011 Informa Healthcare USA, Inc. Source

Song H.J.,Asan Digestive Disease Research Institute | Jang S.J.,Asan Digestive Disease Research Institute | Yun S.-C.,University of Ulsan | Lee S.-M.,Asan Digestive Disease Research Institute | And 3 more authors.
Gut and Liver

Background/Aims: The levels of pepsinogen (PG) I and the PGI/II ratio are useful serologic markers for chronic atrophic gastritis. This study evaluated the performance and clinical implications of these markers in patients undergoing endoscopic mucosectomy. Methods: We enrolled 142 consecutive patients with early gastric tumors and Helicobacter pylori infection who were eligible for mucosectomy. Chronic gastritis and atrophy were assessed using four defined biopsy procedures. Serum PGs were measured by an enzyme immunoassay. Optimal diagnostic cut-offs and performance were determined using receiver operating characteristic curves. Results: The PGI level and the PGI/II ratio decreased with corpus-dominant gastritis and as atrophy advanced toward the corpus greater curvature (GC). For the presence of corpus GC atrophy, the areas under the PGI and PGI/II-ratio curves were 0.82 and 0.77, respectively. The optimal cut-off levels were 59.3μg/L for PGI (sensitivity, 83.3%; specificity, 78.4%) and 3.6μg/L for PGI/II ratio (sensitivity, 70.0%; specificity, 78.4%). Using these serologic cut-off levels, we found that the frequency of corpus tumor location differed significantly (32.9% vs 11.1% for PGI <59.3 and =59.3μg/L, respectively; and 31.1% vs 14.8% for PGI/II ratio <3.5 and ≥3.5, respectively; p<0.05). Conclusions: A low PGI level and PGI/II ratio are valuable serologic markers for predicting corpus GC atrophy, and have clinical implications with respect to the corpus location of tumors in mucosectomy patients. Source

Do Y.S.,Asan Digestive Disease Research Institute | Myung S.-J.,Asan Digestive Disease Research Institute | Kwak S.-Y.,University of Ulsan | Cho S.,University of Ulsan | And 5 more authors.
Journal of Neurogastroenterology and Motility

Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a disorder characterized by recurrent symptoms suggestive of obstruction such as abdominal pain, proximal distension with extremely suppressed motility in the absence of lumen-occluding lesion, whose etiology/ pathophysiology is poorly understood. In this study we investigated a functionally obstructive lesion that could underlie symptoms of CIPO. Methods We studied colons surgically removed from 13 patients exhibiting clinical/pathological features of pseudo-obstruction but were unresponsive to standard medical treatments. The colons were characterized morphologically, functionally and molecularly, which were compared between regions and to 28 region-matched controls obtained from colon cancer patients. Results The colons with pseudo-obstruction exhibited persistent luminal distension proximally, where the smooth muscle was hypertrophied with changes in the cell phenotypes. Distinct luminal narrowing was observed near the distal end of the dilated region, close to the splenic flexure, previously referred to as the "transition zone (TZ)" between the dilated and non-dilated loops. Circular muscles from the TZ responded less to depolarization and cholinergic stimulation, which was associated with downregulation of L-type calcium channel expression. Smooth muscle contractile protein was also downregulated. Myenteric ganglia and neuronal nitric oxide synthase (nNOS) positive cells were deficient, more severely in the TZ region. Interstitial cells of Cajal was relatively less affected. Conclusions The TZ may be the principal site of functional obstruction, leading to proximal distension and smooth muscle hypertrophy, in which partial nNOS depletion could play a key role. The neuromuscular abnormalities probably synergistically contributed to the extremely suppressed motility observed in the colonic pseudo-obstruction. © 2015 The Korean Society of Neurogastroenterology and Motility. Source

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