Hedgehog Signaling Modulates Interleukinâ 33â Dependent Extrahepatic Bile Duct Cell Proliferation in Mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147852/1/hep41295_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147852/2/hep41295.pd

Essential role of gastric gland mucin in preventing gastric cancer in mice

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第916号）・唐澤文寿Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc). Previously, we identified human alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT), which is responsible for the O-glycan biosynthesis and characterized alpha GlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of alpha GlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced alpha GlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of alpha GlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, alpha GlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.ArticleJOURNAL OF CLINICAL INVESTIGATION. 122(3):923-934 (2012)journal articl

Significance of serum palmitoleic acid levels in inflammatory bowel disease

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD

Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?

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Characteristics and Risk Factors of Delayed Perforation in Endoscopic Submucosal Dissection for Early Gastric Cancer

(1) Background: Delayed perforation after gastric endoscopic submucosal dissection (ESD) for early gastric cancer is a relatively uncommon and serious complication that sometimes requires emergency surgery. This study aimed to determine the clinicopathological features, risk factors, and appropriate management strategies for delayed perforation. (2) Methods: This study included 735 patients with 791 lesions who underwent ESD for early gastric cancer at a single institution between July 2009 and June 2019. We retrospectively compared the clinical features of patients with and without delayed perforations. (3) Results: The incidence of delayed perforations was 0.91%. The identified risk factors included a postoperative stomach condition and histopathological ulceration. A comparison between delayed and intraoperative perforations revealed a postoperative stomach condition as a characteristic risk factor for delayed perforation. Patients with delayed perforation who avoided emergency surgery tended to exhibit an earlier onset of symptoms such as abdominal pain and fever. No peritoneal seeding following delayed perforation was observed for any patient. (4) Conclusions: A postoperative stomach condition and histopathological ulceration were risk factors for delayed perforation. Delayed perforation is a significant complication that requires careful monitoring after gastric ESD for early gastric cancer, particularly in patients with postoperative gastric conditions

Magnifying Endoscopic Findings Can Predict Clinical Outcome during Long-Term Follow-Up of More Than 12 Months in Patients with Ulcerative Colitis

Background and Aims. To explore the association of magnifying endoscopic (ME) findings with histopathology and relapse in ulcerative colitis (UC). Methods. Forty-six patients with UC underwent ME with narrow band imaging (NBI) and crystal violet staining and were followed for more than 12 months. ME findings with vital staining were classified into ME-A, regular arrangement of round to oval pits; ME-B, irregular arrangement with/without enlarged spaces between even pits; ME-C, irregular pits in size and shape with more irregular arrangement of pits; and ME-D, disrupted or disappeared pits. NBI-guided ME features of microvascular pattern (MVP) were divided into the MVP-regular and MVP-irregular type. Results. There were 5, 24, 10, and 7 cases of ME-A, ME-B, ME-C, and ME-D grade, respectively, while there were 21 and 25 of MVP-regular and MVP-irregular type, respectively. ME classifications were significantly associated with Matts endoscopic grade. ME classifications and MVP types were significantly associated with each pathognomonic microscopic feature of severe mucosal inflammation, crypt abscess, and goblet cell depletion. There were significant differences in the percentages of remission among ME classifications and between MVP types. Conclusion. ME findings can be predictive of relapse in UC and reliable for in vivo histopathological assessment