Fumitoshi Karasawa

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

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc 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 αGlcNAc 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 αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.

Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases

IntroductionAnorectal malignant melanoma (AMM) is a relatively rare disease. Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine. In this paper, we report five cases of AMM that have been treated by surgery and/or other methods at Shinshu University Hospital within the last decade. We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM.Results and discussionAmong our AMM patients, two who underwent radical abdominoperineal resection had long survival, while the other three patients who underwent palliative surgery had a poor outcome. On the total of 79 AMM patients, those who underwent curative surgery had a better outcome than those who underwent palliative surgery (p < 0.0001). Furthermore, the outcome of AMM patients at stages 0 and I was better than that of AMM patients at stages II, III, and IV (p < 0.0001). There was no significant difference in survival between AMM patients with and without adjuvant chemotherapy.ConclusionIn conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.