The core 3 structure of the O-glycan, GlcNAc␤1-3GalNAc␣1-Ser͞ Thr, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by ␤1,3-N-acetylglucosaminyltransferase 6 (␤3Gn-T6; core 3 synthase). We generated an anti-␤3Gn-T6 mAb (G8-144 mAb) and performed immunohistochemical analyses. In normal stomach and colon, ␤3Gn-T6 was strongly expressed in the Golgi region of epithelia. In contrast, its expression was markedly down-regulated in gastric and colorectal carcinomas. Tissue specimens from a familial adenomatous polyposis patient showed a clear correlation between the down-regulation of ␤3Gn-T6 expression and the degree of dysplasia͞neoplasia. In vitro, the level of ␤3Gn-T6 transcript was increased according to the differentiation of Caco-2 cells. These results suggested that the expression of ␤3Gn-T6 is closely regulated during differentiation and dedifferentiation. ␤3Gn-T6 would be a useful marker for distinguishing between benign adenomas and premalignant lesions. HT1080 FP-10 cells stably transfected with the ␤3Gn-T6 gene showed a decrease in the core 1 structure, Gal␤1,3GalNAc␣1-Ser͞ Thr, probably due to competition between the core 1 synthase and core 3 synthase. The migration activity of the transfectants was markedly lower than that of mock transfectants in vitro, and lung metastasis after i.v. injection of the transfectants into nude mice was significantly suppressed. These findings indicated that the core structures of O-glycans are profoundly involved in the metastatic capacity of cancer cells.glycosyltransferase ͉ stomach ͉ familial adenomatous polyposis ͉ immunohistochemical analysis

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With careful patient selection, radical resection for gallbladder cancer improves the prognosis with acceptable operative mortality and morbidity rates, even for stage IV disease, provided that complete gross tumour resection is combined with radiotherapy.

Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin. We have identified in A. actinomycetemcomitansY4 a cluster of genes encoding a cytolethal distending toxin (CDT). This new member of the CDT family is similar to the CDT produced byHaemophilus ducreyi. The CDT from A. actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G2/M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. The three proteins, CDTA, -B and -C, encoded by thecdt locus were all required for toxin activity. Antiserum raised against recombinant CDTC completely inhibited the cytotoxic activity of culture supernatant and cell homogenate fractions ofA. actinomycetemcomitans Y4. These results strongly suggest that the CDT is responsible for the cytotoxic activity present in the culture supernatant and cell homogenate fractions of A. actinomycetemcomitans Y4. This CDT is a new putative virulence factor of A. actinomycetemcomitans and may play a role in the pathogenesis of periodontal diseases.

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This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.

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Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC-specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA-captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n 5 30) and benign diseases (n 5 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity 5 90.0%, specificity 5 76.3%, and area under the curve 5 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported. Conclusion: Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores. (HEPATOLOGY 2010;52:174-182) C holangiocarcinoma (CC) is an aggressive malignant tumor arising from the epithelial lining of the intrahepatic biliary tract. Although it contributes to only 15% of the total incidence of primary liver cancer, 1 recent epidemiological reports show that the CC incidence has increased significantly in Abbreviations: AFP, alpha-fetoprotein; AUC, area under the curve; BDE, bile duct epithelia; BSA, bovine serum albumin; CA19-9, carbohydrate antigen 19-9;