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Invasive ductal adenocarcinoma (IDA) of the pancreas (IDAP) originating from the ductal gland has a poor prognosis. Noninvasive carcinomas are principally intraductal papillary mucinous carcinomas (IPMCs) and pancreatic intraepithelial neoplasms 3 (PanIN-3). Small papillary-cohesive clusters, individually well-enveloped nuclei in well-preserved cytoplasm, centrally located nuclei, small nuclei (about 10 μm), euchromatin, clearly defined cell borders, small cytoplasm without prominent anisocytosis and no cytoplasm more than 21 μm in shortest diameter, a mixture of goblet cells, and a pleomorphic aspect are common in IPMC and intraductal papillary mucinous neoplasm (IPMN), whereas malignancy in nuclei are observed only in IPMC. PanIN-3 cells have small papillary-cohesive and compact clusters, a monomorphic aspect, and small dense cytoplasm and are highly suggestive of malignancy. IDA cells have loose sheet and solid clusters, poorly preserved cytoplasm, nuclei that tend to adhere to each other, large nuclei, a combination of large nuclei (short diameter <15 μm) with hyperchromatin, a monomorphic aspect, and abundant cytoplasm more than 21 μm in the shortest diameter. To preoperatively differentiate noninvasive IPMC and PanIN-3 from IDAP, these features would be clinically very useful. [ABSTRACT FROM AUTHOR]

Background High-mobility group box 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. The protein encoded by the box-A domain of the HMGB1 gene is known to act as a competitive inhibitor of HMGB1. In this study, we investigated whether box-A gene transfer results in box-A protein production in rats and assessed therapeutic efficacy in vivo using an acute liver failure (ALF) model. Materials and methods Three types of adenovirus vectors were constructed-a wild type and two mutants-and a mutant vector was then selected based on the secretion from HeLa cells. The secreted protein was subjected to a tumor necrosis factor (TNF) production inhibition test in vitro. The vector was injected via the portal vein in healthy Wistar rats to confirm box-A protein production in the liver. The vector was then injected via the portal vein in rats with ALF. Results Western blot analysis showed enhanced expression of box-A protein in HeLa cells transfected with one of the mutant vectors. The culture supernatant from HeLa cells transfected with the vector inhibited TNF-α production from macrophages. Expression of box-A protein was confirmed in the transfected liver at 72 h after transfection. Transfected rats showed decreased hepatic enzymes, plasma HMGB1, and hepatic TNF-α messenger RNA levels, and histologic findings and survival were significantly improved. Conclusions HMGB1 box-A gene transfer results in box-A protein production in the liver and appears to have a beneficial effect on ALF in rats. [ABSTRACT FROM AUTHOR]