Biomedical subjects

Hidenobu Nagano

Publications and source records attributed to Hidenobu Nagano.

6 recordsLinked to original sources

PubMed2004

Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases.

Ecto-nucleotide pyrophosphatase/phosphodiesterase-I enzyme (E-NPP) consists of three closely related molecules: E-NPP1, E-NPP2 and E-NPP3. We investigated the expression and localization of E-NPP1 and -3 in human inflammatory and neoplastic bile duct diseases. Immunohistochemically E-NPP1 was located on the apical cytoplasmic side of cancer cells, whereas E-NPP3 was located in the apical plasma membrane. Western blot analysis revealed that the expression of E-NPP3, but not E-NPP1, was higher in tumor tissues than in surrounding tissues and the specific form of the E-NPP3 protein was readily detected in the sera of bile duct carcinoma (BDC) patients. Furthermore, it was confirmed that E-NPP3 was associated with migration ability by using of NIH3T3 cells that stably transfected with E-NPP3 cDNA. These results suggest that E-NPP3 is involved in the infiltration of neoplastic BDC and is possible to be a tumor marker.

Animals↗

PubMed2003

Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma.

SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 surgically excised human hepatocellular carcinoma (HCC) specimens. Both immunohistochemical and immunoblot analyses revealed that normal liver tissue, as well as tissue affected by chronic hepatitis or cirrhosis, contained substantial amounts of SAP-1. The expression level of SAP-1 in 75% of well-differentiated HCCs was similar to or higher than that observed in the surrounding noncancerous tissue. In contrast, the abundance of SAP-1 in 85.7% of moderately differentiated HCCs and in all poorly differentiated HCCs was greatly reduced compared with that in the adjacent tissue. Indeed, SAP-1 was almost undetectable in 83.3% of poorly differentiated HCCs. Furthermore, expression of recombinant SAP-1 in two highly motile human HCC cell lines resulted in a change in morphology and a marked reduction in both migratory activity and growth rate. In conclusion, these results indicate that SAP-1 expression is downregulated during the dedifferentiation of human HCC, and that this downregulation may play a causal role in disease progression.

Adult↗

PubMed2003

Hepatitis B virus DNA in anti-HBe-positive asymptomatic carriers.

OBJECTIVES: We examined the level of hepatitis B virus (HBV) DNA and the mutations in the precore, core and polymerase regions of HBV in sera from anti-HBe-positive asymptomatic carriers (ASC). METHODS: The amount of HBV DNA was determined semiquantitatively by mutation site-specific assay in sera from 19 anti-HBe-positive ASC and 31 HBeAg-positive patients with chronic liver disease (CLD). The mutations in the precore, core and polymerase (terminal protein) regions, spanning 1,037 nucleotides, of HBV in sera from three cases each of anti-HBe-positive ASC, HBeAg-positive ASC and HBeAg-positive CLD were examined by directly sequencing the amplified HBV DNA. RESULTS: The level of HBV viremia in anti-HBe-positive ASC was significantly lower than that in HBeAg-positive CLD patients (p < 0.01). By sequence analysis, there were a few missense mutations detected in HBeAg-positive ASC and HBeAg-positive CLD patients. In contrast, many mutations, especially in the central or N-terminal half of the core region and N-terminal part of the polymerase region, were detected in anti-HBe-positive ASC. CONCLUSION: Mutations not only in the precore/core region, but also in the polymerase region of HBV might cause damage to some important functions for efficient replication of HBV and be involved in the reduced amount of HBV in anti-HBe-positive ASC.

Adult↗

PubMed2003

Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.

Apoptosis↗

PubMed2003

A case of well-differentiated hepatocellular carcinoma arising in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic progressive, autoimmune liver disease that increases the risk of hepatobiliary malignancies at a late stage. We report a 66-year-old woman with PBC combined with hepatocellular carcinoma (HCC) accompanied by hypoglycemia. Two large tumors were detected on admission and the patient died because of tumor rupture and subsequent liver failure. Histological analysis revealed well-differentiated HCC in both of the tumors. Sometimes the patient had suffered from hypoglycemic attacks of unknown origin, but serum immunoreactive insulin (IRI) was within the normal range. It was interesting that such large well-differentiated hepatocellular carcinomas were generated in PBC.

Aged↗

PubMed2002

Histological grading and staging in chronic hepatitis: its practical correlation.

Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection or concomitant liver disease and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease.

Adult↗