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Biomedical subjects

Naoya Kato

Publications and source records attributed to Naoya Kato.

42 records · Page 3Linked to original sources
PubMed2002

Identification of genes associated with sensitivity to 5-fluorouracil and cisplatin in hepatoma cells.

BACKGROUND: The prognosis of patients with advanced hepatoma is grim. Although chemotherapy is adapted to such patients, the efficacy is low and the outcome cannot be predicted before therapy. In this study, we aimed to identify genes associated with sensitivity to 5-fluorouracil and cisplatin, drugs widely used in treatment, using gene expression profiles. METHODS: Gene expression was evaluated in eight human hepatoma cell lines using an in-house cDNA microarray including 2300 known genes. The 50% growth inhibitory concentrations (GI50) of 5-fluorouracil and cisplatin were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and designated as chemosensitivity. Genes with expression ratios associated with GI50 were selected using the permutation test. RESULTS: For 5-fluorouracil and cisplatin, 21 and 40 genes, respectively, were selected. From among the genes associated with 5-fluorouracil and cisplatin, several encoding metabolic enzymes were selected. In addition, several genes involved in the cell cycle and transcription were identified. CONCLUSIONS: We identified genes that may be associated with sensitivity to 5-fluorouracil and cisplatin. A list of these genes may be useful to elucidate how these drugs work on human hepatoma.

Carcinoma, Hepatocellular↗
PubMed2002

Analysis of the beta-catenin/T cell factor signaling pathway in 36 gastrointestinal and liver cancer cells.

We investigated the frequency and mechanism of beta-catenin/T cell factor (Tcf) signaling activation in a panel of 36 human gastrointestinal and liver cancer cell lines. Reporter assay and electrophoretic mobility shift assay revealed that the beta-catenin/Tcf signaling was upregulated in 12 of 12 (100%) colorectal, 5 of 8 (68%) gastric, 2 of 7 (29%) hepatic, and none of 9 pancreatic cancer cell lines. The activation of the pathway was mainly due to the mutation of adenomatous polyposis coli (APC) or beta-catenin, and Tcf-4 was highly expressed in these cell lines with upregulated signaling. Nuclear beta-catenin was observed not only in the signaling-activated cell lines, but also in 14 of 25 (56%) primary gastric cancers, 15 of 20 (75%) colon cancers, 5 of 19 (26%) hepatocellular carcinomas, and none of 13 pancreatic cancers. The presence of signaling-upregulated gastric cancer cell lines with intact APC and beta-catenin suggests the involvement of other mechanisms than mutations of APC or beta-catenin.

Carcinoma, Hepatocellular↗
PubMed2002

Novel nucleoside analogue MCC-478 (LY582563) is effective against wild-type or lamivudine-resistant hepatitis B virus.

The emergence of resistant hepatitis B virus (HBV) with the L528M mutation and/or the M552V and M552I mutations in the polymerase gene following long-term lamivudine treatment is becoming an important clinical problem. The aim of this study was to investigate the susceptibility of wild-type and lamivudine-resistant HBV to MCC-478 (LY582563), a novel nucleoside analogue derivative of phosphonomethoxyethyl purine. The susceptibility of wild-type HBV and lamivudine-resistant mutants (M552I, M552V, and L528M/M552V) to MCC-478 was examined by transient transfection of full-length HBV DNA into human hepatoma cells. HBV DNA replication was monitored by Southern blot hybridization, and the effective concentration required to reduce replication by 50% (EC(50)) was determined. The replicative intermediates of wild-type and lamivudine-resistant mutants were progressively diminished by treatment with increasing doses of MCC-478. The MCC-478 EC(50)s were 0.027 microM for wild-type HBV (about 20 times more efficient than lamivudine), 2.6 microM for M552I, 3.3 microM for M552V, and 2.0 microM for L528M/M552V. Wild-type HBV and lamivudine-resistant mutants are susceptible to MCC-478. MCC-478 appears to be a candidate for the treatment of HBV infection and exhibits potent activity against lamivudine-resistant HBV.

Antiviral Agents↗
PubMed2002

Weak association between SEN virus viremia and liver disease.

Recently, a novel DNA virus designated SEN virus (SEN-V), which is thought to be related to posttransfusion hepatitis, was discovered. The aim of the present study was to clarify the relationship between SEN-V infection and the development of liver disease. We examined SEN-V from the sera of 21 patients with non-B, non-C hepatocellular carcinoma (HCC) and 13 patients with non-B, non-C chronic liver disease (CLD) without HCC who were admitted to our hospital between 1995 and 1997. Thirty-two patients without liver disease served as controls and were also examined for SEN-V. SEN-V DNA was detected by the nested PCR method after extraction of DNA from serum. SEN-V DNA was detected in 74% (25 of 34) of patients with CLD with or without HCC who were negative for both hepatitis B virus surface antigen and anti-hepatitis C virus antibody. SEN-V DNA was detected in 69% (9 of 13) of CLD patients without HCC and in 76% (16 of 21) of HCC patients. The prevalence of SEN-V was no higher in patients with liver disease than in patients without liver disease (24 of 32; 75%). There were no significant differences in age, sex, liver function, history of blood transfusion, or amount of alcohol intake between SEN-V-positive and SEN-V-negative CLD and HCC patients. Genetic analysis suggested that SEN-V is closely related to the TT virus family. SEN-V was detected at almost the same frequency in patients with and without liver disease. SEN-V does not seem to contribute either to the pathogenesis of liver disease or to the development of HCC from chronic liver disease.

Aged↗
PubMed2001

Current Options for the Therapy of Chronic Hepatitis B Infection.

Until recently the only available treatment for chronic hepatitis B was interferon-alpha. Over the past few years a new class of antiviral has become available, the reverse transcriptase inhibitors. Lamivudine is a nucleoside analogue reverse transcriptase inhibitor that was recently approved in many countries for the treatment of hepatitis B. Despite the potent action of lamivudine, the development of new antivirals and new strategies to treat hepatitis B are still the major goal. We review the latest options for therapy of chronic hepatitis B, including combination strategies that could be an approach to improving the response rate of antivirals.

Journal Article↗