Masami Kuniyoshi

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma.

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders.

Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells

Background: Recently, it has been reported that interleukin 4 (IL‐4) and 13 (IL‐13) directly activate fibroblasts and promote fibrosis. In the process of hepatic fibrosis, the effects of these cytokines on hepatic stellate cells (HSCs) are not well known.

ADIPOSE DIFFERENTIATION RELATED PROTEIN INDUCES LIPID ACCUMULATION AND LIPID DROPLET FORMATION IN HEPATIC STELLATE CELLS

SummaryThe function of adipose differentiation-related protein (ADRP) is known to be the uptake of long-chain fatty acids and formation of lipid droplets in lipid-accumulating cells. We hypothesized that ADRP might stimulate activated hepatic stellate cells (HSCs) to accumulate lipids, resulting in their transition to the quiescent state. In this study, cultured HSCs in fifth passages isolated from rat were infected by adenovirus vector expressing ADRP (Ad.GFP-ADRP), and morphologic and functional changes were evaluated in comparison with control HSCs infected by recombinant adenovirus-expressing β-galactosidase (Ad. LacZ). In Ad. GFP-ADRP-infected cells only, many tiny lipid droplets were apparent in the cytoplasm, while the outline of the cells was not changed. The ADRP was detected around the lipid droplets. In HSCs with intracellular actin filaments, the staining pattern of the filaments before and after infection with Ad.GFP-ADRP or Ad.LacZ did not differ. The cell proliferation rate was not influenced by infection with Ad.LacZ or Ad.GFP-ADRP. Type I collagen secretion from cells overexpressing ADRP was not significantly different from that of Ad.LacZ-infected cells. In our in vitro study, ADRP overexpression induced the formation of cytoplasmic lipid droplets in activated HSCs but could not convert other characteristics of the activated form into those of the quiescent form.

Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease

Abstract: 
Background: Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function.

Case report: RCAS1, a useful serum marker to predict the recurrence of cancer: Two cases of cholangiocarcinoma and pancreatic cancer

A tumor-associated antigen recognized by 22-1-1 antibody, which was established against the human uterine carcinoma cell line SiSo, was cloned as type II transmembrane protein and designated RCAS1 (1–3). As a result of functional in vitro assays, it has been suggested that the antigen can induce apoptosis on activated immune cells (1). RCAS1 expression has been immunohistochemically demonstrated in various kinds of cancer, and we also reported that the antigen was present in cancer cells of cholangiocarcinoma and pancreatic carcinoma (4, 5). Because RCAS1 also exists in soluble form, we developed an ELISA system to measure serum values of RCAS1 and reported that serum RCAS1 levels were elevated in patients with pancreaticobiliary cancers (5, 6). Therefore, we have suggested that serum RCAS1 is useful as a tumor marker for cancers of bile duct and pancreas and is able to predict relapse. We report here on two patients who had undergone curative operations for primary cancers, cholangiocarcinoma and pancreatic carcinoma, in whom RCAS1 was able to predict relapse several months before its actual detection.

Serum levels of HCV RNA and core protein before and after incubation at 37°C for 24 h

Abstract The kinetics of HCV during interferon (IFN) therapy have recently been described and the estimated virion half-life is an average of 2.7 h, suggesting that HCV infection is highly dynamic. The aim of this study was to evaluate serum levels of HCV-RNA and HCV core protein (HCV-Ag) before and after incubation at 37°C for 24 h. We also evaluated the viral kinetics during IFN treatment by determining their serum levels at 0, 24 and 48 h, and day 8 after the start of treatment. The decay slope was calculated as the logarithm of the ratio of HCV-RNA levels at 0 and 24 h of incubation: log(virus load) 24 h-log(virus load) 0 h and the estimated half-life was also calculated. The decay slope was −1.66±0.75 (−4.12 to −0.18) (mean±S.D. (range)) and the estimated virion half-life was 6.2±6.9 h (1.8–39.3). The HCV-RNA level was rapidly decreased to 6.8±13.1% of the initial load after incubation independently of the serotype. In contrast, the HCV-Ag level after incubation for 24 h was 98.7±12.2% of the initial level. The synthesized naked HCV-RNA (equivalent to 10 7 copy/ml) was not detected after 1-min incubation. These data suggested that HCV virions are very unstable and collapsed rapidly and that HCV-RNA, existing outside of virions, is immediately degraded in serum, whereas HCV-Ag remains stable. IFN treatment caused a rapid decrease in the levels of both HCV-RNA and HCV-Ag. The HCV-RNA decay slope was −1.95±0.96 (range: −3.48 to −0.50) and was similar to that seen in the incubation study. Our result suggested the significance of measuring HCV-Ag during clinical management independently of HCV-RNA, especially because of its high stability.

Clinical significance of urinary N1,N12-diacetylspermine levels in patients with hepatocellular carcinoma.

BACKGROUND/AIM N1,N12-diacetylspermine (DiAcSpm), a diacetylpolyamine which was recently identified in urine, appeared to be a useful tumor marker for urogenital cancers. Here we examined the clinical significance of urinary DiAcSpm as a tumor marker for hepatocellular carcinoma (HCC). METHODS Urine samples were collected from patients with HCC and benign liver diseases. Urinary levels of DiAcSpm were measured by ELISA, which was newly developed in order to analyze large numbers of samples. RESULTS The appropriate threshold value was set at 325 nM/g x creatinine. The sensitivity of the DiAcSpm assay for HCC was 65.5% and the specificity calculated between HCC and liver cirrhosis was 76.0%. The percentage of DiAcSpm-positive HCC patients was similar to that for AFP or PIVKA-II. At more advanced clinical stages, the positive percentage of these three markers increased but the DiAcSpm levels appeared to move independently of AFP and PIVKA-II. In HCC patients, the DiAcSpm levels reflected the progression of disease or the effect of treatment. CONCLUSIONS DiAcSpm levels were found to reflect the severity, activity or viability of HCC. Urinary DiAcSpm can therefore be considered one of the useful indexes for patients with HCC.

The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis

BACKGROUND Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis. METHODS Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment. RESULTS Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH. CONCLUSIONS We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.