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Goshi Shiota

Publications and source records attributed to Goshi Shiota.

36 records · Page 2Linked to original sources
PubMed2004

Retinoic acid receptor alpha dominant negative form causes steatohepatitis and liver tumors in transgenic mice.

Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Adenoviral-mediated HGF expression inhibits germ cell apoptosis in rats with cryptorchidism.

BACKGROUND: Prior studies have shown that the hepatocyte growth factor (HGF), as known for its multiple biological effects, possibly regulates spermatogenesis or tubulogenesis in the testis. To clarify the effect of HGF on restoration of spermatogenesis, or testicular weight, we transferred the HGF gene into the testis of the rat experimental cryptorchid model. METHODS: Replication-deficient recombinant adenoviral vectors containing the CAG promoter driving rat HGF (pAxCAHGF) and LacZ (pAxCALacZ) were constructed. Sprague-Dawley rats surgically induced with unilateral cryptorchidism and subsequent orchidopexy were divided into three groups: control (PBS), pAxCALacZ and pAxCAHGF by intratesticular injection. At 2 and 4 weeks after subsequent orchidopexy, testes were removed and weighed. These specimens were analyzed histopathologically, and examined for cell apoptosis. HGF expression in these specimens associated with c-Met receptor-mediated signal molecules was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot or immunohistochemical study. RESULTS: Adenovirus-mediated HGF gene transfer induced overexpression of HGF in some seminiferous epithelial cells and interstitial cells, increased the phosphorylation of ERK and Akt, and decreased numbers of apoptotic cells of germ cells. HGF transduction also significantly increased the numbers of germ cells and testicular weight by 4 weeks compared with the other control groups. CONCLUSIONS: Adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored spermatogenesis.

Adenoviridae↗
PubMed2004

Soluble c-kit receptor mobilizes hematopoietic stem cells to peripheral blood in mice.

OBJECTIVE: The mechanisms of mobilization of hematopoietic stem cells (HSC) from bone marrow to peripheral blood (PB) by cytokines are poorly understood. One hypothesis is that cytokines disrupt cytoadhesive interactions of stem cells with bone marrow stroma. The soluble portion of c-kit (s-kit) binds stem cell factor (SCF) and can specifically block the ability of SCF to bind HSC. MATERIALS AND METHODS: To examine stem cell mobilization by s-kit, we prepared PB mononuclear cells from s-kit- or granulocyte colony-stimulating factor (G-CSF)-treated mice and assayed their colony-forming abilities and their long-term reconstituting abilities by transplantation into lethally irradiated Ly-5.2 congenic mice. RESULTS: We confirmed the published findings that human recombinant s-kit can block SCF-stimulated hematopoietic colony growing. We then found that s-kit could mobilize colony-forming cells from bone marrow to PB, and we found long-term reconstitution cells in the PB from s-kit-treated mice. The majority of s-kit-mobilized stem cells were in the CD34(+) cell population. We also tested the additive effect between G-CSF and s-kit. The mean percentages of donor cells in the mice transplanted with Lin(-) cells from the G-CSF-treated mice and the G-CSF/s-kit-treated mice were 44.6% and 64.8%, respectively (p=0.028). CONCLUSIONS: These findings demonstrate that stem cells with long-term engraftment capabilities can be mobilized by s-kit, and that s-kit combined with G-CSF treatment leads to significant enhancement of engraftment efficiency, suggesting mobilization via disruption between c-kit and SCF as the mechanism.

Animals↗
PubMed2004

State-dependent blocking actions of azimilide dihydrochlo-ride (NE-10064) on human cardiac Na(+) channels.

BACKGROUND: Azimilide reportedly blocks Na(+) channels, although its mechanism remains unclear. METHODS AND RESULTS: The kinetic properties of the azimilide block of the wild-type human Na(+) channels (WT: hH1) and mutant DeltaKPQ Na(+) channels (DeltaKPQ) expressed in COS7 cells were investigated using the whole-cell patch clamp technique and a Markovian state model. Azimilide induced tonic block of WT currents by shifting the h infinity curve in the hyperpolarizing direction and caused phasic block of WT currents with intermediate recovery time constant. The peak and steady-state DeltaKPQ currents were blocked by azimilide, although with only a slight shift in the h infinity curve. The phasic block of peak and steady-state DeltaKPQ currents by azimilide was significantly larger than the blocking of the peak WT current. The affinity of azimilide predicted by a Markovian state model was higher for both the activated state (Kd(A) =1.4 micromol/L), and the inactivated state (Kd(I) =1.4 micromol/L), of WT Na(+) channels than that for the resting state (Kd(R) =102.6 micromol/L). CONCLUSIONS: These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states.

Dose-Response Relationship, Drug↗
PubMed2004

Developmental changes of Ni(2+) sensitivity and automaticity in Nkx2.5-positive cardiac precursor cells from murine embryonic stem cell.

BACKGROUND: It is controversial which subtypes of T type Ca(2+) channels are implicated in automaticity of cardiac cells during the embryonic period. METHOD AND RESULTS: The effect of Ni(2+) on the automaticity of Nkx2.5-positive cardiac precursor cells sorted from embryonic stem cells during their differentiation was examined using patch clamp techniques. Although 40 micromol/L Ni(2+), which is enough to block Ni(2+)sensitive T type-Ca(2+) channels, decreased the spontaneous beating rate in all cells in the early and intermediate stage, Ni(2+) did not show any effects on the automaticity of 50% of the cells in the late stage. CONCLUSION: These results indicate that Ni(2+)-sensitive T-type Ca(2+) channels expressed in the Nkx2.5-positive cardiac precursor cells are developmentally regulated.

Animals↗
PubMed2003

Expression of Fhit, Mlh1, and P53 protein in human gallbladder carcinoma.

There is limited information on the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). The Fragile Histidine Triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in a variety of human malignancies. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins. We analyzed Fhit and Mlh1 protein expressions using immunohistochemical methods in 20 GBCs and three gallbladder adenomas (GBAs) to elucidate the role of Fhit protein in gallbladder carcinogenesis. In addition, we examined whether Fhit and Mlh1 protein expressions correlated with P53 expression and clinicopathological findings. Significant loss or reduction in Fhit expression was noted in nine (45%) of the GBCs and one of the GBAs. Loss of Mlh1 protein expression was detected in six (30%) of the GBCs and one of the GBAs. Reduced Fhit expression was significantly associated with the absence of Mlh1 protein expression in the GBCs and the GBAs (p=0.0186). P53 overexpression was present in 11 (55%) of the GBCs, but none of the GBAs. Fhit and Mlh1 protein expressions were not significantly associated with P53 expression and clinicopathological findings. These results suggested that reduced Fhit expression might be involved in the development of GBC and be correlated with Mlh1 expression.

Acid Anhydride Hydrolases↗
PubMed2003

Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway.

Hepatocyte growth factor (HGF) is a potent mitogen for a variety of cells including hepatocytes. While rat oval cells are supposed to be one of hepatic stem cells, biological effects of HGF on oval cells and their relevant signal transduction pathways remain to be determined. We sought to investigate them on OC/CDE22 rat oval cells, which are established from the liver of rats fed a choline-deficient/DL-ethionine-supplemented diet. The oval cells were cultured on fibronectin-coated dishes and stimulated with recombinant HGF, transforming growth factor-alpha (TGF-alpha), and thrombopoietin (TPO) under the serum-free medium condition. HGF treatment enhanced [3H]thymidine incorporation into oval cells in a dose-dependent manner. On the contrary, treatment with TGF-alpha or TPO had no significant effects on [3H]thymidine incorporation into the oval cells. c-Met protein was phosphorylated at the tyrosine residues after the HGF treatment. AKT, extracellular signal-regulated kinase 1/2 (ERK1/2), and p70(s6k) were simultaneously activated after the HGF stimulation, peaking at 30min after the treatment. The activation of AKT, p70(s6k), and ERK1/2 induced by HGF was abolished by pre-treatment with LY294002, a phosphoinositide 3-OH kinase (PI3K) inhibitor, and U0126, a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor, respectively. When the cells were pre-treated with LY294002 prior to the HGF stimulation, the proliferative action of HGF was completely abrogated, implying that the PI3K/AKT signaling pathway is responsible for the biological effect of HGF. These in vitro data indicate that HGF exerts a proliferative action on hepatic oval cells via activation of the PI3K/AKT signaling pathway.

Cell Division↗
PubMed2003

Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion.

Despite the heteroplasmic lower population of mitochondrial (mt) DNA deletion, mtDNA deletion is significantly related to the loss of atrial adenine nucleotides. To elucidate its mechanism, we examined the frequency of a 7.4-kb mtDNA deletion, the concentration of adenine nucleotides, and the activity of AMP catabolic enzymes in 10 human right atria obtained from cardiac surgery, using quantitative PCR, HPLC, and immunoprecipitations. The atrial concentrations of ATP, ADP, AMP, and the total adenine nucleotides were significantly lower in patients with deletion than those in patients without deletion, despite the lower frequency of their deletion. The activities of total AMP deaminase (AMPD), liver-type (AMPD 2), and heart-type isoform (AMPD 3) were significantly higher in patients with deletion than in patients without deletion, although there was no significant difference in the cytosolic 5(')-nucleotidase among them. In conclusion, mtDNA deletion coordinately induces AMP deaminase to contribute to the loss of atrial adenine nucleotides through degrading AMP excessively.

AMP Deaminase↗
PubMed2003

Expression of 8-hydroxy-2'-deoxyguanosine in chronic liver disease and hepatocellular carcinoma.

Reactive oxygen species may be involved in the progression of chronic liver disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether clinicopathological findings in liver diseases are related to oxidative DNA damage, hepatic expression of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) was examined in 75 liver disease patients, which included 32 chronic hepatitis (CH), 13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8-OHdG-positive hepatocytes than LC (P < 0.05). In CH and LC, the number of 8-OHdG-positive hepatocytes was correlated with alanine aminotransferase and asparate aminotransferase (P < 0.01 and P < 0.05, respectively). Of 30 HCC cases, 25 cases (83%) showed stronger immunoreactivity than non-cancerous counterparts. The patients with poorly differentiated HCC had a larger tumor size and higher levels of AFP, and exhibited higher labeling indices of PCNA-, TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated HCC. Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic liver disease and determination of 8-OHdG is useful in assessing high-grade malignancy in HCC.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Transgene-derived hepatocyte growth factor attenuates reactive renal fibrosis in aristolochic acid nephrotoxicity.

BACKGROUND: Hepatocyte growth factor (HGF) has been demonstrated to attenuate acute tubular necrosis and interstitial fibrosis in a variety of rodent models of kidney disease. We investigated how HGF could affect chronic toxic nephropathy/interstitial fibrosis caused by aristolochic acid (AA). METHODS: Wild-type and HGF transgenic mice received daily intraperitoneal injections of AA for 14 days. At sacrifice, kidneys were removed and used for microscopy examination and in vitro studies. To determine the molecular mechanisms of anti-fibrotic effects of HGF, cultured murine tubular epithelial cells (mProx24) were employed. RESULTS: Significant tubular degeneration was observed in both the transgenic and the wild-type mice to the same degree after 2 weeks treatment with AA. Interstitial fibrosis subsequently developed in the wild-type mice 4 weeks after cessation of AA administration. However, the transgenic mice manifested less fibrotic changes. Decreased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased matrix metalloproteinase-9 activity could partially account for the attenuation of fibrogenesis in the transgenic mouse kidney. HGF at 10 and 100 ng/ml could block TIMP-1 gene expression in mProx24 induced by epidermal growth factor, but a decrease in the number of mProx24 via apoptosis induced by AA was blocked only by HGF at 100 ng/ml. CONCLUSION: Circulating transgene-derived HGF (2-10 ng/ml) could not prevent tubular degeneration caused by AA, but attenuated interstitial fibrogenesis during tubular regeneration. These findings suggest a possible therapeutic efficacy for renal interstitial fibrosis following tubular degeneration even of low-dose HGF.

Animals↗
PubMed2002

Synergistic effects of (-)-epigallocatechin gallate with sulindac against colon carcinogenesis of rats treated with azoxymethane.

(-)-Epigallocatechin gallate (EGCG), a major constituent of green tea, has been shown to exhibit anti-cancer activity. Sulindac is also well known as a cancer-preventive agent against colon cancer, but its usage is restricted because of its adverse effects, as exemplified by gastrointestinal bleeding. In the present study, we examined whether a combination of EGCG and sulindac shows synergistic effects for cancer-preventive activity for rat colon carcinogenesis induced by azoxymethane (AOM); we examined the number of aberrant crypt foci (ACF) representing preneoplastic lesions, the argyrophilic nucleolar organizer region (AgNOR) as an indicator of cell proliferation, and the incidence of apoptosis. The AOM treatment induced an average of 46.2+/-4.9 ACF/colon, and sulindac and EGCG significantly reduced the incidence of ACF/colon to 21.4+/-3.4 and 19.5+/-5.8, respectively (P<0.01). The co-treatment with EGCG and sulindac resulted in significantly reduced ACF formation (10.0+/-3.2; P<0.01). The results of the AgNOR analysis indicated that the treatment with EGCG and/or sulindac suppressed AOM-induced cell proliferation. The present results also revealed that the combination of EGCG and sulindac synergistically enhanced apoptosis significantly (P<0.01). Thus, our findings suggest that EGCG with sulindac synergistically suppresses ACF formation by enhancing apoptosis and, therefore, that EGCG is a suitable candidate for use in combination with cancer-preventive agents, such as sulindac, to reduce their adverse effects.

Animals↗
PubMed2002

Effects of cyclooxygenase-2 inhibitor NS-398 on APC and c-myc expression in rat colon carcinogenesis induced by azoxymethane.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to protect against the development of colon cancer; however, the mechanism(s) by which NSAIDs exert their effects is still unclear. The aim of this study was to examine the effects of NSAIDs on the expression of the tumor suppressor APC gene and the c-myc oncogene in the colons of rats treated with a colon-specific carcinogen, azoxymethane (AOM). METHODS: Gene expression levels were estimated by a reverse transcription (RT)-competitive polymerase chain reaction (PCR) method. RESULTS: The group of rats simultaneously administered AOM and NS-398, a cyclooxygenase (COX)-2 inhibitor, showed a significant reduction in the number of preneoplastic lesions of colon cancer compared with that in the group of rats treated with AOM alone. Furthermore, the APC expression level in the group of rats treated with both AOM and NS-398 was significantly greater than that in the group of rats treated with AOM alone; this result for APC gene expression was reconfirmed by the immunohistochemical staining of APC protein. In addition, c-myc mRNA expression was clearly decreased in the group of rats treated with both AOM and NS-398 compared with the level in the group of rats treated with AOM alone. CONCLUSIONS: Our data thus indicate that NS-398 causes an increase in APC expression and a decrease in c-myc expression.

Animals↗
PubMed2002

A case with hepatic fibrosis showing ascites and esophageal varices induced by oral UFT(R) administration.

An 81-year-old male patient developed hepatic fibrosis with ascites and esophageal varices 4 years after oral administration of UFT(R) as postoperative adjuvant therapy for lung cancer. Although serum transaminase levels remained normal during follow-up periods, ascites developed 3 years after the treatment, and disappeared rapidly after the cessation of UFT(R), but recurred by accidental readministration of UFT(R). Serum markers for hepatitis viruses, various auto antibodies and a history of alcoholic abuse were all negative. Liver biopsy showed mild to moderate hepatic fibrosis without hepatocellular necrosis. Serum levels of N-terminal propeptide of type III procollagen, 7S fragment of type IV collagen and hyaluronic acid were elevated at diagnosis and decreased after the discontinuation of UFT(R). Esophageal varices were also improved. These findings suggest that hepatic fibrosis can be induced by oral administration of UFT(R) and that serum fibrogenesis/fibrosis markers are useful for early diagnosis of UFT(R)-induced hepatic fibrosis.

Journal Article↗
PubMed2002

Effects of Sho-Saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine formation.

Oxidative stress plays an important role in hepatocarcinogenesis. Although Sho-saiko-to (TJ-9), a Japanese herbal medicine which has been recently administered to patients with chronic liver disease in Japan, prevents hepatocarcinogenesis, the mechanism by which TJ-9 protects against cancer development is not fully understood. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a DNA adduct by reactive oxygen species, is known as a parameter of genetic risk for hepatocarcinogenesis. To clarify whether the preventive effect on hepatocarcinogenesis by TJ-9 is dependent on 8-OHdG, the effect on 8-OHdG levels by TJ-9 was examined by using high-performance liquid chromatography-mass spectrometry (LC-MS) in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model of male Fisher rats. TJ-9 reduced the number of preneoplastic cells, detected as the glutathione S transferase P (GST-P)-positive hepatocytes, and inhibited the development of liver tumors. TJ-9 also significantly decreased the formation of 8-OHdG, as indicated by LC-MS and immunohistochemical analysis. In addition, ornithine decarboxylase (ODC) activity and the number of proliferating cell nuclear antigen (PCNA)-positive cells were not altered. An electron paramagnetic resonance spin-trapping technique showed that TJ-9 scavenges hydroxyl radicals in a dose-dependent manner. In conclusion, the results of the present study suggest that TJ-9 prevents hepatocarcinogenesis in association with inhibition of 8-OHdG formation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats.

Ursodeoxycholic acid (UDCA) is used worldwide for treatment of primary biliary cirrhosis and chronic liver diseases. However, its action on hepatocarcinogenesis remains to be explored. To clarify its effect, in vivo and in vitro experiments were performed. Ninety Fisher 344 rats were fed a standard diet (Group 1, n = 30), a standard diet supplemented with 0.1% UDCA (Group 2, n = 30) and 0.3% UDCA (Group 3, n = 30). The rats were given an i.p. injection of diethylnitrosamine (DEN) weekly for 6 weeks. Fifteen additional rats were fed 0.3% UDCA supplemented diet without DEN treatment (Group 4). The rats were killed at 5, 10 and 18 weeks after the last injection of DEN. The number of liver tumor and percentage of the GST-P-positive hepatocytes were significantly reduced by UDCA treatment. The PCNA-positive cells were decreased by administration of UDCA at 18 weeks. The increased number of apoptotic cells was observed in the GST-P-negative area at 5, 10 and 18 weeks and in the GST-P-positive area at 18 weeks in the UDCA group. Expression of Bax in mitochondria and cytochrome c in cytosol was increased by UDCA treatment. Caspase 3 activity was also increased in the UDCA groups. The addition of UDCA into the culture of Huh7 and Fao hepatocellular carcinoma (HCC) cells induced apoptosis in a dose-dependent manner. The data of the present study suggest that UDCA treatment reduces hepatocarcinogenesis via inducing apoptosis of 'initiated hepatocytes' as well as inhibiting proliferation.

Animals↗
PubMed2002

Induction of hepatocyte growth factor in stromal cells by tumor-derived basic fibroblast growth factor enhances growth and invasion of endometrial cancer.

Tumor progression is often regulated through interactions between carcinoma cells and host stromal cells. In this study of endometrial cancer, we investigated one mechanism potentially involved in hepatocyte growth factor (HGF)-mediated cancer-stromal interactions. Endometrial cancer cells (HEC-1 and ISHIKAWA) expressed the c-met receptor, but HGF did not. HGF, however, did stimulate the proliferation and invasion of these cells. The HGF gene was expressed in stromal cells, which had been separated from primary cultures of endometrial cancers, 6.4 times more than in isolated normal endometrial stromal cells. Immunohistochemical staining revealed immunoreactive HGF in cancer stromal cells, the staining intensity being more pronounced in cancer tissue than in normal endometrium. The conditioned medium from normal epithelial cells and cancer cell lines induced HGF production in normal stromal cells. We identified basic fibroblast growth factor as an HGF inducer derived from endometrial cancer cell lines. Basic fibroblast growth factor derived from tumor cells may induce HGF in endometrial stromal cells, whereas stromal cell-derived HGF leads to the invasive growth of carcinoma cells. These interactions, mediated by HGF and HGF inducers, may play a significant role in the progression of endometrial cancer.

Cell Division↗
PubMedDate not supplied

Serum levels of interleukin-10, interleukin-12 and soluble interleukin-2 receptor in chronic liver disease type C.

BACKGROUND/AIMS: It is still unclear whether and how Th1/Th2 type cytokines are involved in the progression of chronic liver disease type C. We therefore examined serum levels of IL-10, IL-12 and sIL-2R (soluble IL-2 receptor) in association with clinical parameters in chronic liver disease type C, whereas IL-12 and sIL-2R represent Th1 cytokine and IL-10 does Th2 cytokine, respectively. METHODOLOGY: Serum levels of IL-10, IL-12 and sIL-2R were measured in 110 patients, including 36 with chronic hepatitis, 24 with liver cirrhosis and 50 with hepatocellular carcinoma in comparison with 19 normal individuals, by an enzyme-linked immunosorbent assay. In 9 chronic hepatitis patients, serum levels of these cytokines were measured before and after interferon therapy. In 28 with hepatocellular carcinoma, they were also measured before and after transcatheter arterial embolization. RESULTS: Serum levels of IL-10 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 3.9 +/- 1.8 pg/mL, 5.7 +/- 6.4 pg/mL and 5.6 +/- 8.9 pg/mL, respectively. IL-10 level was significantly correlated with level of y-globulin. Serum levels of IL-12 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 347.4 +/- 150.3 pg/mL, 365.2 +/- 130.7 pg/mL and 399.4 +/- 258.2 pg/mL. sIL-2R levels in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 614.6 +/- 223.5 U/mL, 878.7 +/- 330.5 U/mL and 1037.9 +/- 412.0 U/mL. Serum levels of IL-12 and sIL-2R were significantly elevated on day 7 after interferon therapy compared to day 0 (p < 0.05 and p < 0.001, respectively), while no significant difference was seen in IL-10. Serum level of IL-10 was significantly elevated on day 3, and that of sIL-2R was elevated on day 3 and 7 after transcatheter arterial embolization, while that of IL-12 was decreased on day 3 and 7. CONCLUSIONS: The results of the present study suggest that Th1/Th2 type cytokines are changed in association with progression of chronic liver disease type C and in response to therapy.

Aged↗