PubMed Health⌕ Search

Biomedical subjects

Michio Sata

Publications and source records attributed to Michio Sata.

At least 19 recordsLinked to original sources
PubMed2007

Impaired filterability of erythrocytes from patients with chronic hepatitis C and effects of eicosapentaenoic acid on the filterability.

Although erythrocyte filterability plays a key role in microcirculation, it is unknown whether the filterability of erythrocytes from patients with chronic hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte filterability in CH-C patients in relation to medical treatment. The mean erythrocyte filterability (%) for all 24 patients with CH-C (69.2 +/- 10.8%) was significantly lower than that for 5 normal controls (80.5 +/- 1.7%, P < 0.03). In 8 patients, the combination therapy of ribavirin (RBV) and interferon improved liver function but caused anemia. The filterability after treatment (57.8 +/- 12.8%) was lower than that before treatment (70.8 +/- 9.7%, P < 0.05). Decreased filterability showed no correlation with the mean corpuscular volume or mean corpuscular Hb concentration during treatment, suggesting that the decrease in filterability mainly arises from changes in erythrocyte membrane properties. We investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV-induced anemia. Filterability in 7 responders was markedly improved from 68.4 +/- 4.6% to 77.4 +/- 2.4% (P < 0.001), but not in 3 nonresponders. In the responders, the progression of anemia was restrained. In conclusion, we found an obvious impairment of the filterability of erythrocytes from CH-C patients, further impairment of the filterability induced by oxidative membrane damage caused by RBV leading to hemolytic anemia, and amelioration of the filterability caused by the antioxidative effects of EPA.

Adult↗
PubMed2007

Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2.

OBJECTIVES: Hepatitis C virus (HCV) infection is linked to greater insulin resistance. Although HCV itself is a candidate for the development of insulin resistance, the effects of antiviral treatment on impaired glucose metabolism remain unclear. The aim of this study is to examine the effects of clearance of HCV on insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate (IRS)1/2, central molecules for insulin signaling. METHODS: We analyzed 89 biopsy-proven patients with chronic HCV infection. Patients received interferon-alpha or interferon-alpha plus ribavirin for 6 months and were classified into three groups at 6 months after the conclusion of antiviral therapy according to their response to antiviral therapy: sustained responders (N = 29), relapsers (N = 12), and nonresponders (N = 48). Insulin resistance and beta-cell function were assessed by the homeostasis model assessment method (HOMA-IR and HOMA-%B, respectively). Hepatic expression of IRS1/2 was evaluated by immunoblotting and immunostaining in 14 sustained responders. RESULTS: In nonresponders and relapsers, there were no significant changes in HOMA-IR and HOMA-%B values after antiviral therapy. On the other hand, in sustained responders, HOMA-IR values significantly decreased to 1.7 +/- 0.8 from 3.1 +/- 1.1 (P < 0.05) after antiviral therapy. Similarly, HOMA-%B values significantly decreased to 90.6 +/- 10.0 from 113.7 +/- 15.3 (P < 0.05). Immunoblotting showed a threefold increase in IRS1/2 expression after clearance of HCV. Immunostaining revealed that greater IRS1/2 expression was seen in hepatocytes. CONCLUSIONS: We showed that clearance of HCV improves insulin resistance, beta-cell function, and hepatic IRS1/2 expression.

Biopsy↗
PubMed2007

Depletion of endothelial progenitor cells in the peripheral blood of patients with ulcerative colitis.

There is strong evidence to suggest that endothelial progenitor cells (EPCs) play a significant role in re-endothelialization and subsequent tissue repair. This study examined the role of EPCs in inflammatory bowel disease, a disease in which impairment of mucosal healing has been implicated. Peripheral blood mononuclear cells obtained from 50 patients with ulcerative colitis (UC), 29 patients with Crohn's disease (CD), 14 patients with infectious colitis, and 35 normal control subjects were cultured in EPC medium, harvested after 7 days, and characterized by immunocytochemistry and flow cytometry. Colony assay for hematopoietic progenitor cells was also performed. Patients with active UC had a significantly decreased number of circulating EPCs as compared with healthy controls (p=0.0013), patients with inactive UC (p=0.0099), patients with active CD (p=0.0235) and patients with infectious colitis (p=0.0002). On the other hand, patients with infectious colitis had a significantly increased number of circulating EPCs as compared with healthy controls (p=0.0406), patients with active UC (p=0.0002), and patients with active CD (p=0.0316). In patients with UC, the number of circulating EPCs was correlated with the serum hemoglobin levels (r=0.485, p=0.007) and inversely with the platelet count (r=-0.372, p=0.0382). The number of hematopoietic progenitor cell colonies was comparable among patients with UC, patients with CD, patients with infectious colitis, and healthy controls. Our observations indicate that the number of circulating EPCs in patients with UC is significantly reduced. Further studies are needed to define the mechanisms that underlie the reduction in the number of circulating EPCs and to better understand the pathophysiological consequences of this event in patients with UC.

Adult↗
PubMed2006

Cell cycle regulation by the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line.

BACKGROUND: Wee1 kinase plays a critical role in maintaining G2 arrest through its inhibitory phosphorylation of cdc2. In previous reports, a pyridopyrimidine molecule PD0166285 was identified to inhibit Wee1 activity at nanomolar concentrations. This G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 muM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. We herein report one of the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma cell line. METHODS: Tumor cell proliferation was determined by counting cell numbers. Cell cycle distribution was determined by flow cytometry. Morphogenesis analysis such as microtubule stabilization, Wee1 distribution, and cyclin B location were observed by immunofluorescence confocal microscopy. An immunoblot analysis of cdc2-Tyr15, cyclin D, E, p16, 21, 27, and Rb. A real-time PCR of the mRNA of cyclin D were completed. RESULTS: In our experiment, B16 cells also dramatically abrogated the G2 checkpoint and were found to arrest in the early G1 phase by treatment with 0.5 muM for 4 hours observed by flow cytometry. Cyclin D mRNA decreased within 4 hours observed by Real-time PCR. Rb was dephosphrylated for 24 hours. However, B16 cells did not undergo cell death after 0.5 muM treatment for 24 hours. Immnofluoscence microscopy showed that the cells become round and small in the morphogenesis. More interesting phenomena were that microtubule stabilization was blocked, and Wee1 distribution was restricted after treatment for 4 hours. CONCLUSION: We analyzed the effect of Wee1 inhibitor PD0166285 described first by Wang in the G2 transition in the B16 melanoma cell line. The inhibitor PD0166285 abrogated G2/M checkpoint inducing early cell division. Moreover, we found that the treatment of cells with the inhibitor is related to microtubule stabilization and decrease in cyclin D transcription. These effects together suggest that Wee1 inhibitor may thus be a potentially useful anti-cancer therapy.

Animals↗
PubMed2006

Promyelocytic crisis of chronic myelogenous leukaemia during imatinib mesylate treatment.

An untreated 66-year-old woman with chronic myelogenous leukaemia (CML) in the chronic phase was initially given imatinib mesylate, rapidly achieving a good cytogenetic response with treatment. However, acute promyelocytic leukaemia complicated by a disseminated intravascular coagulation occurred 9 months after beginning imatinib treatment. Promyelocytic crisis of CML was diagnosed by demonstration of both BCR/ABL and PML/RAR alpha chimeric genes in leukaemic cells by karyotypic and fluorescence in situ hybridization analysis. Clonal evolution with addition of the PML/RAR alpha translocation may have arisen in the early chronic phase of CML, with expansion of this clone during imatinib treatment. Promyelocytic crisis of CML is rare; furthermore, we know of no previous report of promyelocytic crisis occurring during treatment with imatinib.

Aged↗
PubMed2006

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Administration, Oral↗
PubMed2006

Interleukin-6 trans-signaling in inflammatory bowel disease.

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Recent investigations support the important role of an interleukin-6 (IL-6) signaling pathway in the development of IBD. However, the molecular mechanisms of this pathway in the intestine remain incompletely understood. The circulating and intestinal levels of IL-6 as well as soluble IL-6 receptor (sIL-6R) are increased in patients with IBD. It is remarkable that the mucosal T cells of IBD patients are extremely resistant to apoptosis and that a large fraction of these cells express membrane-bound gp130 but not IL-6R. The accumulated evidence strongly supports the hypothesis that the development and perpetuation of IBD relies on the increased formation of IL-6/sIL-6R complexes interacting with membrane-bound gp130 on T cells via trans-signaling. These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling.

Animals↗
PubMed2006

High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma.

Insulin-like growth factor binding protein-3 (IGFBP-3) modulates cell proliferation of various cancer cell types. However, it remains unclear how IGF-IGFBP-3-signaling is involved in growth and progression of hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP-3 in HCC. Type 1 receptor for IGF (IGF-1R) was expressed at various levels in the seven lines examined, but IGF-2R was not expressed. Of the seven lines, the growth of HAK-1B, KIM-1, KYN-2 and HepG2 cells was stimulated in a dose-dependent manner by the exogenous addition of IGF-I or IGF-II, but the HAK-1A, KYN-1 and KYN-3 cell lines showed no growth. Exogenous addition of IGFBP-3 markedly blocked IGF-I and IGF-II-stimulated cell growth of KYN-2 and HepG2 cells, and moderately stimulated that of KIM-1 and HAK-1B cells, but no growth of the KYN-1, KYN-3 and HAK-1A cell lines was observed. IGF-I enhanced the phosphorylation of IGF-1R, Akt and Erk1/2 in KYN-2 cells, and coadministration of IGFBP-3 blocked all types of activation by IGF-I investigated here. In contrast, no such activation by IGF-I was detected in KYN-3 cells. IGFBP-3 also suppressed IGF-I-induced cell invasion by KYN-2 cells. Moreover, we were able to observe the apparent expression of IGFBP-3 in KYN-3 cells, but not in the other six cell lines. Furthermore reduced expression of IGFBP-3, but not that of IGF-1R, was significantly correlated with tumor size, histological differentiation, capsular invasion and portal venous invasion. Low expression of IGFBP-3 was independently associated with poor survival. IGFBP-3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC.

Aged↗
PubMed2006

Identification of hepatitis C virus (HCV) 2a-derived epitope peptides having the capacity to induce cytotoxic T lymphocytes in human leukocyte antigen-A24+ and HCV2a-infected patients.

Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in preventing the spread of hepatitis C virus (HCV), vaccine-based HCV-specific CTL induction could be a promising strategy to treat HCV-infected patients. In this study, we tried to identify HCV2a-derived epitopes, which can induce human leukocyte antigen (HLA)-A24-restricted and peptide-specific CTLs. Peripheral blood mononuclear cells of HCV2a-infected patients or healthy donors were stimulated in vitro with HCV2a-derived peptides, which were prepared based on the HLA-A24 binding motif. As a result, three peptides (HCV2a 576-584, HCV2a 627-635, and HCV2a 1085-1094) efficiently induced peptide-specific CTLs from HLA-A24(+) HCV2a-infected patients as well as healthy donors. The cytotoxicity was exhibited by peptide-specific CD8(+) T cells in an HLA-A24-restricted manner. In addition, the HCV2a 627-635 peptide was frequently recognized by immunoglobulin G of HCV2a-infected patients. These results indicate that the identified three HCV2a peptides might be applicable to peptide-based immunotherapy for HLA-A24(+) HCV2a-infected patients.

Cell Line, Tumor↗
PubMed2006

Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan.

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p<0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p<0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.

Journal Article↗
PubMed2006

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.

Journal Article↗
PubMed2006

Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation.

There is a growing body of evidence to show that that C-reactive protein (CRP), an acute phase reactant, is one of the most valuable predictors of future cardiovascular events. Since CRP proteins directly contribute to the development and progression of atherosclerosis as well, reduction of CRP levels may be a novel therapeutic target for the treatment of cardiovascular disease. In this study, we examined whether pigment epithelium-derived factor (PEDF) could block the interleukin-6-induced CRP expression in cultured human hepatoma cells and the way that it might achieve this effect. PEDF inhibited the IL-6-induced CRP expression in Hep3B cells at both mRNA and proteins levels. PEDF suppressed the intracellular reactive oxygen species generation in IL-6-exposed Hep3B cells. Anti-oxidants mimicked the effects of PEDF. PEDF was also found to inhibit the IL-6-elicited Rac-1 activation, whereas dominant-negative Rac-1 dose-dependently decreased the CRP mRNA levels. PEDF blocked the IL-6-induced STAT3 phosphorylations and NF-kappaB p65 activity in Hep3B cells. Our present study suggests that PEDF could be one of the potent suppressors of CRP production by the liver and may play a protective role against atherosclerosis.

Antibodies, Monoclonal↗
PubMed2006

Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: an implication for the antitumor potential of flavonoids.

In this study, we have investigated the underlying molecular mechanism for the potent proapoptotic effect of luteolin on human hepatoma cells both in vitro and in vivo, focusing on the signal transducer and activator of transcription 3 (STAT3)/Fas signaling. A clear apoptosis was found in the luteolin-treated HLF hepatoma cells in a time- and dosage-dependent manner. In concert with the caspase-8 activation by luteolin, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr(705) phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was found within 20 minutes in the luteolin-treated cells, leading to down-regulation in the target gene products of STAT3, such as cyclin D1, survivin, Bcl-xL, and vascular endothelial growth factor. Of interest, the rapid down-regulation in STAT3 was consistent with an accelerated ubiquitin-dependent degradation in the Tyr(705)-phosphorylated STAT3, but not the Ser(727)-phosphorylated one, another regulator of STAT3 activity. The expression level of Ser(727)-phosphorylated STAT3 was gradually decreased by the luteolin treatment, followed by a fast and clear down-regulation in the active forms of CDK5, which can phosphorylate STAT3 at Ser(727). An overexpression in STAT3 led to resistance to luteolin, suggesting that STAT3 was a critical target of luteolin. In nude mice with xenografted tumors using HAK-1B hepatoma cells, luteolin significantly inhibited the growth of the tumors in a dosage-dependent manner. These data suggested that luteolin targeted STAT3 through dual pathways-the ubiquitin-dependent degradation in Tyr(705)-phosphorylated STAT3 and the gradual down-regulation in Ser(727)-phosphorylated STAT3 through inactivation of CDK5, thereby triggering apoptosis via up-regulation in Fas/CD95.

Animals↗
PubMed2006

Pigment epithelium-derived factor (PEDF) inhibits advanced glycation end product (AGE)-induced C-reactive protein expression in hepatoma cells by suppressing Rac-1 activation.

Serum levels of advanced glycation end products (AGEs) are associated with an acute phase reactant, C-reactive proteins (CRP) in diabetic patients. However, whether AGEs could directly stimulate hepatic CRP production remains to be elucidated. We found here that AGEs upregulated CRP mRNA levels in cultured Hep3B cells via Rac-1 activation, which was blocked by pigment epithelium-derived factor (PEDF). Our present study suggests that AGEs are one of the potent inducers of CRP and that PEDF may work as an anti-inflammatory agent against AGEs in the liver.

C-Reactive Protein↗
PubMed2006

A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C.

BACKGROUND/AIMS: In eastern Asian countries, hepatitis B virus (HBV) genotype Ba (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response or resistance to lamivudine therapy among patients with different HBV genotypes. METHODS: Of 67 Japanese and Chinese patients with chronic hepatitis B, 18 patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case-control study matched according to gender and age. All the patients were treated with lamivudine for 2 years and evaluated the response or emergence of the YMDD mutation at year 2 during the treatment. HBV genotypes were detected by the restriction fragment length polymorphism. The YMDD mutation was detected by the direct sequencing after amplification by PCR. RESULTS: At year 2 during therapy, 44.8% of the patients showed normalization of ALT and undetectable HBV DNA (favorable response), 35.8% developed the YMDD mutation. There was no significant difference of response to the therapy among the three genotype groups. The emergence of the YMDD mutation was associated with HBV/C. By the multiple logistic regression analysis, however, the significant factor of a favorable response was a higher pretreatment ALT level and negative HBeAg status and the significant factor of the emergence of the YMDD mutation was HBV/C. CONCLUSIONS: Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the response or resistance to lamivudine therapy.

Journal Article↗
PubMed2006

Angiogenic cell therapy for hepatic fibrosis.

Progression of liver fibrosis has been linked with injuries associated with hypoxia and neovascularization. Neovascularization consists of angiogenesis and vasculogenesis, representing formation of blood vessels by differentiation of endothelial progenitor cells (EPCs). We investigated antifibrogenic and regenerative effects of EPC transplantation in chronic liver injury. Rat EPCs were isolated from bone marrow cells and examined in vitro for lineage markers. Recipient rats were injected intraperitoneally with dimethylnitrosamine (DMN) three times weekly for 4 weeks, plus EPC transplantation once weekly for 4 weeks. Transplanted rats showed suppression of liver fibrogenesis. Expression of growth factors promoting liver regeneration such as hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) was increased in transplanted rats, together with hepatocyte proliferation. Normal liver function parameters such as transaminase, total bilirubin, total protein, and albumin were maintained in transplanted rats. EPC transplantation is effective not only for preventing liver fibrosis but also for promoting regeneration in chronically damaged livers. Also, recently it has been reported that green fluorescent protein-positive bone marrow cells contribute to the liver tissue repair of fibrosis model rats. EPC transplantation might become an alternative if further preclinical investigation finds it to be effective in severely cirrhotic livers.

Animals↗
PubMed2006

Liposome-mediated gene transfer of K1-5 suppresses tumor development and improves the prognosis of hepatocellular carcinoma in mice.

It has been reported that kringle 1-5 (K1-5) has a potent and specific antiangiogenic activity. In the present study, we investigated the antitumor effect of gene transfer of K1-5 for hepatocellular carcinoma in mice. Inhibitory effect by the media of Cos-1 cells containing K1-5 on bovine capillary endothelial (BCE) cell proliferation was evaluated by a tetrazolium-based assay. For tumor growth, intrahepatic metastasis, and survival studies, intravenous injection of liposome-K1-5 cDNA complexes was performed to nude mice implanted with three hepatoma cell lines into the liver. Production of K1-5 was investigated by immunohistochemistry and Western blotting. The number of vessels in the tumor was counted in 0.125 mm2 fields. Expression of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and -2 in tumors was investigated by Western blotting. Serum ALT levels and body weight of the mice were measured. Proliferation of BCE cells was inhibited by 44% in the media containing K1-5. Gene transfer of K1-5 suppressed tumor growth of the three hepatoma cell lines, respectively. In the K1-5-treated group, survival period was prolonged and the number of intrahepatic metastases was reduced. Expression of K1-5 protein was detected on hepatoma cells and hepatocytes. The number of vessels in tumor tissues was decreased by K1-5 transfection. Expression of angiopoietin-2 in tumor tissues was suppressed by K1-5 transfection. Serum ALT levels and body weight of mice were not influenced by K1-5 transfection. These findings suggest that antiangiogenic gene therapy with K1-5 cDNA will be a safe and effective strategy to suppress the growth of hepatocellular carcinoma.

Alanine Transaminase↗