Kotaro Kawaguchi

Iwakuni Clinical Center, Ивакуни, Yamaguchi, Japan

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Publications (6)21.34 Total impact

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    ABSTRACT: Background/Aim: In liver fibrosis, activated hepatic stellate cells (HSC) are transformed into myofibroblasts. Helix-loop-helix (HLH) transcriptional factors such as MyoD regulate the differentiation of myocytes, and the inhibitor of DNA binding/differentiation (Id) family comprises dominant negative HLH transcriptional regulators that inhibit differentiation and promote cell proliferation. In the present study, we investigated how the Id family proteins regulate HSC. Methods: In primary rat HSC, inhibitor of DNA binding/differentiation (Id)2 and α-smooth muscle actin (α-SMA) mRNA expression increased 4 days after isolation. Next we established Id2 expressing HSC (HSC-T6-Id2-green fluorescent protein (GFP)) using HSC-T6 cells with retrovirus that expressed GFP-tagged Id2. Results: HSC-T6-Id2-GFP increased cell proliferation with cyclin D1 expression. In contrast, α-SMA expression wassuppressed. Real-time reverse transcription–polymerase chain reaction analysis showed Id2 induction significantly suppressed α-SMA, collagen-1, matrix metalloproteinase (MMP)-2, and MMP-9 mRNA (P < 0.05) but had no effect on tissue inhibitor of metalloproteinase or transforming growth factor-β1 levels. Conclusion: These findings suggest Id2, an HLH transcriptional regulator, plays an important regulatory role in the proliferation and differentiation of HSC.
    No preview · Article · Aug 2007 · Hepatology Research
  • Isao Sakaida · Kotaro Kawaguchi · Teruaki Kimura · Fusako Tamura · Kiwamu Okita
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    ABSTRACT: We report a 13-year-old girl who presented with hepatic failure and hemolytic anemia. Laboratory findings showed a normal serum copper level (104 microg/dl), high urinary copper level (2370 microg/dl), and low serum ceruloplasmin level (14.3 microg/dl). Slit-lamp examination revealed Kayser-Fleischer rings on her cornea, and she was diagnosed with Wilson's disease. Plasma exchange and continuous hemodiafiltration relieved the serious condition, after that laparoscopic examination was performed. Administration of D-penicillamine and restriction of dietary copper (<1 mg/day) were started, leading to a normalized serum alanine amino transferase (ALT) level. After 3 years, she again underwent laparoscopic examination, and the laparoscopic and histological findings of her liver were obviously improved. Management of the copper level can reverse severe liver fibrosis in Wilson's disease.
    No preview · Article · Jul 2005 · Journal of Gastroenterology
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    ABSTRACT: We have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode. We studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment. One session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12 min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 +/- 7.8 mm; greatest short-axis dimension, 33.4 +/- 7.5 mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 +/- 4.7 mm; greatest short-axis dimension, 25.9 +/- 3.7 mm; P = 0.002 for greatest long-axis dimension; P = 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA. We consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.
    No preview · Article · Mar 2005 · Journal of Gastroenterology
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    ABSTRACT: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC). Forty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics. Of all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables--the Child-Pugh score (P = 0.013, P = 0.018), alpha-fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors. Patients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.
    No preview · Article · Feb 2005 · Journal of Gastroenterology
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    ABSTRACT: Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis have a risk of development of hepatocellular carcinoma. Peroxisome proliferator-activated receptor (PPAR) gamma ligand has recently been reported to have improved the condition of patients with NASH. The aim of this study was to investigate whether pioglitazone, a PPARgamma ligand, has any influence on the animal model of NASH as well as isolated hepatic stellate cells. In vivo, the effects of pioglitazone were examined using the choline-deficient L-amino acid-defined (CDAA)-diet liver fibrosis model. After two weeks, pioglitazone improved hepatic steatosis, prevented liver fibrosis, and reduced preneoplastic lesions in the liver after 10 weeks. Pioglitazone reduced the expression of TIMP-1 and TIMP-2 mRNA without changing MMP-13 mRNA expression compared to the liver fed a CDAA diet alone. In vitro, pioglitazone prevented the activation of hepatic stellate cells resulting in reducing the expression of type I procollagen, MMP-2, TIMP-1, and TIMP-2 mRNA with increased MMP-13 mRNA expression. These results indicate that pioglitazone may be one of the candidates for the benefit drugs for the liver disease of patients with NASH.
    No preview · Article · Mar 2004 · Biochemical and Biophysical Research Communications
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    ABSTRACT: The authors report the efficacy of arterial infusion chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), and leucovorin (LV) for patients with advanced hepatocellular carcinoma (HCC). In this study, we evaluated the efficacy of our regimen with high-dose LV, using isovorin (IV) (high dose group), comparing the previous regimen (low-dose LV; low dose group). This is a retrospective, historical, and non-controlled trial. In the high dose group (n=15), one course of chemotherapy consisted of the daily administration of CDDP (10 mg/1 h, for 5 days) and IV (12.5 mg/10 min, for 5 days) followed by 5-FU (250 mg/5 h, for 5 days). In the low dose group (n=9), changing to the administration of LV (12 mg/day), the same regimen was employed. In principle, we did this 20 times. In the high dose group, complete response (CR) was found in two patients, and partial response (PR) in six patients. Thus, the response rate was 53%. In the low dose group, CR was found in two patients, and PR in three patients. Thus, the response rate was 56%. There were no significant differences in the response rate (P=0.71), the survival rate (P=0.29) and the toxicity between the two groups. We considered the recommended dose of LV to be 12 mg/day in our regimen, although this is a preliminary study.
    No preview · Article · Oct 2003 · Hepatology Research

Publication Stats

200 Citations
21.34 Total Impact Points


  • 2007
    • Iwakuni Clinical Center
      Ивакуни, Yamaguchi, Japan
  • 2004-2005
    • Yamaguchi University
      • Department of Gastroenterology and Hepatology
      Yamaguti, Yamaguchi, Japan