Bazarragchaa Damdinsuren

Publications (36)122.18 Total impact

• Article: [A case of HCC with inferior caval vein tumor thrombus and multiple pulmonary metastases that remarkably responded to combination therapy of TS-1 and interferon-alpha].

  Masato Nakamura, Hiroaki Nagano, Masato Sakon, Tameyoshi Yamamoto, Hideo Ota, Hiroshi Wada, Shinichi Yoshioka, Hitoshi Kato, Bazarragchaa Damdinsuren, Shigeru Marubashi, Atsushi Miyamoto, Yutaka Takeda, Koji Umeshita, Shoji Nakamori, Keizo Dono, Morito Monden
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  ABSTRACT: A 56-year-old male was admitted to our hospital for hepatoma with portal vein thrombus and multiple intrahepatic metastases. He underwent an extended left lobectomy and a partial resection of the liver in May 2002. After two weeks from the surgery, he received intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat the lesions in the residual liver. Four months after the surgery, hepatic vein tumor thrombus appeared in the remnant liver and it extended to the inferior caval vein. And another 4 months later, multiple pulmonary metastases were detected with computed tomography and they grew rapidly in the view of their sizes and numbers. Because the combined therapy of 5-FU/interferon-alpha was not effective to distant metastases, we started a new regimen of oral administration of TS-1 and a subcutaneous interferon-alpha injection. After 1 treatment cool, hepatic vein thrombus was markedly reduced the size and vascularity in the CT. Multiple pulmonary metastases also decreased in their sizes and numbers. No adverse effect was seen during this treatment. It was suggested that a combination therapy of TS-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastasis.
  Gan to kagaku ryoho. Cancer & chemotherapy 11/2005; 32(11):1824-8.
• Article: [A successful surgical treatment for solitary pulmonary and adrenal metastases after hepatic resection to hepatocellular carcinoma--a case report].

  Hiroshi Wada, Hiroaki Nagano, Masato Nakamura, Shinichi Yoshioka, Hitoshi Kato, Takehiro Noda, Bazarragchaa Damdinsuren, Shigeru Marubashi, Atsushi Miyamoto, Yutaka Takeda, Koji Umeshita, Keizo Dono, Morito Monden
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  ABSTRACT: We report a 65-year-old man who received a successful surgical treatment for both pulmonary and adrenal metastases after curative resection to hepatocellular carcinoma (HCC). He received a partial hepatic resection for HCC of the right hepatic lobe. Thirty-eight months after the first hepatic resection, a metastatic lesion of the right pulmonary lobe was detected by computed tomography (CT). He was orally administered of UFT (600 mg/day). After 6 months of the chemotherapy, a metastatic lesion of lung became decreased in size. However, a metastatic lesion of the right adrenal gland was detected by abdominal CT scan. Fifty six months after the first operation, we performed right adrenalectomy. A further 4 months later, we performed partial resection of the right pulmonary lobe. Eight months after the pulmonary resection, intrahepatic recurrence was detected and he received transcatheter arterial embolization (TAE) twice. Eighty one months after the first operation, he died of liver failure due to tumor progression. Surgical resection for metastases from HCC resulted in long-term survival even if there were extrahepatic metastases in two different sites.
  Gan to kagaku ryoho. Cancer & chemotherapy 11/2005; 32(11):1835-8.
• Article: Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells.

  Hikaru Izawa, Hirofumi Yamamoto, Bazarragchaa Damdinsuren, Kimimasa Ikeda, Masaki Tsujie, Rei Suzuki, Kotaro Kitani, Yosuke Seki, Taro Hayashi, Ichiro Takemasa, Masataka Ikeda, Masayuki Ohue, Mitsugu Sekimoto, Takushi Monden, Morito Monden
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  ABSTRACT: The cyclin-dependent kinase inhibitor p21cip1/waf1 negatively regulates the progression of cell cycle and the potential usefulness of p21cip1/waf1 gene is proposed in gene therapy. However, studies have demonstrated a protective role of p21cip1/waf1 against apoptosis and little is known about effects of ectopic expression of p21cip1/waf1 on differentiation of colon cancer cells. In the present study, we found diffuse p21cip1/waf1 expression in only a few clinical samples of colorectal cancer with wild-type p53 gene. To explore the role of p21cip1/waf1 in cell growth, apoptosis and differentiation, we constitutively overexpressed p21cip1/waf1 in HT29 colon carcinoma cells. Ectopic overexpression of p21cip1/waf1 was associated with inhibition of CDK2-associated kinase activity, indicating the functionality of the introduced p21cip1/waf1 gene. Overexpression of p21cip1/waf1 caused an appreciable growth inhibition in monolayer and soft agar cultures and it significantly reduced sodium butyrate- but not 5-fluorouracil-induced apoptosis. p21cip1/waf1 overexpressing cells exhibited marked decrease of intestinal differentiation when assayed with intestinal alkaline phosphatase. Our findings suggest that introduction of p21cip1/waf1 gene into colon cancer cells may be useful for inhibiting cell growth but caution should be taken regarding the increased resistance to certain apoptosis-inducing agents and dysregulation of endogenous p21cip1/waf1-mediated differentiation process.
  International Journal of Oncology 08/2005; 27(1):69-76. · 2.40 Impact Factor
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  Available from: dkfz.de

  Article: Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues.

  Byung No Kim, Hirofumi Yamamoto, Kimimasa Ikeda, Bazarragchaa Damdinsuren, Yurika Sugita, Chew Yee Ngan, Yujiro Fujie, Minoru Ogawa, Taishi Hata, Masataka Ikeda, Masayuki Ohue, Mitsugu Sekimoto, Takushi Monden, Nariaki Matsuura, Morito Monden
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  ABSTRACT: It is known that p16(INK4) tumor suppressor gene expression in colon cancer cells is repressed by methylation at the CpG island of promoter, but in vivo silencing of p16 gene is not fully understood. Some studies showed that primary colorectal cancer (CRC) tissues often overexpress the p16 protein, while others showed the high incidence of p16 methylation. The aim of this study was to clarify p16 gene regulation in vivo. We used real-time methylation-specific PCR (MSP) to examine density of p16 methylation, and immunohistochemistry, Western blot analysis to determine p16 protein expression. Methylation was detected in 5 CRC cell lines tested and 9 of 21 (42.9%) CRCs. Four of 5 CRC cell lines did not express p16 mRNA, but 6 of 9 CRCs did express p16 mRNA even with methylation. Real-time MSP showed that CRC tissues had a wide variety in methylation density (methylation index: 0.28-0.91) and that highly methylated CRC tissues displayed significantly lower p16 mRNA expression than those with no-methylation or low-methylation. Immunohistochemistry showed that the majority of CRCs (53 of 55: 96.4%) overexpressed the p16 protein. Low p16 expression was associated with lymph node metastasis (p=0.003) and large tumor size (p=0.048). Western blot in a subset of non-tumor and tumor samples showed a consistent overexpression of the p16 protein. These results showed that CRC tissues displayed variable methylation density, which may be characteristics of p16 gene methylation in vivo. Our data suggest that a low p16 expression due to methylation may contribute to tumor enlargement and expansion of CRC.
  International Journal of Oncology 06/2005; 26(5):1217-26. · 2.40 Impact Factor
• Article: Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.

  Bazarragchaa Damdinsuren, Hiroaki Nagano, Motoi Kondo, Hirofumi Yamamoto, Nobuaki Hiraoka, Tameyoshi Yamamoto, Shigeru Marubashi, Atsushi Miyamoto, Koji Umeshita, Keizo Dono, Shoji Nakamori, Ken-Ichi Wakasa, Masato Sakon, Morito Monden
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  ABSTRACT: Several studies reported that Id (Inhibitor of DNA binding or Differentiation) proteins, helix-loop-helix transcription factors, have important roles in differentiation, cell cycle and angiogenesis in various cells. However, the role of Id proteins in hepatocellular carcinoma (HCC) remains unclear. We examined the immunohistochemical expression of Id1, Id2 and Id3 proteins in 54 surgically resected HCCs with surrounding HCV or HBV-related chronic hepatitis (n=30) and liver cirrhosis (n=24). All non-cancerous livers exhibited immunoreactivity for Id proteins and the expression increased from chronic hepatitis to cirrhosis. In HCCs (n=45), well-differentiated tumors mostly exhibited strong or moderate immunostaining for all Id proteins, while proportion of the samples with weak or no expression increased with tumor dedifferentiation and frequently observed in poorly (66.7, 93.3 and 93.3% respectively for Id1, 2, 3) or undifferentiated (100% for all Ids) HCCs. Clinicopathological survey demonstrated a significant correlation between Id1, 2 and 3 expression and differentiation of carcinoma (p=0.0044, 0.0014 and 0.0014, respectively) although univariate analysis indicated that high expression of Id1 was significant predictive factor for longer disease-free survival of the patients (p=0.047). A similar tendency was also observed with Id2 and Id3. The present study demonstrate high expression of Id1, 2 and 3 in well-differentiated HCC and low expression in advanced dedifferentiated HCC, in contrast to its continuous expression during breast, prostate and colon carcinogenesis. These findings suggested that Id1, 2 and 3 might play a role in the early stages of hepatocarcinogenesis, but not in the development of advanced carcinoma, and might consequently be related to HCC dedifferentiation.
  International Journal of Oncology 03/2005; 26(2):319-27. · 2.40 Impact Factor
• Article: Association between recurrence of hepatocellular carcinoma and alpha-fetoprotein messenger RNA levels in peripheral blood.

  Osakuni Morimoto, Hiroaki Nagano, Atsushi Miyamoto, Yoshiyuki Fujiwara, Motoi Kondo, Tameyoshi Yamamoto, Hideo Ota, Masato Nakamura, Hiroshi Wada, Bazarragchaa Damdinsuren, Shigeru Marubashi, Keizo Dono, Koji Umeshita, Shoji Nakamori, Masato Sakon, Morito Monden
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  ABSTRACT: Intra- and extrahepatic recurrence is common, even after curative resection for hepatocellular carcinoma (HCC), suggesting preoperative or intraoperative tumor cell dissemination. Reverse transcription - polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) is used to detect circulating liver cancer cells. We previously developed a quantitative method that allows estimation of the AFP mRNA level by real-time PCR. In the present study, we used this method to measure the AFP mRNA level before and after resection of HCC, then correlated the findings with various clinicopathological characteristics and prognosis. We prospectively examined peripheral blood samples from 38 patients with HCC, and bone marrow aspirate from 25 of these patients. As a control, we examined bone marrow from 20 patients with benign diseases. The follow-up period ranged from 32 to 66 months. Real-time RT-PCR was used to detect AFP mRNA levels in the samples. AFP was expressed in 9 (23.7%) of the 38 peripheral blood samples. The detection of AFP mRNA was significantly correlated with extrahepatic metastasis after primary surgery, and a shorter disease-free survival time (P = 0.0245 each). Bone marrow samples were defined as positive if they expressed AFP mRNA at levels higher than the maximum expressed level in the controls, because only 1 (5%) of the 20 control bone marrow samples had low AFP mRNA expression. Using this cutoff level, 12 (48%) of the 25 patients with HCC had positivity for AFP mRNA. The results of bone marrow RT-PCR did not correlate with the clinocopathological characteristics of prognosis. Using real-time PCR to measure the AFP mRNA level in blood, but not bone marrow, could be useful for predicting postoperative tumor recurrence.
  Surgery Today 02/2005; 35(12):1033-41. · 1.22 Impact Factor
• Article: Combination of IFN-alpha and 5-fluorouracil induces apoptosis through IFN-alpha/beta receptor in human hepatocellular carcinoma cells.

  Motoi Kondo, Hiroaki Nagano, Hiroshi Wada, Bazarragchaa Damdinsuren, Hirofumi Yamamoto, Nobuaki Hiraoka, Hidetoshi Eguchi, Atsushi Miyamoto, Tameyoshi Yamamoto, Hideo Ota, Masato Nakamura, Shigeru Marubashi, Keizo Dono, Koji Umeshita, Shoji Nakamori, Masato Sakon, Morito Monden
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  ABSTRACT: Several studies showed the effectiveness of combination therapy with IFN-alpha and 5-fluorouracil (5-FU) for advanced hepatocellular carcinoma. However, only little is known about the underlying mechanism of combination therapy. In the present study, we examined whether apoptosis through IFN-alpha/beta receptor (IFN-alpha/betaR) was associated with the effects of combination therapy. HuH7, PLC/PRF/5, HLE, and HLF were treated with IFN- (500 units/mL), 5-FU (0.5 microg/mL), or their combination for 10 days. In addition, IFN-alpha/betaR gene transfer with combination therapy was done. Ten-day treatment by combination therapy resulted in >80% cell growth inhibition. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis showed synergistic effects for combination therapy on PLC/PRF/5, HLE, and HLF. Concordant results were obtained with DNA fragmentation. Moreover, there was an evidence showing that changes in the expression of Bcl-2 family lead to apoptosis. On the other hand, the expression of IFN-alpha/betaR and up-regulation of alpha-phospho-signal transducer and activator of transcription 1, IFN regulatory factor-1 by combination therapy were observed in all cell lines. Furthermore, IFN-alpha/type 2 IFN receptor long form-transfected HuH7 cells treated with combination therapy showed strong DNA fragmentation compared with nontransfected or transfected with IFN-alpha- and 5-FU-treated HuH7. Our results showed that combination of IFN-alpha plus 5-FU strongly induced cell growth inhibition of human hepatocellular carcinoma cells and indicated that one of the direct mechanisms of combination therapy may in part be attributable to alterations in induction of apoptosis through IFN-alpha/betaR.
  Clinical Cancer Research 02/2005; 11(3):1277-86. · 7.74 Impact Factor
• Article: Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.

  Tameyoshi Yamamoto, Hiroaki Nagano, Masato Sakon, Hisashi Wada, Hidetoshi Eguchi, Motoi Kondo, Bazarragchaa Damdinsuren, Hideo Ota, Masato Nakamura, Hiroshi Wada, Shigeru Marubashi, Atsushi Miyamoto, Keizo Dono, Koji Umeshita, Shoji Nakamori, Hideo Yagita, Morito Monden
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  ABSTRACT: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.
  Clinical Cancer Research 01/2005; 10(23):7884-95. · 7.74 Impact Factor
• Article: [Successful treatment for advanced cholangiocellular carcinoma with intrahepatic metastasis and/or portal vein tumor thrombi by intraarterial chemotherapy combined with 5-fluorouracil, adriamycin and cisplatin (FAP)--two cases report].

  Hiroshi Wada, Hiroaki Nagano, Keizo Dono, Motoi Kondo, Tameyoshi Yamamoto, Hideo Ota, Masato Nakamura, Shinichi Yoshioka, Bazarragchaa Damdinsuren, Yang Yubo, Shigeru Marubashi, Atsushi Miyamoto, Koji Umeshita, Shoji Nakamori, Masato Sakon, Morito Monden
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  ABSTRACT: The patients of unresectable cholangiocellular carcinoma (CCC) have extremely poor prognosis. Case 1 was a 72-year-old male who had CCC in the left lobe of liver with intrahepatic metastasis. From June 2003, he received hepatic arterial infusion chemotherapy (FAP: 5-fluorouracil 250 mg/day continuous infusion, day 1-5, adriamycin 10 mg/day, day 1, and CDDP 10 mg/day, day 1). After 5 courses, abdominal CT revealed that the main tumor had regressed. Case 2 was a 66-year-old male who had CCC with portal vein tumor thrombus of anterior branch (Vp2). He received FAP arterial infusion chemotherapy that was a same regimen as with the case 1 patient. After 5 courses were administered, Abdominal CT revealed that the size of the main tumor at S8 had not changed, and that portal vein tumor thrombus had disappeared. In both cases, there was no complication related to the chemotherapy. They are alive for more than 1 year after chemotherapy had started. FAP hepatic arterial infusion chemotherapy might be promising as an effective therapy for non-resectable CCC without extra hepatic metastasis.
  Gan to kagaku ryoho. Cancer & chemotherapy 11/2004; 31(11):1711-3.
• Article: [A case of long-term survivor with multiple pulmonary metastases of HCC after hepatic resection].

  Masato Nakamura, Hiroaki Nagano, Masato Sakon, Motoi Kondo, Tameyoshi Yamamoto, Hideo Ota, Hiroshi Wada, Bazarragchaa Damdinsuren, Yubo Yang, Shigeru Marubashi, Atsushi Miyamoto, Keizo Dono, Koji Umeshita, Shoji Nakamori, Morito Monden
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  ABSTRACT: A 52-year-old male was admitted to our hospital with huge hepatoma of the right lobe. He underwent a right lobectomy of the liver in July 1999. After five months from the surgery, multiple recurrences in the liver and lung were revealed with Computed tomography (CT). TAE was performed for intrahepatic recurrence and a combination therapy, consisting of UFT and interferon-alpha, was started for pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001 and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the patient survived for 31 months with no disturbance in quality of life. No intrahepatic recurrence was also detected during the survival period. It was suggested that a good prognosis may be expected, even in the HCC case with distant metastasis after hepatic resection, if the primary cite was curatively treated.
  Gan to kagaku ryoho. Cancer & chemotherapy 11/2004; 31(11):1939-42.
• Article: Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

  Minoru Ogawa, Hirofumi Yamamoto, Hiroaki Nagano, Yasuhiro Miyake, Yurika Sugita, Taishi Hata, Byung-No Kim, Chew Yee Ngan, Bazarragchaa Damdinsuren, Masakazu Ikenaga, Masataka Ikeda, Masayuki Ohue, Shoji Nakamori, Mitsugu Sekimoto, Masato Sakon, Nariaki Matsuura, Morito Monden
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  ABSTRACT: We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.
  Hepatology 03/2004; 39(2):528-39. · 11.66 Impact Factor
• Article: Interferon-beta is more potent than interferon-alpha in inhibition of human hepatocellular carcinoma cell growth when used alone and in combination with anticancer drugs.

  Bazarragchaa Damdinsuren, Hiroaki Nagano, Masato Sakon, Motoi Kondo, Tameyoshi Yamamoto, Koji Umeshita, Keizo Dono, Shoji Nakamori, Morito Monden
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  ABSTRACT: The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor, but promising effects of chemotherapies combined with interferon (IFN) have been reported. To develop more effective combination therapies for HCC, we compared the antiproliferative effects of IFN-alpha and IFN-beta in combination with various cytotoxic drugs on hepatoma cell lines using MTT assay and isobologram analysis. IFN-beta was more potent than IFN-alpha in inhibiting the cell growth of all cell lines (P <.05, two-way ANOVA). PLC/PRF/5 was more sensitive to either IFN, than HLE and HuH7. Cell growth of all cell lines was inhibited in a dose-dependent manner by 5-fluorouracil (5-FU), cisplatin (CDDP), and doxorubicin (DOX), but the sensitivities of these cells were considerably different. As for IFN-alpha, synergistic effects were observed when combined with 5-FU and DOX on PLC/PRF/5 cells only, whereas IFN-beta showed synergistic effects with 5-FU and CDDP on HuH7 and PLC/PRF/5 cell lines. The spectra of the antiproliferative activity and synergistic effect of IFN-beta when combined with anticancer drugs are more potent than those of IFN-alpha. Combinations of IFN-beta and anticancer drugs may provide a better treatment of HCC when combinations with IFN-alpha are ineffective.
  Annals of Surgical Oncology 12/2003; 10(10):1184-90. · 4.17 Impact Factor
• Article: JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1.

  Hirofumi Yamamoto, Motoi Kondo, Shoji Nakamori, Hiroaki Nagano, Ken-Ichi Wakasa, Yurika Sugita, Jin Chang-De, Shogo Kobayashi, Bazarragchaa Damdinsuren, Keizo Dono, Koji Umeshita, Mitsugu Sekimoto, Masato Sakon, Nariaki Matsuura, Morito Monden
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  ABSTRACT: The aim of this study was to assess the effects of cyclooxygenase (COX)-2 inhibition on rat experimental liver fibrogenesis. We investigated the inhibitory effects of a selective COX-2 inhibitor, JTE-522, on liver fibrosis induced by a choline-deficient, l-amino acid-defined diet (CDAA). Inhibitory effect was also tested in a second model of thioacetamide (TAA)-induced liver fibrosis. CDAA induced liver fibrosis and preneoplastic foci at 12 weeks and cirrhosis at 36 weeks. Hepatocellular carcinoma was noted in 13 of 15 rats (87%). JTE-522 significantly inhibited fibrosis and development of preneoplastic lesions in a dose-dependent manner and completely inhibited generation of cirrhosis and hepatocellular carcinoma at both low and high doses (10 and 30 mg/kg body wt/day, respectively). JTE-522 administrated only from 12 weeks to 36 weeks also prevented cirrhosis and formation of hepatocellular carcinoma. JTE-522 itself did not cause local or systemic gross or histopathologic changes at 36 weeks. Mechanistic studies indicated that the CDAA model displayed up-regulation of several biomarkers, including COX-2, arachidonate metabolite (prostaglandin E(2)), serum aspartate aminotransferase, and c-myc expression. The model also showed an increased proportion of activated hepatic stellate cells, proliferating cell nuclear antigen index, and CD45-positive inflammatory cells in the liver. JTE-522 effectively diminished these changes. JTE-522 exhibited similar antifibrosis effects in the TAA model. Our results suggest that COX-2 is involved in CDAA- and TAA-induced liver fibrosis. Our data also indicate that JTE-522 is a potent chemopreventive agent of rat liver fibrosis with low toxicity.
  Gastroenterology 08/2003; 125(2):556-71. · 11.68 Impact Factor
• Article: Total synthesis of the antitumor acetogenin mosin B: desymmetrization approach to the stereodivergent synthesis of threo/trans/erythro-type acetogenins.

  Naoyoshi Maezaki, Naoto Kojima, Atsunobu Sakamoto, Hiroaki Tominaga, Chuzo Iwata, Tetsuaki Tanaka, Morito Monden, Bazarragchaa Damdinsuren, Shoji Nakamori
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  ABSTRACT: A total synthesis of the threo/trans/erythro-type acetogenin mosin B and one of its diastereomers has been achieved. The carbon skeleton is assembled in a convergent fashion from two segments (a THF ring segment and a gamma-lactone segment) through the Nozaki-Hiyama-Kishi reaction. The THF ring segment was stereoselectively constructed by a stereodivergent synthesis starting from a common intermediate (4-cyclohexene-1,2-diol) based on a desymmetrization strategy. The gamma-lactone segment was synthesized by coupling a triflate and a chiral alpha-sulfenyl gamma-lactone. By virtue of these synthetic results, we suggest that the absolute configuration of natural mosin B is 1 a. Antiproliferative effects of 1 a and 1 b were also investigated.
  Chemistry 02/2003; 9(2):389-99. · 5.93 Impact Factor
• Article: Overexpression of MT3-MMP in hepatocellular carcinoma correlates with capsular invasion.

  Isao Arai, Hiroaki Nagano, Motoi Kondo, Hirofumi Yamamoto, Nobuaki Hiraoka, Yurika Sugita, Hideo Ota, Shinichi Yoshioka, Masato Nakamura, Hiroshi Wada, [......], Hitoshi Kato, Shigeru Marubashi, Atsushi Miyamoto, Yutaka Takeda, Keizo Dono, Koji Umeshita, Shoji Nakamori, Kenichi Wakasa, Masato Sakon, Morito Monden
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  ABSTRACT: Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably up-regulated in epithelial cancers and are key agonists of angiogenesis, invasion and metastasis. Recent studies have shown high levels of various MMPs, including MT1-MMP, MMP-1, MMP-2 and MMP-9, and their involvement in tumor progression in human hepatocellular carcinoma (HCC). However, the expression and role of MT3-MMP in HCC remains unclear. We examined the immunohistochemical expression of MT3-MMP in surgically resected HCCs (n=58), hepatitis C virus (HCV) and hepatitis B virus (HBV)-related chronic hepatitis (n=34) and cirrhosis (n=24). MT3-MMP expression was observed in all non-cancerous liver tissues. In HCCs, 52% (30/58) of patients showed high MT3-MMP expression while the remaining 48% (28/58) of patients showed low expression. A clinicopathological survey demonstrated a significant correlation between high MT3-MMP expression and capsular invasion of carcinoma (p = 0.034) although there was no correlation between high MT3-MMP expression in HCC and overall survival or disease-free survival. MT3-MMP was expressed not only in chronic hepatitis and liver cirrhosis, but also in HCC, and high MT3-MMP expression correlated significantly with capsular invasion of carcinoma.
  Hepato-gastroenterology 54(73):167-71. · 0.66 Impact Factor
• Article: Pulmonary mucosa-associated lymphoid tissue type lymphoma with increased accumulation of fluorine 18-fluorodeoxyglucose on positron emission tomography.

  Javzandulam Natsag, Noriyuki Tomiyama, Atsuo Inoue, Thomas J Bryce, Bazarragchaa Damdinsuren, Osamu Honda, Naoki Mihara, Hiromitsu Sumikawa, Shigeki Fujita, Takeshi Johkoh, Jun Hatazawa, Hironobu Nakamura
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  ABSTRACT: Mucosa-associated lymphoid tissue (MALT) type lymphoma has generally been thought not to show increased fluorine 18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET), based on previous research. Only a limited numbers of articles have been published on this topic, however, involving a small number of cases. Although positive FDG PET results might be uncommon in this entity, a case of increased FDG accumulation in a case of MALT type lymphoma of the lung is presented.
  Journal of Computer Assisted Tomography 29(5):640-3. · 1.22 Impact Factor