Hirokuni Taguchi

Kochi University, Kôti, Kōchi, Japan

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Publications (286)1588.76 Total impact

  • Makoto Kobayashi · Tetsuya Kubota · Yoshiki Uemura · Hirokuni Taguchi
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    ABSTRACT: Chronic cough is caused by a wide variety of disease conditions, including asthma, rhino-sinusitis and gastro-oesophageal reflux. We describe the case of a 42-year-old man with hypereosinophilic syndrome presenting with chronic dry cough. The cough did not respond to inhaled corticosteroid or leucotriene receptor antagonists. Hepatosplenomegaly was noted and the patient became anaemic and thrombocytopenic. He was refractory to treatment with hydroxyurea and interferon-alpha. Administration of imatinib resulted in complete resolution of eosinophilia and cough, without the use of anti-asthma drugs. Analysis of RNA from this patient demonstrated expression of the Fip1-like 1/platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) fusion gene. The myeloproliferative variant of hypereosinophilic syndrome may cause chronic intractable cough, and a trial of imatinib treatment may be warranted.
    Respirology 02/2009; 14(2):302-4. DOI:10.1111/j.1440-1843.2008.01467.x · 3.35 Impact Factor
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease with a poor prognosis in which nuclear factor kappa B (NF-kappaB) is thought to play a role. This study explored the effects of histone deacetylase inhibitors (HDACIs) MS-275, suberoylanilide hydroxamic acid (SAHA), and LBH589 on both human T-cell lymphotropic virus type I (HTLV-1)-infected T cells (MT-1, -2, -4, and HUT102) and freshly isolated ATL cells harvested from patients. HDACIs effectively inhibited the proliferation of these cells. For example, MS-275, SAHA, and LBH589 effectively inhibited the proliferation of MT-1 cells with ED(50s) of 6microM, 2.5microM, and 100nM, respectively, as measured by 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on day 2 of culture. In addition, HDACIs induced cell cycle arrest at the G2/M phase and apoptosis of HTLV-1-infected T-cells in conjunction with regulation of apoptosis-related proteins. Electrophoretic mobility shift assay showed that exposure of HTLV-1-infected T-cells to HDACIs for 48h inhibited formation of the NF-kappaB/DNA binding complex. Moreover, we found that HDACIs accumulated NF-kappaB and inhibitory subunit of NF-kappaB in the cytoplasm in conjunction with the down-regulation of NF-kappaB in the nucleus, suggesting that HDACIs blocked nuclear translocation of NF-kappaB. Based on these findings, we believe HDACIs can be useful for treating patients with ATL or other types of cancer in which NF-kappaB plays a role.
    Leukemia Research 03/2008; 32(2):287-96. DOI:10.1016/j.leukres.2007.05.026 · 2.35 Impact Factor
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    ABSTRACT: Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation.
    Blood 10/2007; 110(6):2034-40. DOI:10.1182/blood-2007-02-073700 · 10.45 Impact Factor
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    ABSTRACT: PC-SPES is an eight-herb mixture that has an activity against prostate cancer. Recently, we purified Saw Palmetto (Serenoa repens) from PC-SPES and found that Saw Palmetto induced growth arrest of prostate cancer LNCaP, DU145, and PC3 cells with ED50s of approximately 2.0, 2.6, and 3.3 microl/ml, respectively, as measured by mitochondrial-dependent conversion of the the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Saw Palmetto induced apoptosis of LNCaP cells in a time- and dose-dependent manner as measured by TUNEL assays. Also, Saw Palmetto increased the expression of p21waf1 and p53 protein in LNCaP cells. In addition, we found that Saw Palmetto down-regulated DHT- or IL-6-induced expression of prostate specific antigen in conjunction with down-regulation of the level of androgen receptor in the nucleus as measured by Western blot analysis. Moreover, Saw Palmetto down-regulated the IL-6-induced level of the phosphorylated form of STAT 3 in LNCaP cells. Furthermore, Saw Palmetto inhibited the growth of LNCaP cells present as tumor xenografts in BALB/c nude mice without adverse effect. These results indicate that Saw Palmetto might be useful for the treatment of individuals with prostate cancer.
    International Journal of Oncology 10/2007; 31(3):593-600. DOI:10.3892/ijo.31.3.593 · 3.03 Impact Factor
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    ABSTRACT: Cancer-associated retinopathy (CAR) is a rare paraneoplastic disorder that is frequently found in patients with small cell lung cancer (SCLC); it is caused by autoantibody to the 23-kDa photoreceptor protein, recoverin. We report a 9-year survivor of SCLC after concurrent chemoradiotherapy. His anti-recoverin antibody remains positive. Long-term survival without SCLC recurrence might be related to an autoimmunity mechanism that causes CAR due to the presence of anti-recoverin antibody cross-reacting with retinal cells and tumor cells. The current literature review was conducted to evaluate the impact on overall survival according to anti-recoverin antibody status.
    Lung Cancer 09/2007; 57(3):399-403. DOI:10.1016/j.lungcan.2007.02.015 · 3.96 Impact Factor
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    ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
    Leukemia 07/2007; 21(6):1308-10. DOI:10.1038/sj.leu.2404647 · 10.43 Impact Factor
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    ABSTRACT: The Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. Aberrant expression of these kinases occurs in solid tumors and is associated with aneuploidy and carcinogenesis. We found in this study that Aurora kinase A and B were aberrantly expressed in a variety of types of human leukemia cell lines (n = 15, e.g., PALL-1, PALL-2, HL-60, NB4, MV4-11, etc.), as well as freshly isolated leukemia cells from individuals with acute myelogenous leukemia (n = 44) compared with bone marrow mononuclear cells from healthy volunteers (n = 11), as measured by real-time PCR. ZM447439 is a novel selective Aurora kinase inhibitor. The compound induced growth inhibition, caused accumulation of cells with 4N/8N DNA content, and mediated apoptosis of human leukemia cells as measured by thymidine uptake, cell cycle analysis, and annexin V staining, respectively. Especially profound growth inhibition occurred with the PALL-1 and PALL-2 cells, which possess wild-type p53 gene. In contrast, ZM447439 did not inhibit clonogenic growth of myeloid committed stem cells harvested from healthy normal volunteers. Taken together, inhibition of Aurora kinases may be a promising treatment strategy for individuals with leukemia.
    Molecular Cancer Therapeutics 07/2007; 6(6):1851-7. DOI:10.1158/1535-7163.MCT-07-0067 · 5.68 Impact Factor
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    ABSTRACT: We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.
    Lung Cancer 07/2007; 56(3):319-26. DOI:10.1016/j.lungcan.2007.01.030 · 3.96 Impact Factor
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    ABSTRACT: We describe a patient with aggressive lymphoma who contracted an ethmoidal sinus infection due to Exserohilum rostratum after non-myeloablative allogeneic peripheral blood stem cell transplantation. E. rostratum is an extremely rare causative pathogen of invasive fungal infection. Phylogenetic tree analysis of the D1/D2 domains within the LSU rDNA identified the molecular structure of isolates. We believe this is the first description of E. rostratum infection in a patient who underwent hematopoietic stem cell transplantation.
    Transplant Infectious Disease 07/2007; 9(2):137-41. DOI:10.1111/j.1399-3062.2007.00212.x · 2.06 Impact Factor
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    ABSTRACT: Bone morphogenetic proteins (BMP), belonging to the transforming growth factor-beta superfamily, are important regulators of cell growth, differentiation, and apoptosis. The biological effects of BMPs on malignant lymphoma, however, remain unknown. Promoter methylation of the BMP-6 gene in lymphomas was investigated. We investigated BMP-6 promoter methylation and its gene expression in various histologic types of 90 primary lymphomas and 30 lymphoma cell lines. The effect of BMP-6 promoter hypermethylation on clinical outcome was also evaluated. BMP-6 was epigenetically inactivated in subsets of lymphomas. The silencing occurred with high frequency in diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma in association with aberrant BMP-6 promoter methylation. The methylation was observed in 60% (21 of 35) of DLBCL cases and 100% (7 of 7) of DLBCL cell lines, and in 83% (5 of 6) of Burkitt's lymphoma cases and 86% (12 of 14) of Burkitt's lymphoma cell lines. In contrast, other histologic types of primary lymphomas studied had little or no detectable methylation (1 of 49; 2%). The presence of BMP-6 promoter hypermethylation in DLBCL statistically correlated with a decrease in disease-free survival (P = 0.014) and overall survival (P = 0.038). Multivariate analysis showed that the methylation profile was an independent prognostic factor in predicting disease-free survival (P = 0.022) and overall survival (P = 0. 046). BMP-6 promoter was hypermethylated more often in aggressive types of lymphomas, and the hypermethylation is likely to be related to the histologic type of lymphomas. BMP-6 promoter methylation may be a potential new biomarker of risk prediction in DLBCL.
    Clinical Cancer Research 07/2007; 13(12):3528-35. DOI:10.1158/1078-0432.CCR-06-2766 · 8.72 Impact Factor
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    C Nishioka · T Ikezoe · J Yang · H P Koeffler · H Taguchi
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease in which the human T-cell lymphotropic virus type I (HTLV-I) has been recognized as the etiologic agent. Fludarabine is a purine analog that has demonstrated significant activity in B-cell malignancies, including chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma. This study explored the effects of fludarabine on HTLV-1-infected T cells (MT-1, -2, -4 and HUT102). Fludarabine induced growth arrest and apoptosis of these cells, as measured by 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle analysis and annexin V staining. Moreover, exposure of HTLV-1-infected T cells to fludarabine decreased the levels of X-inhibitor of apoptosis protein in conjunction with inhibition of nuclear factor kappaB (NF-kappaB)/DNA-binding activity, as measured by Western blot analysis and electrophoretic mobility shift and reporter gene assays, respectively. Further studies found that fludarabine accumulated NF-kappaB and inhibitory subunit of NF-kappaB in cytosole in conjunction with downregulation of NF-kappaB in nucleus, suggesting that fludarabine blocked nuclear translocation of NF-kappaB. Taken together, fludarabine may be useful for treatment of individuals with ATL and other types of cancer in which NF-kappaB plays a role.
    Leukemia 06/2007; 21(5):1044-9. DOI:10.1038/sj.leu.2404622 · 10.43 Impact Factor
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    ABSTRACT: This study found that phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling was activated in human T-cell lymphotropic virus type I (HTLV-1)-infected leukemia cells. Rapamycin (1-100 nM, 48h), the inhibitor of mTOR and its analog RAD001 (1-100 nM, 48 h)-induced growth inhibition and G0/G1 cell cycle arrest of these cells in association with de-phosphorylation of p70S6K and 4E-BP-1, although IC50 was not achieved. Paradoxically, rapamycin-stimulated phosphorylation of Akt at Ser473. Blockade of Akt signaling by the PI3K inhibitor LY294002 (1-20 microM, 48 h) also resulted in the growth inhibition and G0/G1 cell cycle arrest of HTLV-1-infected cells, with IC50 ranging from 5 to 20muM, and it caused de-phosphorylation of p70S6K and 4E-BP-1. Of note, when rapamycin was combined with LY294002, rapamycin-induced phosphorylation of Akt was blocked, and the ability of rapamycin to induce growth arrest of HTLV-1-infected T-cells and suppress the p-p70S6K and p-4E-BP-1 proteins was potentiated. Moreover, both LY294002 and rapamycin down-regulated the levels of c-Myc and cyclin D1 proteins in these cells, and their combination further decreased levels of these cell cycle-regulating proteins. Taken together, longitudinal inhibition of PI3K/Akt/mTOR signaling represents a promising treatment strategy for individuals with adult T-cell leukemia.
    Leukemia Research 06/2007; 31(5):673-82. DOI:10.1016/j.leukres.2006.08.001 · 2.35 Impact Factor
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    ABSTRACT: We examined the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the lung cancer cell lines PC-9, LA-1 and A549. In addition, we examined if the effects of the cytokines on the cell lines are mediated by activation of cyclooxygenase (COX)-2. The three cell lines did not constitutively produce either G-CSF or GM-CSF. G-CSF did not influence cell growth in the three cell lines, while GM-CSF increased cell growth in the A549 and LA-1 lines. G-CSF and GM-CSF dose-dependently decreased cell death in the three cell lines. RT-PCR demonstrated GM-CSF receptor expression in the three lung cancer cell lines, whereas the G-CSF receptor exists only in the PC-9 line. We suggest that G-CSF might rescue the tumor cells from cytotoxicity due to serum deprivation through cellular pathways independent of the G-CSF receptor. G-CSF and GM-CSF increased cyclooxygenase-2 (COX-2) expression in PC-9 and LA-1 cells whereas they decreased COX-2 expression in A549 cells. The COX-2 inhibitor NS-398 increased cell death in PC-9 and LA-1 cells, whereas it decreased cell death in A549 cells. PC-9 and LA-1 clones transfected with sense G-CSF- or GM-CSF showed an increase in COX-2 expression, while COX-2 expression was decreased in transfected A549 clones. COX-2 expression was increased in anti-sense G-CSF- and GM-CSF-transfected A549 clones. Thus, although COX-2 activation seems to induce different biological behavior depending on the cell type, we propose that G-CSF and GM-CSF might accelerate tumor progression by directly regulating COX-2 expression, independently of an autocrine mechanism.
    Oncology Reports 05/2007; 17(4):955-61. DOI:10.3892/or.17.4.955 · 2.30 Impact Factor
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    ABSTRACT: In order to determine the fine-structural differences and labeling by immunoferritin parti- cles of CD4-positive (CD4+) and CD8 positive (CD8+) cells at the ultrastructural level, short-term-cultured lymphocytes from eight healthy donors seropositive for HTLV-I were examined and virus production was examined in vitro. Sera of eight donors were all positive on the particle agglutination (PA) test, but only of the four of the eight were positive on the immunofluorescence (IF) test. Sera with high titer on the PA test, e. g., above 26, were likely to be positive on the IF test, as well. Ultrastructurally, CD4 + cells were mostly smaller than CD8 + cells, with higher N/C ratio and a heterochromatin-rich nucleus. CD8+ cells were usually more abundant in cytoplasmic organelles than CD4 + cells. Interestingly, in CD4+ cells, two types of surface immunofer- ritin labeling were observed, light or slightly heavy segmental in pattern, though CD8 + cells were always labeled in dense, heavy segmental fashion, when antibodies were applied to short-term-cultured fresh lymphocytes. In three of eight cases, only a small number of virus particles were detected in the specimens. These findings demonstrated that labeling of CD4+ and CD8+ cells with each CD4 or CD8 antigen differed, as did the ultrastructural findings for these cells. Further investigation of these differences is needed using other types of markers, such as those for chemokine recep- tors, and other methods to clearly determine the differences between the two types of lym- phocytes in fine structure and how these relate to their functions.
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    ABSTRACT: Epigenetic events are a critical factor contributing to cancer development. The purpose of this study was to identify tumor suppressor genes silenced by DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC). We used microarray analysis to screen for tumor suppressor genes. We identified Per1, a core circadian gene, as a candidate tumor suppressor in lung cancer. Although Per1 levels were high in normal lung, its expression was low in a large panel of NSCLC patient samples and cell lines. Forced expression of Per1 in NSCLC cell lines led to significant growth reduction and loss of clonogenic survival. Recent studies showed that epigenetic regulation, particularly histone H3 acetylation, is essential for circadian function. Using bisulfite sequencing and chromatin immunoprecipitation, we found that DNA hypermethylation and histone H3 acetylation are potential mechanisms for silencing Per1 expression NSCLC. These results support the hypothesis that disruption of circadian rhythms plays an important role in lung tumorigenesis. Moreover, our findings suggest a novel link between circadian epigenetic regulation and cancer development.
    Clinical Cancer Research 04/2007; 13(5):1399-404. DOI:10.1158/1078-0432.CCR-06-1730 · 8.72 Impact Factor
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    ABSTRACT: We describe a 27-year-old man with hypereosinophilc syndrome (HES) presenting acute abdomen due to acute thrombosis of the mesenteric artery, who had a past history of eosinophilic pneumonia followed by multiple arterial thromboses of the extremities. At the recurrence of eosinophilia, he was treated with high-dose corticosteroids. Immediately after the reduction of peripheral blood eosinophils, he suddenly developed perforation of the intestine due to acute thromboses of mesenteric arteries despite sustained anticoagulation therapy. Molecular analysis demonstrated that the FIP1L1-PDGFRA fusion gene was negative. Histopathology showed thrombi and eosinophilic inflammation of arteries. It is important to recognize that HES could be a cause of acute abdomen.
    Internal Medicine 02/2007; 46(10):675-8. DOI:10.2169/internalmedicine.46.6309 · 0.90 Impact Factor
  • Isao Miyoshi · Yoshiki Uemura · Hiroshi Sonobe · Hirokuni Taguchi
    Internal Medicine 02/2007; 46(1):65-6. DOI:10.2169/internalmedicine.46.6232 · 0.90 Impact Factor
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    Internal Medicine 02/2007; 46(8):529-30. DOI:10.2169/internalmedicine.46.6103 · 0.90 Impact Factor
  • Internal Medicine 02/2007; 46(7):429-30. DOI:10.2169/internalmedicine.46.6385 · 0.90 Impact Factor
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    ABSTRACT: A 39 year-old Japanese man who had been treated for pleuritis developed a tumor in the left lung and was admitted to our hospital. Although evidence of tuberculous pleurisy was not proved medically, he had been treated successfully with antituberculous drugs for 9 months. Two months after completion of antituberculous therapy, his X-ray showed a tumor shadow close to his left hilum. A computed tomography (CT) scan showed a left lung tumor with a diameter of 3.3cm, atelectasis in an ajacent field, and no effusion. Tumor markers targeted for lung cancer remained within normal range. Bronchofiberscopy demonstrated a polypoid tumor from left upper lobe bronchus. The pathological examination of CT guided percutaneous biopsy (CTGB) specimen revealed undifferentiated malignant tumor. A pulmonary angiogram disclosed almost complete obstruction of left pulmonary artery. He underwent total pneumonectomy of the left lung, and the final pathological diagnosis of pulmonary artery sarcoma was made. He received neither chemotherapy nor radiotherapy. He is well and disease free 3 years after resection. Surgical resection may improve the prognosis of this malignancy.
    02/2007; 45(1):65-70.

Publication Stats

4k Citations
1,588.76 Total Impact Points


  • 2004–2009
    • Kochi University
      • • Department of Hematology and Respiratory Medicine
      • • Division of Medicine
      Kôti, Kōchi, Japan
  • 2007
    • Kawasaki Medical University
      Kurasiki, Okayama, Japan
  • 1980–2007
    • Kochi Medical School
      Kôti, Kōchi, Japan
  • 2003
    • Cedars-Sinai Medical Center
      • Division of Hematology and Oncology
      Los Angeles, CA, United States
  • 2002
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
  • 2000
    • Okayama University
      • Medical School
      Okayama, Okayama, Japan