Tamura, Hiroomi

写真a

Affiliation

Faculty of Pharmacy (Mita)

Position

Professor Emeritus

External Links

Academic Background 【 Display / hide

  • 1978.03

    The University of Tokyo, Faculty of Pharmaceutical Science

    University, Graduated

  • 1983.03

    The University of Tokyo, Graduate School of Pharmaceutical Sciences, Division of Biological Pharmaceutics

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • Doctor of Pharmacy, The University of Tokyo, Coursework, 1983.03

Licenses and Qualifications 【 Display / hide

  • the pharmacist license in Japan

 

Research Areas 【 Display / hide

  • Life Science / Pharmaceutical hygiene and biochemistry (Biological System Pharmaceutical Science)

  • Humanities & Social Sciences / Family and consumer sciences, and culture and living

Research Themes 【 Display / hide

  • Relationship between inhibition of estrogen sulfoconjugation by coffee component and prevention of life-style related dideases by coffee intake., 

    2008
    -
    2010

  • Effects of vitamin C on the conjugation reactions in the human colon carcinoma Caco-2 cells., 

     

  • Induction of neurosteriod biosynthesis in human glial GI-1 cells by retinoic acid., 

     

 

Books 【 Display / hide

  • Dexamethasone Suppresses Neurosteroid Biosynthesis in Human Glial Cells via Cross-Talk with Vitamins A and D. in Horizons in Neuroscience Research. Volume 24

    TAMURA Hiroomi, Nova Science Publishers, 2016.04

    Scope: Chapter 8, pp. 137-148

  • Coffee in Health and Disease Prevention.

    TAMURA Hiroomi, Academic Press, 2014.11

    Scope: Chapter 61. Effects of Coffee on Estrogen Sulfation in Human Colon Carcinoma Caco-2 Cells.

  • コーヒーはお好きですか?.

    田村悦臣., 慶應義塾, 2014.02

  • 薬学領域の食品衛生化学(長澤一樹、川崎直人編).

    田村悦臣., 廣川書店, 東京, 2013.03

    Scope: 37-93

  • 薬学用語辞典.

    田村悦臣., 東京化学同人, 東京, 2012.03

    Scope: 1-449

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Papers 【 Display / hide

  • Methotrexate significantly induces apoptosis by inhibiting STAT3 activation in NPM-ALK-positive ALCL cells.

    Uchihara Y, Komori R, Tago K, Tamura H, Funakoshi-Tago M

    Biochemical pharmacology (Biochemical Pharmacology)  170   113666 2019.12

    Research paper (scientific journal),  ISSN  0006-2952

     View Summary

    © 2019 Elsevier Inc. Anaplastic large cell lymphoma (ALCL) is associated with a characteristic chromosomal translocation that generates the oncogenic fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). Methotrexate is a commonly used chemotherapeutic drug in the treatment of multiple cancers due to its inhibition of dihydrofolate reductase (DHFR), which suppresses the synthesis of DNA. In the present study, we found that low-dose methotrexate significantly induced apoptosis in transformed Ba/F3 cells expressing NPM-ALK by inhibiting the activation of signal transducer and activator of transcription factor 3 (STAT3), a critical downstream molecule of NPM-ALK. Although methotrexate prevented the phosphorylation of STAT3, it did not affect the activity of NPM-ALK. A co-treatment with folinic acid prevented the methotrexate-induced inhibition of STAT3 activation and induction of apoptosis, suggesting that methotrexate exerts its cytotoxic effects by depleting tetrahydrofolate (THF) in transformed cells by NPM-ALK. Furthermore, methotrexate induced the down-regulation of the anti-apoptotic protein, MCL-1, DNA damage, and the activation of a p53 tumor suppressor, leading to apoptosis through the inhibition of STAT3. Methotrexate significantly induced apoptosis in ALK inhibitor-resistant cells expressing the NPM-ALK mutant harboring the point mutation, G262R, and in ALCL patient-derived NPM-ALK-positive Ki-JK cells. Collectively, these results demonstrate the potential therapeutic application of methotrexate, which inhibits the activation of STAT3, to NPM-ALK-positive ALCL.

  • Tyrosine-phosphorylated SOCS3 negatively regulates cellular transformation mediated by the myeloproliferative neoplasm-associated JAK2 V617F mutant

    Funakoshi-Tago M., Tsuruya R., Ueda F., Ishihara A., Kasahara T., Tamura H., Tago K.

    Cytokine (Cytokine)  123   154753 2019.11

    Research paper (scientific journal), Joint Work,  ISSN  10434666

     View Summary

    © 2019 Elsevier Ltd In the majority of myeloproliferative neoplasms (MPNs) patients, a point mutation, V617F has been found in Janus kinase 2 (JAK2) gene, and this JAK2 mutant provoked aberrant signaling pathway. In the current study, we found that suppressor of cytokine signaling proteins 3 (SOCS3) possessed the tumor suppressive activity against the JAK2 V617F mutant-provoked cellular transformation. The knockdown of SOCS3 increased the expression level of the JAK2 V617F mutant, which enhanced the activation of signaling mediators, including signal transducer and activator of transcription 3 and 5 (STAT3, STAT5) and extracellular signal-regulated kinase (ERK), and also increased of the proliferation rate and tumorigenesis activity of Ba/F3 cells expressing the JAK2 V617F mutant and erythropoietin receptor (EpoR). In contrast, the enforced expression of SOCS3 significantly inhibited the JAK2 V617F mutant-induced activation of downstream signaling molecules, cell proliferation, and tumorigenesis by down-regulating the expression level of the JAK2 V617F mutant. SOCS3 interacted with the JAK2V617F mutant through its SH2 domain and was phosphorylated at Tyr-204 and Tyr-221 in its SOC

  • 3D in vivo imaging of the keratin filament network in the mouse stratum granulosum reveals profilaggrin-dependent regulation of keratin bundling

    Usui K., Kadono N., Furuichi Y., Shiraga K., Saitou T., Kawasaki H., Toyooka K., Tamura H., Kubo A., Amagai M., Matsui T.

    Journal of Dermatological Science (Journal of Dermatological Science)  94 ( 3 ) 346 - 349 2019.06

    Research paper (scientific journal), Joint Work,  ISSN  0923-1811

  • N-Acetyl cysteine prevents activities of STAT3 inhibitors, Stattic and BP-1-102 independently of its antioxidant properties.

    Uchihara Y, Ohe T, Mashino T, Kidokoro T, Tago K, Tamura H, Funakoshi-Tago M

    Pharmacological reports : PR (Pharmacological Reports)  71 ( 6 ) 1067 - 1078 2019.05

    Research paper (scientific journal),  ISSN  1734-1140

     View Summary

    © 2019 Institute of Pharmacology, Polish Academy of Sciences Background: Inhibitors for signal transducer and activator of transcription 3 (STAT3), Stattic, BP-1-102, and LLL12 significantly induce apoptosis in transformed Ba/F3 cells expressing an oncogenic fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) that induces the activation of STAT3. We found that the antioxidant reagent, N-acetyl cysteine (NAC) prevented the abilities of Stattic and BP-1-102, but not LLL12 to induce apoptosis in transformed cells expressing NPM-ALK, providing a novel problem in use of STAT3 inhibitors. We herein investigated the mechanisms how NAC prevented the effects of Sttatic and BP-1-102. Methods: Ba/F3 cells expressing NPM-ALK and SUDHL-1 cells were treated with antioxidants such as NAC, Trolox or edaravone in combination with STAT3 inhibitors. Phosphorylation of STAT3, cell proliferation rate, cell viability, cell cycle, internucleosomal DNA fragmentation and the intracellular accumulation of reactive oxygen species (ROS) was investigated. The binding of STAT3 inhibitors and NAC was analyzed by LC–MS. Results: NAC but not Trolox and edaravone diminished the abilities of Stattic and BP-1-102 to induce apoptosis in cells expressing NPM-ALK. The ROS levels in cells expressing NPM-ALK were not markedly affected by the treatments with Stattic and BP-1-102 in combination with NAC, suggesting that NAC inhibited the activity of Stattic and BP-1-102 independent of its antioxidant activity. LC–MS analysis revealed that NAC directly bound to Stattic and BP-1-102. Furthermore, these NAC adducts exhibited no cytotoxicity, and failed to affect the activity of STAT3. Conclusions: NAC antagonizes the activities of Stattic and BP-1-102, which inhibit STAT3 activation by interacting with cysteine residues in STAT3.

  • Coffee brew intake can prevent the reduction of lens glutathione and ascorbic acid levels in HFD-fed animals.

    Nakazawa Y, Ishimori N, Oguchi J, Nagai N, Kimura M, Funakoshi-Tago M, Tamura H

    Experimental and therapeutic medicine 17 ( 2 ) 1420 - 1425 2019.02

    Research paper (scientific journal),  ISSN  1792-0981

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • コーヒーによる認知症予防効果について

    TAMURA Hiroomi

    認知症予防学会 第6回学術講演会 (東京) , 

    2017.02

    Oral presentation (invited, special), 認知症予防学会

  • 5-Hydroxyoxindole誘導体のLPSシグナル経路阻害による抗炎症作用

    TAMURA Hiroomi

    第89回 日本生化学会大会 (仙台) , 

    2016.09

    Poster presentation

  • 本態性血小板血症の原因遺伝子産物JAK2V617F変異体によるTpoRのリン酸化を介した発がん誘導機構

    TAMURA Hiroomi

    第89回 日本生化学会大会 (仙台) , 

    2016.09

    Oral presentation (general)

  • 慢性骨髄増殖性腫瘍に対するメトトレキサートの新しい作用機序

    TAMURA Hiroomi

    第89回 日本生化学会大会 (仙台) , 

    2016.09

    Poster presentation

  • コーヒー成分によるヒト神経芽細胞腫におけるβ-セクレターゼ発現の抑制効果

    TAMURA Hiroomi

    第89回日本生化学会大会 (仙台) , 

    2016.09

    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • タンパク質分解系を介したコーヒー成分による生活習慣病予防の分子メカニズムの解析

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Investigation of molecular basis of preventive effects of coffee consumption on lifestyle-related diseases.

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, TAMURA Hiroomi, Grant-in-Aid for Scientific Research (C), Principal investigator

     View Summary

    It has been reported that habitual coffee intake reduces the risk of developing lifestyle-related diseases associated with obesity and inflammation. We found that the coffee bean roasting ingredient suppresses the differentiation of adipocytes, a risk factor of obesity, by promoting the degradation of the adapter molecule IRS1 of the insulin signaling pathway, using the preadipocyte 3T3-L1 . Regarding the anti-inflammatory effect of coffee, we found that the coffee bean roasting ingredient suppresses the inflammatory response of LPS-induced mouse macrophage cells, and the effect was due to the activation of the transcription factor Nrf2 by promoting the degradation of Keap1. The above results lead to the elucidation of the effect of prevention of lifestyle diseases caused by drinking of coffee on the molecular bases.

  • Effects of coffee consumption on steroid metabolisms linked to life-style related disorders.

    2012.04
    -
    2015.03

    Keio University, TAMURA Hiroomi, Grant-in-Aid for Scientific Research (C), No Setting

     View Summary

    Coffee is one of the world’s most commonly consumed beverages. Recent epidemiological studies show that coffee consumption has been associated with a lower risk of several life-style related disorders such as diabetes, obesity, cancers and dementia. On the other hand, dysfunction of metabolism of steroids such as stress hormone, estrogens and androgens is closely linked to the risk of incidence of these disorders. We investigated effects of coffee on the metabolism of these steroid hormones in human cancer cells such as colon, breast, prostate cancers and glioma. We obtained results suggesting protective effects of coffee on colon and breast cancers but not to prostate cancer. In addition, our result suggest that coffee may increase production of neurosteroids that act to lower the risk of dementia.

  • Study for the correlation between lifestyle-related diseases and the inhibition of estrogen sulfo-conjugation by coffee.

    2009
    -
    2011

    Keio University, TAMURA Hiroomi, Grant-in-Aid for Scientific Research (C), No Setting

     View Summary

    We found that components in roasting coffee strongly inhibit the sulfate conjugation of estrogen in the cell model of human gastrointestinal tract, Caco-2. We hypothesized that this inhibitory effect of coffee on the estrogen sulfation is correlated to the preventive effect of daily coffee consumption on lifestyle-related diseases. To demonstrate this hypothesis, we tried to purify and identify the inhibitory components of coffee. From 1kg decaffeinated instant coffee, we succeeded in purification and identification of the component. The component has a novel nitrogen-containing aromatic structure(MW. 205, C_<11> H_<11> NO_3). We also found that components in coffee affect gene expression of proteins involved in estrogen metabolism(SULT1E1, sulfatase, and BCRP), and analyzed the mechanism underlying the phenomenon.

  • Expression pro filing of drug metabolizing enzymes in human myeloblastic and lymphoid cell lines

    2000
    -
    2001

    Kyoritsu College of Pharmacy, TAMURA Hiro-omi, Grant-in-Aid for Scientific Research (C), No Setting

     View Summary

    To explore the physiological roles of drug-metabolizing enzymes in peripheral blood cells, we examined which isoforms of cytochrome P450 (CYP) and conjugation enzymes (sulfotransferases (SULTs), UDP-glucuronyl transferases (UGT) and glutathione S-transferases (GST)) families were expressed in human myeloid leukemia cell lines (U937, HL-60 and K562) and lymphoid cell lines (BALL-1, MOLT-4 and Jurkat) by RT-PCR. We observed relatively high expression of CYP1A1, CYP1B1, CYP2A6, CYP2A7, CYP2D6, and CYP2E1 in all cell types, but CYP2A13 and CYP2C9 expression was not detected. Expressions of aryl hydrocarbon (Ah) receptor and Ah receptor nuclear translocater (ARNT), which mediate induction of the CYP1 family, were also detected in all cell types. Cell-type specific expression of CYP3A4 and CYP3A5 was observed in MOLT-4 and K562 cells. Weak, but significant, expression of CYP3A7 was detected in K562 cells. We detected expression of SULT1A1, 1A3 and 1C2 in all cell lines although cell-type specific expressions were observed for SULT1B1 (U937 and Jurkat) and SULT2A1 (K562). Expression of UGT1A family, which is known to metabolize many drugs and xenobiotics, was exclusively observed in MOLT-4 and BALL-1. BALL-1 expressed 8 sub families of UGT1A and MOLT-4 expressed 2 UGT1A sub families. All cell lines expressed GSTA4, P1 and T1, however, GSTM1 expression, which is supposed to detoxify carcinogens in cigarette smoke, was detected only in MOLT-4 cells. Oxidative stress (hydroperoxide) induced CYP3A4 and GSTP1 expressions in K562 cells. Chemical inducers (p-naphthoflavone and 3-methylcholanthren) induced CYP1A1 expression in MOLT-4 cells. The profile of drug-metablizing enzymes in the culture cells reported here provides information that furthers our understanding of the physiological roles of drug metabolizing enzymes in human blood cells.

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Awards 【 Display / hide

  • 平成28年度 義塾賞

    2016.11, 慶應義塾, コーヒーの生活習慣病予防効果の分子基盤の解析

    Type of Award: Keio commendation etc.

  • 日本薬学会東海支部学術奨励賞.

    1994.07, 日本薬学会東海支部, Bacillus cereus 由来スフィンゴミエリナーゼの構造と機能の解析

    Type of Award: Award from Japanese society, conference, symposium, etc.

 

Courses Taught 【 Display / hide

  • TOXICOLOGICAL SCIENCES

    2021

  • TOXICOLOGICAL SCIENCES

    2020

  • TOXICOLOGICAL SCIENCES A

    2019

  • TOXICOLOGICAL SCIENCES

    2019

  • STUDY OF MAJOR FIELD: (HYGIENIC CHEMISTRY)

    2019

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Memberships in Academic Societies 【 Display / hide

  • 日本薬学会

     
  • 日本生化学会

     
  • 生薬学会

     
  • 日本神経化学会

     
  • 認知症予防学会

     

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Committee Experiences 【 Display / hide

  • 2015.04
    -
    Present

    代議員, 認知症予防学会

  • 2014.04
    -
    Present

    評議員, 日本生化学会