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Studies on abnormalities of membrane receptor signaling in malignant lymphoma cells as a basis of diagnosis and treatment

Research Project

Project/Area Number 16390103
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionThe University of Tokyo

Principal Investigator

WATANABE Toshiki  The University of Tokyo, Graduate School of Frontier Sciences, Professor, 大学院・新領域創成科学研究科, 教授 (30182934)

Co-Investigator(Kenkyū-buntansha) ISHIDA Takaomi  The University of Tokyo, Graduate School of Frontier Sciences, Research Associate, 大学院・新領域創成科学研究科, 助手 (80293447)
HORIE Ryouichi  Kitasato University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80229228)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordscancer / signal transduction / lymphoma / diagnosis / molecular pathophysiology / CD30 / NF-kB / TRAF protein / HTLV-1 / ATL / DNA microarray / expression profile / Hodgkin lymphoma
Research Abstract

(1)Analysis of CD30 promoter activation :
We demonstrated that the constitutive overexpression CD30 activate ERK1/2 MAPK pathway, and induces JunB expression, which is a common characteristic of neoplastic. Activation of NF-kB results from "ligand-independent activation" of overexpressed CD30 on the Hodgkin/Reed- Sternberg (H-RS) cells, and that inhibition of CD30 signaling by transduction of a dominant negative decoy CD30 that lacks the cytoplasmic region induced apoptotic cell death of H-RS cells (Horie et al., Oncogene 21, 2493, 2002). We showed that cytoplasmic aggregation of TRAF2 and TRAF5 proteins represents constant signaling of CD30 ( Horie et al., Am J Pathol 160, 1647, 2002). We demonstrated that the AP-1 binding sequence located near the microsatellite counteracts the suppressive effects of the microsatellite on the CD30 promoter activity (Watanabe et al., Am J Pathol 163, 633, 2003). We showed that p80NPM-ALK inhibits ligand-independent signal transduction by overexpressed … More CD30 in ALCL cells though sequestration of TRAF proteins in the complex of NPM-ALK and wild type NPM (Horie et al., Cancer Cell 5, 353, 2004).
(2)Expression profile analysis of primary ATL cells :
We characterized the expression profile of primary ATL cells using the synthetic DNA array system and samples of 16 ATL cases and 11 healthy volunteers. The results revealed 108 overexpressed genes and 250 downregulated genes. Based on the results, we are now preparing a detection system of ATL cells in the PBMC using multiple real-time PCR analysis of samples. A pilot study clearly detected ATL cells in a sample derived from a carrier considered to be an asymptomatic carrier, which was confirmed by monoclonal pattern in subsequent Southern blot analysis.
(3)Studies on the target genes of NF-kB :
Expression profile analyses were done by CodeLink system using cell lines with constitutive activation of NF-kB and treatment by DHMEQ. The results revealed more than 1,000 genes that are up- or down-regulated more than two-fold by DHMEQ treatment. Up-regulated genes included these involved in proapoptotic function, and down-regulated genes included those involved in anti-apoptotic function. Furthermore, many genes were revealed to be target genes of NF-kB signaling (a part of these data were used in the manuscript of BLOOD 106, 2642, 2005).
(4)Basic studies on the molecular targeted therapy by NF-kB inhibition using DHMEQ :
Anti-tumor activity of DHMEQ against ATL, CLL and Hodgkin's lymphoma was tested by in vitro experiments and in vivo xenograft model using a SCID mice system. As to ATL, DHMEQ was shown to be able to purge carrier's PBMC of HTLV-1-infected but not transformed cells (BLOOD 106, 2642, 2005). DHMEQ was also effective against CLL cells, and showed synergistic effect with fludarabine when used in combination (Leukemia 20, 800, 2006). DHMEQ showed anti-tumor activity against H-RS cells in vitro and in vivo (Cancer Res, submitted). Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (51 results)

All 2006 2005 2004 Other

All Journal Article (51 results)

  • [Journal Article] In vitro and in vivo antitumor activity of the NF-kB inhibitor DHMEQ in the human T-cell leukemia virus type I-transformed cell line, HUT-1022006

    • Author(s)
      Ohsugi T et al.
    • Journal Title

      Leuk Res 30

      Pages: 90-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transactivation of the ICAN-1 gene by CD30 in Hodgkin's Lymphoma.2006

    • Author(s)
      Uchihara JN et al.
    • Journal Title

      Int J Cancer 118

      Pages: 1098-1107

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SUV39HI interacts with HTLV-1 Tax and abrogated Tax transactivation of HTLV-1 LTR2006

    • Author(s)
      Kamoi K et al.
    • Journal Title

      Retrovirology 2 (epub)

      Pages: 5-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DHMEQ, a new NF-kB inhibitor induces apoptosis of chronic lymphocytic leukemia cells and enhances effect of fludarabine2006

    • Author(s)
      Horie R et al.
    • Journal Title

      Leukemia 20

      Pages: 800-806

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vitro and in vivo antitumor activity of the NF-kB inhibitor DHMEQ in the human T-cell leukemia virus type I-transformed cell line, HUT-1022006

    • Author(s)
      Ohsugi T, Kumasaka T, Ishida A, Ishida T, Horie R, Watanabe T, Umezawa K, Yamaguchi K.
    • Journal Title

      Leuk Res 30

      Pages: 90-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hodgkin's lymphoma cells are efficiently engrafted and expressed tumor marker CD30 with constitutive NF-kB activity in unconditioned NOD-SCID/gcnull (NOG) mice2006

    • Author(s)
      Dewan Md.Z, Watanabe M, Ahmed S, Terashima K, Horiuchi S, Sata T, Honda M, Ito M, Watanabe T, Horie R, Yamamoto N.
    • Journal Title

      Cancer Sci 96

      Pages: 466-473

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transactivation of the ICAM-1 gene by CD30 in Hodgkin's Lymphoma.2006

    • Author(s)
      Uchihara JN, Matsuda T, Okudaira T, Ishikawa C, Masuda M, Horie R, Watanabe T, Ohta T, Takasu N, Mori N.
    • Journal Title

      Int J Cancer 118

      Pages: 1098-1107

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SUV39H1 interacts with HTLV 1 Tax and abrogates Tax transactivation of HTLV- 1 LTR2006

    • Author(s)
      Kamoi K, Yamamoto K, Misawa A, Miyake A, Ishida T, Tanaka Y, Mochizuki M, Watanabe T
    • Journal Title

      Retrovirology 3(epub)

      Pages: 5-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DHMEQ, a new NF-kB inhibitor induces apoptosis of chronic lymphocytic leukemia cells and enhances effect of fludarabine2006

    • Author(s)
      Horie R, Watanabe M, Okamura T, Taira M, Higashihara M, Watanabe T, Umezawa K
    • Journal Title

      Leukemia 20

      Pages: 800-806

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intraocular soluble IL-2 receptor alpha in a patient with adult T-cell Leukemia with intraocular invasion2006

    • Author(s)
      Sugita S
    • Journal Title

      Br J Ophthalmol (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DHMEQ, a new NF-κB inhibitor induces apoptosis of chronic lymphocytic leukemia cells and enhances effect of fludarabine2006

    • Author(s)
      Horie R
    • Journal Title

      Leukemia (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR2006

    • Author(s)
      Kamoi K
    • Journal Title

      Retrovirology 3(Epub)

      Pages: 5-5

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transactivation of the ICAM-1 gene by CD30 in Hodgkin's Lymphoma.2006

    • Author(s)
      Uchihara JN
    • Journal Title

      Int J Cancer 118

      Pages: 1098-1107

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vitro and in vivo antitumor activity of the NF-κB inhibitor DHMEQ in the human T-cell leukemia virus type I。 V transformed cell line, HUT-1022006

    • Author(s)
      Ohsugi T
    • Journal Title

      Leukemia Res 30

      Pages: 90-97

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel NF-kB inhibitor DHMEQ selectively targets constitutive NF-kB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo2005

    • Author(s)
      Watanabe et al.
    • Journal Title

      Int J Cancer 114

      Pages: 32-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L)2005

    • Author(s)
      Iwata et al.
    • Journal Title

      Oncogene 24

      Pages: 1262-1271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The clonal expansion of HTLV-1 infected cells : A comparison between seroconverters and long-term carriers2005

    • Author(s)
      Tanaka et al.
    • Journal Title

      J Inf Dis 191

      Pages: 1140-1147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aberrant NF-□B2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts2005

    • Author(s)
      Nonaka et al.
    • Journal Title

      Oncogene 24

      Pages: 3976-3986

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo Antitumor Activity of the NF-□B Inhibitor Dehydroxymethylepoxyquinomicin in a Mouse Model of Adult T-cell Leukemia2005

    • Author(s)
      Ohsugi T et al.
    • Journal Title

      Carcinogenesis 26

      Pages: 1382-1388

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated expression of CD30 in adult T-cell leukemia cell lines : possible role in constitutive NF-kB activation2005

    • Author(s)
      Higuchi M et al.
    • Journal Title

      Retrovirology 2 (epub)

      Pages: 29-29

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dual targeting of transformed and untransformed HTLV-1-infected T-cells by DHMEQ, a potent and selective inhibitor of NF-kB, as a strategy for chemoprevention and therapy of adult T cell leukemia2005

    • Author(s)
      Watanabe M et al.
    • Journal Title

      BLOOD 106

      Pages: 2462-2471

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] JunB induced by constitutive DC30-ERK1/2 MAPK signaling activates the CD30 promoter in anaplastic large cell lymphoma and Reed-Sternberg cells of Hodgkin lymphoma2005

    • Author(s)
      Watanabe M et al.
    • Journal Title

      Cancer Res 65

      Pages: 7628-7634

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hodgkin's lymphoma cells are efficiently engrafted and expressed tumor marker CD30 with constitutive NF-kB activity in unconditioned NOD-SCID/genull (NOG) mice2005

    • Author(s)
      Dewan Md.Z et al.
    • Journal Title

      Cancer Sci 96

      Pages: 466-473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel NF-kB inhibitor DHMEQ selectively targets constitutive NF-kB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo2005

    • Author(s)
      Watanabe M, Dewan Z, Okamura T, Sasaki M, Itoh K, Higashihara M, Mizoguchi H, Honda M, Sata T, Watanabe T, Yamamoto N, Umezawa K, Horie R
    • Journal Title

      Int J Cancer 114

      Pages: 32-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HTLV-I Tax induces associates with Crk-associated substrate lymphocyte type (Cas-L)2005

    • Author(s)
      Iwata S, Souta-Kuribara A, Sasaki T, Kobayashi H, Yamakawa A, Hosono O, Kawasaki H, Tanaka H, Dang NH, Watanabe T, Arima N, Yamaoka S, Morimoto C
    • Journal Title

      Oncogene 24

      Pages: 1262-1271

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The clonal expansion of HTLV- 1 infected cells : A comparison between seroconverters and long-term carriers2005

    • Author(s)
      Tanaka G, Okayama A, Watanabe T, Aizawa S, Stuver S, Mueller N, Hsieh C-C, Tsubouchi H
    • Journal Title

      J Inf Dis 191

      Pages: 1140-1147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aberrant NF-kB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts2005

    • Author(s)
      Nonaka M, Horie R, Itoh K, Watanabe T, Yamamoto N, Yamaoka S.
    • Journal Title

      Oncogene 24

      Pages: 3976-3986

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo Antitumor Activity of the NF-_B Inhibitor Dehydroxymethylepoxy-quinomicin in a Mouse Model of Adult T-cell Leukemia2005

    • Author(s)
      Ohsugi T, Horie R, Kumasaka T, Ishida A, Ishida T, Yamaguchi K, Watanabe T, Umezawa K, Urano T
    • Journal Title

      Carcinogenesis 26

      Pages: 1382-1388

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated expression of CD30 in adult T-cell leukemia cell lines : possible role in constitutive NF-kB activation2005

    • Author(s)
      Higuchi M, Matsuda T, Mori N, Yamada Y, Horie R, Watanabe T, Takahashi M, Oie M, Fujii M
    • Journal Title

      Retrovirology 2(epub)

      Pages: 29-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dual targeting of transformed untransformed HTLV- 1-infected T-cells by DHMEQ, a potent and selective inhibitor of NF-kB, as a strategy for chemoprevention and therapy of adult T cell leukemia2005

    • Author(s)
      Watanabe M, Ohsugi T, Shoda M, Ishida T, Aizawa S, Maruyama-Nagai M, Utsunomiya A, Koga S, Yamada Y, Kamihira S, Okayama A, Kikuchi H, Uozumi K, Yamaguchi K, Higashihara M, Umezawa K, Watanabe T, Horie R
    • Journal Title

      BLOOD 106

      Pages: 2462-2471

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] JunB induced by constitutive CD30-ERK1/2 MAPK signaling activates the CD30 promoter in anaplastic large cell lymphoma and Reed-Sternberg cells of Hodgkin lymphoma2005

    • Author(s)
      Watanabe M, Sasaki M, Itoh K, Higashihara M, Umezawa K, Kadin ME, Abraham LJ, Watanabe T, Horie R.
    • Journal Title

      Cancer Res 65

      Pages: 7628-7634

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated expression of CD30 in adult T-cell leukemia cell lines : possible role in constitutive NF-κB activation2005

    • Author(s)
      Higuchi M
    • Journal Title

      Retrovirology 2(Epub)

      Pages: 29-29

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hodgkin's Lymphoma cells are efficiently engrafted and expressed tumor marker CD30 with constitutive NF-κB activity in unconditioned NOD-SCID/gcnull (NOG) mice2005

    • Author(s)
      Dewan Md.Z
    • Journal Title

      Cancer Sci 96

      Pages: 466-473

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dual targeting of transformed and untransformed HTLV-1-infected T-cells by DHMEQ, a potent and selective inhibitor of NF-κB, as a strategy for chemoprevention and therapy of adult T cell leukemia2005

    • Author(s)
      Watanabe M
    • Journal Title

      BLOOD 106

      Pages: 2462-2471

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vivo antitumor activity of the NF-κB inhibitor Dehydroxymethylepoxy-quinomicin in a mouse model of adult T-cell leukemia2005

    • Author(s)
      Ohsugi T
    • Journal Title

      Carcinogenesis 26

      Pages: 1382-1388

    • Related Report
      2005 Annual Research Report
  • [Journal Article] JunB induced by constitutive CD30-ERK1/2MAPK signaling activates the CD30 promoter in anaplastic large cell lymphoma and Reed-Sternberg cells of Hodgkin lymphoma2005

    • Author(s)
      Watanabe M
    • Journal Title

      Cancer Res 65

      Pages: 7628-7634

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel NF-κB inhibitor DHMEQ selectively targets constitutive NF-κB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo2005

    • Author(s)
      Watanabe M
    • Journal Title

      Int J Cancer 114

      Pages: 32-38

    • Related Report
      2005 Annual Research Report
  • [Journal Article] HTLV-I-Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L)2005

    • Author(s)
      Iwata S
    • Journal Title

      Oncogene 24

      Pages: 1262-1271

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant NF-κB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts2005

    • Author(s)
      Nonaka M
    • Journal Title

      Oncogene 24

      Pages: 3976-3986

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The clonal expansion of HTLV-1 infected cells : A comparison between seroconverters and long-term carriers2005

    • Author(s)
      Tanaka G
    • Journal Title

      J Inf Dis 191

      Pages: 1140-1147

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant NF-kB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts2005

    • Author(s)
      Nonaka M, Horie R, Itoh K, et al.
    • Journal Title

      Oncogene (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The clonal expansion of HTLV-1 infected cells : A comparison between seroconverters and lone-term carriers2005

    • Author(s)
      Tanaka G, Okayama A, Watanabe T, et al.
    • Journal Title

      J Inf Dis (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] HTLV-1 Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L)2005

    • Author(s)
      Iwata S, Souta-Kuribara A, Sasaki T et al.
    • Journal Title

      Oncogene 24

      Pages: 1262-1271

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel NF-кB inhibitor DHMEQ selectively targets constitutive NF-кB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo2005

    • Author(s)
      Watanabe M, Dewan Z, Okamura T et al.
    • Journal Title

      Int J Cancer 114

      Pages: 32-38

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rapid Tumor Death Model for Evaluation of New Therapeutic Agents for Adult T-cell Leukemia2004

    • Author(s)
      Ohsugi et al.
    • Journal Title

      Lab Invest 84

      Pages: 263-266

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ubiquitination-dependent translocation of TRAF2 to the insoluble cellular fraction is required for its activation of JNK but not of p38 or NF-□B.2004

    • Author(s)
      Habelhah H wt al.
    • Journal Title

      EMBOJ 23

      Pages: 322-332

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid Tumor Death Model for Evaluation of New Therapeutic Agents for Adult T-cell Leukemia2004

    • Author(s)
      Takeo Ohsugi, Kazunari Yamaguchi, Toshio Kumasaka, Takaomi Ishida, Ryouichi Horie, Toshiki Watanabe, Noboru Sakio, Toshio Fujimoto, Noriyuki Sakamoto, Toru Urano
    • Journal Title

      Lab Invest 84

      Pages: 263-266

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ubiquitination-dependent translocation of TRAF2 to the insoluble cellular fraction is required for its activation of JNK but not of p38 or NF-kB.2004

    • Author(s)
      Habelhah H, Takahashi S, Cho SG, Kadoya T, Watanabe T, Ronai Z
    • Journal Title

      EMBO J 23

      Pages: 322-332

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prompt tumor formation and maintenance of constitutive NF-kappaB activity of multiple myeloma cells in NOD/SCID/gammacnull mice.2004

    • Author(s)
      Dewan MZ, Watanabe M, Terashima K, et al.
    • Journal Title

      Cancer Sci 95

      Pages: 564-568

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intraocular soluble IL-2 receptor alpha in a patient with adult T-cell Leukemia with intraocular invasion

    • Author(s)
      Sugita S et al.
    • Journal Title

      Br J Ophthalmol (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intraocular soluble IL-2 receptor alpha in a patient with adult T-cell Leukemia with intraocular invasion

    • Author(s)
      Sugita S, Takase H, Yoshida T, Sugamoto Y, Watanabe T, Mochizuki M.
    • Journal Title

      Br J Ophthalmol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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