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Mechanism of the treatment resistance in DLBCL according to Skp2 expression.

Research Project

Project/Area Number 22790363
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionKurume University

Principal Investigator

SEKI Ritsuko  久留米大学, 医学部, 助教 (50446077)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞 / 組織 / 遺伝子 / 蛋白質 / 細胞・組織
Research Abstract

Using the frozen tissues which confirmed Skp2 protein expression, I performed microarray analysis and went to the cluster ring. Skp2 identified that it was an independent prognostic factor as (GC, ABC type) by the cell origin by array analysis than Lymphochip information. Furthermore, I extract a gene in acknowledgment of significant differenceby limma analysis. Furthermore, IPA(Ingenuity pathway analysis) showed clearly thenetwork composed of cell cycle regulators. Several genes related to cyclins and cell cycle regulation and to the MAPK, WNT, and Myc mediated apoptosis signaling pathways were altered in DLBCLs when compared with Skp2 levels. Skp2 gene and MTA3 gene showed a positive correlation and made clear that it was important to B-cell differentiation for the first time. Furthermore, as a result of extracting 20 genes from a candidate gene more, and having analyzed it by the Real time PCR method, it became clear that both Myc and MTA3 were significantly higher than Skp2 o w expression group in the Skp2 high expression group.It was revealed that not only I broke down restraint molecules mainly in cell cycles suchas p27, but also the Skp2 high expression participated in cell differentiation, and proliferation. I was able to confirm other Myc-related gene reinforcement, too.Additional biochemical and functional in vitro studies are needed to determine whether several genes regulate the expression of the Skp2 oncogene .

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report

Research Products

(19 results)

All 2013 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (4 results) Remarks (4 results)

  • [Journal Article] Successful treatment of small cell variant anaplastic large cell lymphoma with allogeneic peripheral blood stem cell transplantation, and review of the literature2013

    • Author(s)
      Imamura R, Mouri F, Oku E, Okamura T
    • Journal Title

      Int J Hematol.

      Volume: 97 Pages: 139-143

    • DOI

      10.1007/s12185-012-1242-3

    • NAID

      10031144646

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Similar outcomesin Asian and Western patients with diffuse large B-cell lymphoma treated with R-CHOP.2013

    • Author(s)
      Castillo JJ, Sinclair N, Beltran BE et al.
    • Journal Title

      Leuk Res.

      Volume: 37(4) Pages: 386-391

    • DOI

      10.1016/j.leukres.2013.01.002

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pigment epithelium-derived factor (PEDF)inhibits survival and proliferation ofVEGF-exposed multiple myeloma cellsthrough its anti-oxidative properties.2013

    • Author(s)
      Seki R, Yamagishi S, Matsui T,et al
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 431(4) Pages: 693-697

    • DOI

      10.1016/j.bbrc.2013.01.057

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Hans algorithmis not prognostic in patients withdiffuse large B-cell lymphoma treated名)Prognostic significance of S-phase kinase-associated protein 2 and kip127in patients with diffuse large B-cell lymphoma: effects of rituximab.2012

    • Author(s)
      Castillo JJ, Beltran BE, Song MK et al
    • Journal Title

      Leuk Res.

      Volume: 21 Pages: 413-417

    • DOI

      10.1016/j.leukres.2011.12.012

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unrelated cord blood transplantation for patients with adult T-cell leukemia/lymphoma: experience at a single institute2012

    • Author(s)
      Nakamura T, Oku E, Mizuno S, Okamura T
    • Journal Title

      Int J Hematol.

      Volume: 96 Pages: 657-63

    • DOI

      10.1007/s12185-012-1177-8

    • NAID

      10031126764

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelets with a W127X mutation in GPIX express sufficient residual amounts of GPIbα to support adhesion to von Willebrand factor and collagen2012

    • Author(s)
      Yuka Takata et al
    • Journal Title

      Int J Hematol.

      Volume: 96(6) Pages: 733-742

    • DOI

      10.1007/s12185-012-1216-5

    • NAID

      10031144612

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelets with a W127X mutationcombination with CHOP chemotherapy for the treatment of diffuse large B-cell lymphoma in Japan: A retrospective analysis of 1,057 cases from Kyushu Lymphoma Study Group.2010

    • Author(s)
      Yuka Takata,Taisuke Kanaji,MasaakiMoroi, Ritsuko Seki, et a
    • Journal Title

      Int J Hematol.

      Volume: 91 Pages: 258-266

    • DOI

      10.1007/s12185-009-0475-2

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] びまん性大細胞型B細胞性リンパ腫におけるSkp2/p27kip蛋白の予後因子としての有用性2010

    • Author(s)
      関律子、大島孝一、岡村孝.
    • Journal Title

      臨床血液

      Volume: 51 Pages: 1741-1743

    • NAID

      130004501367

    • URL

      https://www.jstage.jst.go.jp/FF01S040Initsourceurl=%2Farticle%2Frinketsu%2F51%2F12%2F51_12_1741%2F_pdf

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of S-phase kinase-associated protein 2 and p27kip1in patients with diffuse large B-cell lymphoma: effects of rituximab.2010

    • Author(s)
      Ritsuko Seki, Koichi Ohshima, Tomoaki Fujisaki, et al.
    • Journal Title

      Annals of Oncology

      Volume: 21 Pages: 833-841

    • DOI

      10.1093/annonc/mdp481

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of S-phase kinase-associated protein 2 and p27^<kip1> in patients with diffuse large B-cell lymphoma : effects of rituximab.2010

    • Author(s)
      Ritsuko Seki
    • Journal Title

      Annals of Oncology

      Volume: 21 Pages: 833-841

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B-cell lymphoma in Japan : A retrospective analysis of 1,057 cases from Kyushu Lymphoma Study Group.2010

    • Author(s)
      Ritsuko Seki
    • Journal Title

      Int J Hematol.

      Volume: 91 Pages: 258-266

    • NAID

      10026111459

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] DNA Microarray Analysis in DLBCL Dependent on Skp2 Expression Ritsuko Seki,Fumiko Arakawa, Kaori Yasuda, Atushi Doi2011

    • Author(s)
      Toshihiro Miyamoto, Koichi Akashi, Koichi Ohshima
    • Organizer
      Takashi Okamura 53nd American Society of Hematology (ASH)
    • Place of Presentation
      San Diego Convention Center, USA
    • Year and Date
      2011-12-10
    • Related Report
      2012 Final Research Report
  • [Presentation] DLBCLにおけるSkp2発現に関するcDNAマイクロアレイ解析2011

    • Author(s)
      関律子、荒川文子
    • Organizer
      長藤宏司ら第51回日本リンパ網内系学会総会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2011-06-30
    • Related Report
      2012 Final Research Report
  • [Presentation] DLBCLにおけるSkip2発現に関するcDNAマイクロアレイ解析2011

    • Author(s)
      関 律子
    • Organizer
      第51回日本リンパ網内系学会総会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] DNA Microarray Analysis in DLBCL Dependent on Skp2 Expression2011

    • Author(s)
      Ritsuko Seki
    • Organizer
      53nd American Society of Hematology (ASH)
    • Place of Presentation
      San Diego Convention Center U.S.A
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.kurume-u-blood.net/

    • Related Report
      2012 Final Research Report
  • [Remarks] 久留米大学医学部 内科学講座 血液・腫瘍内科部門

    • URL

      http://www.kurume-u-blood.net/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 久留米大学医学部 内科学講座 血液・腫瘍内科部門

    • URL

      http://www.kurume-u-blood.net/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.kurume-u-blood.net/

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-22   Modified: 2019-07-29  

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