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Characterization of tumors from the viewpoint of tumor stem cells

Research Project

Project/Area Number 20590364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionOsaka University

Principal Investigator

MORII Eiichi  Osaka University, 大学院・医学系研究科, 准教授 (10283772)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords腫瘍幹細胞 / 病理診断 / 予後解析 / 腫瘍 / マーカー / 病理学
Research Abstract

Tumor is composed of a single clone, but the character of individual tumor cells is different one another. Tumor stem cells are resistant to various anti-tumor therapies, and are responsible for recurrence. The evaluation of the amount of tumor stem cells at diagnosis would be helpful for suitable plan of anti-cancer therapy. However, to date, no such evaluation system was established. Here, we evaluated the amount of tumor stem cells by immunohistochemistry, and revealed that cases with rich tumor stem cells showed poor prognosis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (70 results)

All 2011 2010 2009 2008 Other

All Journal Article (48 results) (of which Peer Reviewed: 47 results) Presentation (20 results) Book (2 results)

  • [Journal Article] Frequency of intravascular large B-cell lymphoma in Japan : study of the Osaka Lymphoma Study Group.2011

    • Author(s)
      千原剛、森井英一(他11名、12番目)
    • Journal Title

      J Hematol Oncol 4

      Pages: 14-14

    • Related Report
      2010 Final Research Report
  • [Journal Article] Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications.2011

    • Author(s)
      ラハディアン=ヌル、森井英一(他10名、12番目)
    • Journal Title

      Cancer Sci 102

      Pages: 903-908

    • NAID

      10029292931

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epstein-Barr virus in diffuse large B-cell lymphoma in immunocompetent patients in Japan is as low as in Western countries.2011

    • Author(s)
      和田直樹、森井英一(他11名、12番目)
    • Journal Title

      J Med Virol 83

      Pages: 317-321

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epstein-Barr virus in diffuse large B-cell lymphoma in immunocompetent patients in Japan is as low as in Western contries.2011

    • Author(s)
      Wada N, et al
    • Journal Title

      J Med Virol

      Volume: 83 Pages: 317-321

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic potential of mononucleated small cells of Hodgkin lymphoma cell lines.2010

    • Author(s)
      池田純一郎、森井英一(他6名、8番目)
    • Journal Title

      Am J Pathol 177

      Pages: 3081-3088

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diffuse large B-cell lymphoma in the spinal epidural space : A study of the Osaka Lymphoma Study Group.2010

    • Author(s)
      和田直樹、森井英一(他12名、13番目)
    • Journal Title

      Pathol Res Pract 206

      Pages: 439-444

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of CUB domain containing protein expression in endometrioid adenocarcinoma.2010

    • Author(s)
      ママト=スハナ、森井英一(他9名、11番目)
    • Journal Title

      Oncol Rep 23

      Pages: 1221-1227

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma.2010

    • Author(s)
      ラハディアン=ヌル、森井英一(他8名、10番目)
    • Journal Title

      Ann Surg Oncol 17

      Pages: 1311-1323

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma.2010

    • Author(s)
      池田純一郎、森井英一(他5名、7番目)
    • Journal Title

      Pathol Res Pract 206

      Pages: 376-378

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic potential of mononucleated small cells of Hodgkin lymphoma cell lines.2010

    • Author(s)
      Ikeda J, et al
    • Journal Title

      Am J Pathol

      Volume: 177 Pages: 1235-1245

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic role of podoplanin in esophageal squamous cell carcinoma.2010

    • Author(s)
      Rahadiani N, et al
    • Journal Title

      Annals Surg Oncol

      Volume: 17 Pages: 1311-1323

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression level of PBX2 correlates with poor prognosis of gastric adenocarcinoma and esophageal carcinoma2010

    • Author(s)
      Qiu Y, et al
    • Journal Title

      Int J Oncol

      Volume: 36 Pages: 651-663

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polymophous lymphoproliferatice disorder : a clinicopathological analysis2010

    • Author(s)
      Nakamichi N, et al
    • Journal Title

      Virchows Arch

      Volume: 456 Pages: 269-276

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties2010

    • Author(s)
      Nagahama Y, et al
    • Journal Title

      Cancer Res

      Volume: 70 Pages: 1215-1224

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peropheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma2010

    • Author(s)
      Ikeda J, et al
    • Journal Title

      Pathol Res Pract

      Volume: 206 Pages: 376-378

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral T-cell lymphoma of Lennert type complicated by monoclonal proliferation of large B-cells2010

    • Author(s)
      Chihara T, et al
    • Journal Title

      Pathol Res Pract

      Volume: 206 Pages: 185-190

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphoproliferative disease of the kidney developing in fibro-inflammatory lesion2010

    • Author(s)
      Hori Y, et al
    • Journal Title

      Pathol Re Pract

      Volume: 206 Pages: 134-137

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression level of PBX2 correlates with poor prognsis of gastric adenocarcinoma and esophageal carcinoma2010

    • Author(s)
      Qiu Y, et al
    • Journal Title

      Int J Oncol 36

      Pages: 651-663

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polymophous lymphoproliferatice disorder : a clinicopathological analysis2010

    • Author(s)
      Nakamichi N, et al
    • Journal Title

      Virchows Arch 456

      Pages: 269-276

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties2010

    • Author(s)
      Nagahama Y, et al
    • Journal Title

      Cancer Res 70

      Pages: 1215-1224

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral T-cell lymphoma of Lennert type complicated by monoclonal proliferation of large B-cells2010

    • Author(s)
      Chihara T, et al
    • Journal Title

      Pathol Res Pract 206

      Pages: 185-190

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphoproliferative disease of the kidney developing in fibro-inflammatory lesion2010

    • Author(s)
      Hori Y, et al
    • Journal Title

      Pathol Re Pract 206

      Pages: 134-137

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased type 3 iodothyronine deiodinase activity in a regrown hepatic hemangioma with consumptive hypothyroidism2010

    • Author(s)
      Bessho K, et al
    • Journal Title

      Eur J Pediatr 169

      Pages: 215-221

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diffuse large B-cell lymphoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lymphoma) : a study of Osaka Lymphoma Study Group.2009

    • Author(s)
      和田直樹、森井英一(他9名、11番目)
    • Journal Title

      Virchows Arch 455

      Pages: 285-93

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic role of orphan nuclear receptor NROB1 in lung adenocarcinoma.2009

    • Author(s)
      小田知文、森井英一(他6名,8番目)
    • Journal Title

      Am J Pathol 175

      Pages: 1235-45

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma2009

    • Author(s)
      Oda T, et al
    • Journal Title

      Am J Pathol 175

      Pages: 1235-1245

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caspase-1, caspase-8, and calparin are dispensable for IL-33 release by macrophages2009

    • Author(s)
      Ohno T, et al
    • Journal Title

      J Immunol 183

      Pages: 7890-7897

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diffuse large B-cell lympgoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lymphoma) : a study of Osaka Lymphoma Study Group2009

    • Author(s)
      Wada N, et al
    • Journal Title

      Virchows Arch 455

      Pages: 285-293

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of PBX2 expression in non-small cell lung carcinoma2009

    • Author(s)
      Qiu Y, et al
    • Journal Title

      Cancer Sci 100

      Pages: 1198-1209

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of disseminated peritoneal leiomyomatosis developing after laparoscope-assisted myomectomy2009

    • Author(s)
      Miyake T, et al
    • Journal Title

      Gynecol Obstet Invest 67

      Pages: 96-102

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Change of CD20 expression in diffuse large B-cell lymphoma treated with rituximab, an anti-CD20 monoclonal antibody : a study of the Osaka Lymphoma Study Group2009

    • Author(s)
      Wada N, et al
    • Journal Title

      Case Rep Oncol 2

      Pages: 194-202

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of heat shock protein 105 in lung adenocarcmoma.2009

    • Author(s)
      Oda T, Morii E, et al
    • Journal Title

      Mol Med Reports (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of interleukin-6 and endoplasmic reticulumstress inducers on the high level of ABCG2 expression in plasma cells.2009

    • Author(s)
      Nakamichi N, Morii E, et al
    • Journal Title

      Lab Invest (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of CUB domain containing protein (CDCP1)is correlated with prognosis and survival of patients with adenocarcinoma of lung.2009

    • Author(s)
      Ikeda JI, Morii E, et al
    • Journal Title

      Cancer Sci (In press)

    • NAID

      10025143186

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of CD55 expression in breast cancer.2008

    • Author(s)
      Ikeda J, Morii E, et al
    • Journal Title

      Clin Cancer Res 14

      Pages: 4780-4786

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LMP-1 of EB virus induces the expression of B-cell integration cluster, a precursor form of miR-155 in B lymphoma cells.2008

    • Author(s)
      Rahadiani N, Morii E, et al
    • Journal Title

      Biochem Biophys Res Comm 377

      Pages: 579-583

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NK-cell intravascular lymphomatosis-a mini-review2008

    • Author(s)
      Nakamichi, Morii E, et al
    • Journal Title

      Eur J Haematol 81

      Pages: 1-7

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of elongator protein 3 (ELP3) expression in endometrioid adenocarcinoma.

    • Author(s)
      ワン=イ、森井英一(他8名、10番目)
    • Journal Title

      Oncol Let in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of aldehyde dehydrogenase 1 expression in stromal cells of diffuse large B-cell lymphoma.

    • Author(s)
      藤田茂樹、森井英一(他5名、2番目)
    • Journal Title

      Exp Therap Med in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.

    • Author(s)
      小根山千歳、森井英一(他8名、7番目)
    • Journal Title

      Oncogene in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Presence of B-cell clones in T-cell lymphoma.

    • Author(s)
      ザキ=モナ、森井英一(他10名、11番目)
    • Journal Title

      Eur J Haematol in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications.

    • Author(s)
      Rahadiani N, et al
    • Journal Title

      Cancer Sci

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.

    • Author(s)
      Oneyama C, et al
    • Journal Title

      Oncogene

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumorigenic role of podoplanin in esophageal squamous cell carcinoma

    • Author(s)
      Rahadiani N, et al
    • Journal Title

      Annals Surg Oncol (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of CUB domain containing protein expression in endometrioid adenocarcinoma

    • Author(s)
      Mamat S, et al
    • Journal Title

      Oncol Rep (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peropheral T-cell lymphoma developing at ileocolonic anastomosis site after colectomy for adenocarcinoma

    • Author(s)
      Ikeda J, et al
    • Journal Title

      Pathol Res Pract (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Squamous cell carcinoma of the uterine cervix producing granulocyte colony-stimulating factor : a report of 4 cases and a review of the literature

    • Author(s)
      Matsumoto Y, et al
    • Journal Title

      Int J Gynecol Cacner (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The first two cases of granulocyte colony stimulating factor producing adenocarcinoma of the uterine cervix

    • Author(s)
      Mabuchi S, et al
    • Journal Title

      Int J Gynecol Pathol (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Srcによるがん形質発現のmicroRNAによる調節機構2010

    • Author(s)
      小根山千歳、池田純一郎、鈴木慶、狩野孝、奥崎大介、森井英一、青笹克之, 岡田雅人
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 腫瘍幹細胞の観点からみた腫瘍研究2010

    • Author(s)
      森井英一
    • Organizer
      第51回日本組織細胞化学会
    • Place of Presentation
      秋葉原コンベンションホール
    • Year and Date
      2010-09-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 炎症の腫瘍動態への影響-炎症細胞豊富なリンパ腫の腫瘍原性を求めて-2010

    • Author(s)
      森井英一、池田純一郎、青笹克之
    • Organizer
      日本病理学会第7回病理学カンファレンス
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2010-08-07
    • Related Report
      2010 Final Research Report
  • [Presentation] 炎症の腫瘍動態への影響について2010

    • Author(s)
      森井英一
    • Organizer
      日本病理学会カンファレンス
    • Place of Presentation
      岡山コンベンションセンター(招待講演)
    • Year and Date
      2010-08-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] A role of small-sized cell population in tumourigenesis of Hodgkin lymphoma.2010

    • Author(s)
      池田純一郎、森井英一、青笹克之
    • Organizer
      英国病理学会
    • Place of Presentation
      St. Andrews University
    • Year and Date
      2010-06-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 肺腺癌の腫瘍幹細胞:核内レセプター発現の関与2010

    • Author(s)
      森井英一
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2010-04-29
    • Related Report
      2010 Final Research Report
  • [Presentation] ホジキンリンパ腫の腫瘍形成能における小型細胞群の役割2010

    • Author(s)
      池田純一郎、森井英一、青笹克之
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2010-04-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 肺腺癌における腫瘍幹細胞の観点からみた核内レセプター蛋白質に関する解析2010

    • Author(s)
      森井英一
    • Organizer
      日本病理学会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2010-04-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] マーキング技術を利用した腫瘍幹細胞の同定2009

    • Author(s)
      森井英一
    • Organizer
      日本病理学会第9回病理技術講習会
    • Place of Presentation
      グランドヒル市ヶ谷
    • Year and Date
      2009-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] A role of small-sized cell population in tumorigenesis of Hodgkin lymphomaホジキンリンパ腫の造腫瘍能における小型細胞集団の役割2009

    • Author(s)
      池田純一郎、森井英一、青笹克之
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma肺腺癌における核内レセプターNR0B1の役割2009

    • Author(s)
      森井英一、池田純一郎、青笹克之
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma2009

    • Author(s)
      森井英一
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肺癌細胞株のside population分画に高発現する核内レセプター蛋白質に関する解析2009

    • Author(s)
      森井英一、池田純一郎、青笹克之
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-05-02
    • Related Report
      2010 Final Research Report
  • [Presentation] 肺腺癌におけるCDCP1の発現と臨床病理学的特徴2009

    • Author(s)
      池田純一郎、森井英一、奥村明之進、青笹克之
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-05-02
    • Related Report
      2010 Final Research Report
  • [Presentation] 肺腺癌細胞株の side population 分画に高発現する核内レセプター蛋白質に関する解析2009

    • Author(s)
      森井英一
    • Organizer
      日本病理学会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2009-05-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肺腺癌における新規レセプターCDCP1の発現意義2008

    • Author(s)
      森井 英一, 池田純一郎, 青笹克之
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] B細胞性リンパ腫の腫瘍発生とNotch2発現との関連2008

    • Author(s)
      池田純一郎, 森井英一, 青笹克之
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍幹細胞について2008

    • Author(s)
      森井 英一
    • Organizer
      第42回日本病理学会近畿支部学術総会
    • Place of Presentation
      兵庫医科大学
    • Year and Date
      2008-09-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍幹細胞マーカーについて2008

    • Author(s)
      森井 英一
    • Organizer
      第5回日本病理学会カンファレンス
    • Place of Presentation
      湘南国際センター
    • Year and Date
      2008-08-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腫瘍幹細胞的な性格を有するCD55高発現細胞の解析2008

    • Author(s)
      森井 英一, 池田 純一郎, 青笹 克之
    • Organizer
      第97回日本病理学会学術総会
    • Place of Presentation
      ホテル日航金沢
    • Year and Date
      2008-05-16
    • Related Report
      2008 Annual Research Report
  • [Book] 癌診療のための病理診断プラクティス リンパ球増殖疾患2010

    • Author(s)
      森井英一
    • Total Pages
      333
    • Publisher
      中山書店
    • Related Report
      2010 Annual Research Report
  • [Book] 解明病理学2009

    • Author(s)
      森井英一
    • Total Pages
      827
    • Publisher
      医歯薬出版
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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