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Fundamental research on the development of treatment for triple negative breast cancer

Research Project

Project/Area Number 20591561
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKawasaki Medical School

Principal Investigator

KUREBAYASHI Junichi  Kawasaki Medical School, 医学部, 准教授 (10248255)

Co-Investigator(Kenkyū-buntansha) MORIYA Takuya  川崎医科大学, 医学部, 教授 (00230160)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords乳癌 / トリプルネガティブサブタイプ / Src / エトポシド / 癌幹細胞 / トリプルネガティブ / ダサチニブ / BRCA1
Research Abstract

Expression levels of estrogen receptor, progesterone receptor and HER2 in breast cancer tissues have been routinely measured in clinics to predict responses to endocrine therapy and anti-HER2 therapy. Breast tumors expressing none of these three receptors are named as triple negative breast cancer (TNBC). TNBC responds to neither endocrine therapy nor anti-HER2 therapy, is biologically aggressive, tends to recur earlier, and renders a poor prognosis. These findings prompt us to develop new treatment strategies against TNBC. First, we investigated a protein expression profile of various genes related to TNBC characteristics in a panel of human breast cancer cell lines. Next, we studied antitumor activity, effects on cell cycle progression, apoptosis and cancer stem cell population induced by DNA-damaging cytotoxic agents and molecular targeting agents in the panel of breast cancer cell lines. These experimental results have revealed that a Src signal inhibitor, dasatinib and a DNA-damaging agent, etoposide show potent antitumor effect on breast cancer cells of basal B subtype associated with G1-S blockade and induction of apoptosis for dasatinib or G2/M retardation and induction of apoptosis for etoposide, respectively. It is indicated for the first time that dasatinib reduces a proportion of putative cancer stem cells. We also investigated clinical significance of activation of Src signaling using immunohistochemistry in patients with breast cancer. The results of this study have indicated that activation of Src signaling may increase metastatic potential of breast cancer cells.

Report

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

    (55 results)

All 2011 2010 2009 2008

All Journal Article (35 results) (of which Peer Reviewed: 26 results) Presentation (14 results) Book (6 results)

  • [Journal Article] The cell cycle profile (C2P) test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy.2011

    • Author(s)
      Kurebayashi J, Moriya T, et al.
    • Journal Title

      Jpn J Clin Oncol. 27(Epub ahead of print)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological significance of Y416Src and Y527Src expression in breast cancer.2011

    • Author(s)
      Kanomata N, Kurebayashi J, et al.
    • Journal Title

      J Clin Pathol. 13(Epub ahead of print)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The cell cycle profile (C2P) test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy.2011

    • Author(s)
      Kurebayashi J, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype.2010

    • Author(s)
      Kurebayashi J, Moriya T, et al.
    • Journal Title

      BMC Cancer 10

      Pages: 568-568

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Management of ErbB2-positive breast cancer-insights from preclinical and clinical studies with lapatinib.2010

    • Author(s)
      Vogel C, Kurebayashi J, et al.
    • Journal Title

      Jpn J Clin Oncol 40

      Pages: 999-1013

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌培養細胞を用いた前臨床研究2010

    • Author(s)
      紅林淳一
    • Journal Title

      最新医学 65

      Pages: 1400-1410

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular-morphological approach to the pathological study of development and advancement of human breast cancer.2010

    • Author(s)
      Moriya T, Kurebayashi J, et al.
    • Journal Title

      Medical Molecular Morphology 43

      Pages: 67-73

    • NAID

      10026443320

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preclinical rationale for combined treatments of endocrine therapy with 5-fluorouracil but with neither doxorubicin nor paclitaxel in the treatment of endocrine responsive breast cancer.2010

    • Author(s)
      Kurebayashi J, et al.
    • Journal Title

      Cancer Chemother Pharmacol 65

      Pages: 219-225

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society.2010

    • Author(s)
      Iwase H, Kurebayashi J, et al.
    • Journal Title

      Breast Cancer 17(2)

      Pages: 118-24

    • NAID

      10027255494

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype.2010

    • Author(s)
      Kurebayashi J, et al.
    • Journal Title

      BMC Cancer

      Volume: 10 Pages: 568-568

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Management of ErbB2-positive breast cancer-insights from preclinical and clinical studies with lapatinib.2010

    • Author(s)
      Vogel C, Kurebayashi J, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 40 Pages: 999-1013

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌培養細胞を用いた前臨床研究2010

    • Author(s)
      紅林淳一
    • Journal Title

      最新医学

      Volume: 65 Pages: 1400-1410

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Preclinical rationale for combined treatments of endocrine therapy with 5-fluorouracil but with neither doxorubicin nor paclitaxel in the treatment of endocrine responsive breast cancer2010

    • Author(s)
      紅林淳一, et al.
    • Journal Title

      Cancer Chemother Pharmacol 65

      Pages: 219-225

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The cell cycle profile(C2P)test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy2010

    • Author(s)
      紅林淳一, et al.
    • Journal Title

      Eur J Cancer 8

      Pages: 100-100

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular-morphological approach to the pathological study of development and advancement of human breast cancer2010

    • Author(s)
      Moriya T, et al.
    • Journal Title

      Medical Molecular Morphology (In press)

    • NAID

      10026443320

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society2010

    • Author(s)
      Iwase H, et al.
    • Journal Title

      Breast Cancer (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for anthracycline-based chemotherapy for human breast cancer2010

    • Author(s)
      Miyoshi Y, et al.
    • Journal Title

      Breast Cancer (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌培養細胞を用いた前臨床研究2010

    • Author(s)
      紅林淳一
    • Journal Title

      最新医学 65(In press)

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Possible Treatment strategies for triple-negative breast cancer on the basis of molecular characteristics.2009

    • Author(s)
      Kurebayashi J
    • Journal Title

      Breast Cancer 16

      Pages: 275-280

    • NAID

      10027254794

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible Treatment strategies for triple-negative breast cancer on the basis of molecular characteristics2009

    • Author(s)
      紅林淳一
    • Journal Title

      Breast Cancer 16

      Pages: 275-280

    • NAID

      10027254794

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「乳癌と臨床検査」腫瘍マーカー2009

    • Author(s)
      紅林淳一
    • Journal Title

      Medical Technology 37

      Pages: 446-461

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      紅林淳一
    • Journal Title

      みんなに役立つ乳癌の基礎と臨床(医薬ジャーナル社)

      Pages: 167-173

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      紅林淳一
    • Journal Title

      これからの乳癌診療2009-2010(金原出版社)

      Pages: 54-61

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      紅林淳一
    • Journal Title

      乳がん標準化学療法の実際(第2版)(金原出版社)

      Pages: 138-144

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      紅林淳一
    • Journal Title

      乳癌テーラーメード治療の理論と実践(金原出版社)

      Pages: 93-100

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Possible Treatment Strategies for Triple-Negative Breast Cancer on the Basis of Molecular Characteristics.2009

    • Author(s)
      Kurebayashi J
    • Journal Title

      Breast Cancer 16(In Press)

    • NAID

      10027254794

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive correlation of the expression levels of monocyte chemotactic protein-1 in tumor cells with lymph node involvement and recurrence in patients with papillary thyroid carcinomas.2009

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

      Thyroid 19

      Pages: 21-25

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistance to paclitaxel therapy is related with Bc1-2 expression through an estrogen receptor mediated pathway in breast cancer.2009

    • Author(s)
      Tabuchi Y, et al.
    • Journal Title

      Int J Oncol 34

      Pages: 313-319

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxel in human breast cancers.2008

    • Author(s)
      Miyoshi Y, Kurebayashi J, et al.
    • Journal Title

      J Cancer Res Clin Oncol 134

      Pages: 561-567

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Topoisomerase IIalpha-positive and BRCA1-negative phenotype : Association with favorable response to epirubicin-based regimens for human breast cancers.2008

    • Author(s)
      Miyoshi Y, Kurebayashi J, et al.
    • Journal Title

      Cancer Lett 264

      Pages: 44-53

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子発現プロファイルによる日本人乳癌の特徴2008

    • Author(s)
      紅林淳一
    • Journal Title

      臨床外科 63

      Pages: 1055-1059

    • Related Report
      2010 Final Research Report
  • [Journal Article] Capecitabine and paclitaxel combination chemotherapy for inoperable or recurrent breast cancer : a phase I dose-finding study by the Kinki Breast Cancer Study Group.2008

    • Author(s)
      Masuda N, et al.
    • Journal Title

      Cancer Chemother Pharmacol 61

      Pages: 989-995

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low nuclear grade but not cell proliferation predictive of pathological complete response to docetaxgl in human breast cancers.2008

    • Author(s)
      Miyoshi Y, et al.
    • Journal Title

      J Cancer Res Clin Oncol 134

      Pages: 561-567

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topoisomerase IIalpha-positive and BRCA1-negative phenotype: Association with favorable response to epirubicin-based regimens for human breast cancers.2008

    • Author(s)
      Miyoshi Y, et al.
    • Journal Title

      Cancer Lett 264

      Pages: 44-53

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子発現プロファイルによる日本人乳癌の特徴.2008

    • Author(s)
      紅林淳一
    • Journal Title

      臨床外科 63

      Pages: 1055-1059

    • Related Report
      2008 Annual Research Report
  • [Presentation] 術後補助化学療法を受けた乳癌患者におけるC2P検査の予後予測因子としての有用性2010

    • Author(s)
      紅林淳一, 他
    • Organizer
      第48回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 術後補助化学療法を受けた乳癌患者におけるC2P検査の予後予測因子としての有用性2010

    • Author(s)
      紅林淳一, 他
    • Organizer
      第48回日本癌治療学会学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2010-10-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Triple negative乳癌を対象とした分子標的薬2010

    • Author(s)
      紅林淳一
    • Organizer
      第18回乳癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2010-06-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Triple negative乳癌を対象とした分子標的薬2010

    • Author(s)
      紅林淳一
    • Organizer
      第18回乳癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2010-06-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] The cell cycle profile (C2P) test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy.2010

    • Author(s)
      Kurebayashi J, et al.
    • Organizer
      The 7th European Breast Cancer Conference
    • Place of Presentation
      バルセロナ
    • Year and Date
      2010-03-24
    • Related Report
      2010 Final Research Report
  • [Presentation] The cell cycle profile(C2P)test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy2010

    • Author(s)
      紅林淳一, et al.
    • Organizer
      The 7th European Breast Cancer Conference
    • Place of Presentation
      バルセロナ
    • Year and Date
      2010-03-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌:臨床の立場から2009

    • Author(s)
      紅林淳一
    • Organizer
      第14回日本外科病理学会学術集会
    • Place of Presentation
      福島
    • Year and Date
      2009-10-09
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 乳癌サブタイプ別の治療法の選択2009

    • Author(s)
      紅林淳一
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] 乳癌サプタイプ別の治療法の選択2009

    • Author(s)
      紅林淳一
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳癌のエストロゲン感受性・抵抗性の分子機構2009

    • Author(s)
      紅林淳一
    • Organizer
      第41回日本臨床分子形態学会・学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2009-09-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] 甲状腺未分化癌に対する分子標的薬を用いた新しい治療戦略2009

    • Author(s)
      紅林淳一, 他
    • Organizer
      第21回日本内分泌外科学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-05-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌に対する新規薬物療法の開発2009

    • Author(s)
      紅林淳一
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2009-04-02
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌の薬物療法に関する基礎的検討2008

    • Author(s)
      紅林淳一, 他
    • Organizer
      第16回日本乳癌学会学術総会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2008-09-26
    • Related Report
      2010 Final Research Report
  • [Presentation] トリプルネガティブ乳癌の薬物療法に関する基礎的検討.2008

    • Author(s)
      紅林淳一, 他
    • Organizer
      第16回日本乳癌学会学術総会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2008-09-26
    • Related Report
      2008 Annual Research Report
  • [Book] 非浸潤性乳管癌(ductal carcinoma in situ : DCIS)のすべて2010

    • Author(s)
      紅林淳一(分担執筆)
    • Total Pages
      7
    • Publisher
      篠原出版新社
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Book] みんなに役立つ乳癌の基礎と臨床2009

    • Author(s)
      紅林淳一(分担執筆)
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Final Research Report
  • [Book] 乳癌テーラーメード治療の理論と実践2009

    • Author(s)
      紅林淳一(分担執筆)
    • Publisher
      金原出版社
    • Related Report
      2010 Final Research Report
  • [Book] これからの乳癌診療2009-20102009

    • Author(s)
      紅林淳一
    • Publisher
      金原出版社(In Press)
    • Related Report
      2008 Annual Research Report
  • [Book] みんなに役立つ乳癌の基礎と臨床2009

    • Author(s)
      紅林淳一
    • Publisher
      医薬ジャーナル社(In Press)
    • Related Report
      2008 Annual Research Report
  • [Book] 乳がん標準化学療法の実際(第2版)2009

    • Author(s)
      紅林淳一
    • Publisher
      金原出版社(In Press)
    • Related Report
      2008 Annual Research Report

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

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