Analyses of DNA damage response to neoadjuvant chemotherapy in basal-like breast cancer

• Project/Area Number: 20591557
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: St.Marianna University School of Medicine
• Principal Investigator: OHTA Tomohiko St.Marianna University School of Medicine, 医学(系)研究科(研究院), 教授 (60233136)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: BRCA1 / Basal-like乳癌 / DNA損傷 / 薬剤感受性 / 術前化学療法 / 術前化学療 / Basal-like 乳癌

Research Abstract

Core needle biopsy specimens were obtained from sixty cases of primary breast cancer before and 18-24 hours after the first cycle of neoadjuvant epirubicin plus cyclophosphamide treatment. Nuclear focus formation of DNA damage repair proteins, BRCA1-, gH2AX-, or Rad51, was immunohistochemically analyzed and DNA damage response competence was evaluated as DDR score. A high DDR score significantly correlated with low tumor response to EC and EC + docetaxel whereas other clinicopathological factors analyzed did not.

Research Products

• [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, Tsuda H, Ohta T, Kurosumi M, Miyamoto K, Yamamoto Y, Iwase T
  • Journal Title: Breast Cancer. 17(2) Pages: 118-24
  • NAID: 10027255494
  • Peer Reviewed
• [Journal Article] Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins. (2010)
  • Author(s): Asakawa H, Koizumi H, Koike A, Takahashi M, Wu W, Iwase H, Fukuda M, Ohta T.
  • Journal Title: Breast Cancer Res. 12(2)
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential. (2010)
  • Author(s): Ohno Y, Yasunaga S, Ohtsubo M, Mori S, Tsumura M, Okada S, Ohta T, Ohtani K, Kobayashi M, Takihara Y
  • Journal Title: Proc Natl Acad Sci U S A. 107(50) Pages: 21529-34
  • Peer Reviewed
• [Journal Article] Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates. (2010)
  • Author(s): Koike A, Nishikawa H, Wu W, Okada Y, Venkitaraman AR, Ohta T.
  • Journal Title: Cancer Res. 70(17) Pages: 6746-56
  • Peer Reviewed
• [Journal Article] 「乳がん」、遺伝子診療学(第2版)-遺伝子診断の進歩とゲノム治療の展望- (2010)
  • Author(s): 太田智彦
  • Journal Title: 日本臨床 984巻、8号 Pages: 438-43
  • Peer Reviewed
• [Journal Article] HERC2 is an E3 ligase that targets BRCA1 for degradation. (2010)
  • Author(s): Wu W, Sato K, Koike A, Nishikawa H, Koizumi H, Venkitaraman AR, Ohta T.
  • Journal Title: Cancer Res. 70(15) Pages: 6384-92
  • Peer Reviewed
• [Journal Article] DNA損傷応答と乳癌の薬剤感受性 (2010)
  • Author(s): 太田智彦,小泉宏隆,呉文文
  • Journal Title: 乳癌の臨床2010年(篠原出版新社) 第25巻、第6号
  • Peer Reviewed
• [Journal Article] Venkitaraman AR. A mitotic role for the DNA damage-responsive CHK2 kinase. (2010)
  • Author(s): Sato K, Ohta T
  • Journal Title: Nat Cell Biol. 12(5) Pages: 424-5
  • Peer Reviewed
• [Journal Article] BRCA遺伝子異常と標的治療 (2010)
  • Author(s): 太田智彦
  • Journal Title: がん分子標的治療(メディカルレビュー社) Vol.8 No.2
  • Peer Reviewed
• [Journal Article] A mitotic role for the DNA damage-responsive CHK2 kinase. (2010)
  • Author(s): Sato K
  • Journal Title: Nature Cell Biology Volume: 12 Pages: 424-5
  • Peer Reviewed
• [Journal Article] HERC2 is an E3 ligase that targets BRCA1 for degradation. (2010)
  • Author(s): Wu W
  • Journal Title: Cancer Research Volume: 70 Pages: 6384-92
  • Peer Reviewed
• [Journal Article] Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates. (2010)
  • Author(s): Koike A
  • Journal Title: Cancer Research Volume: 70 Pages: 6746-56
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential. (2010)
  • Author(s): Ohno Y
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 Pages: 21529-34
  • Peer Reviewed
• [Journal Article] Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins. (2010)
  • Author(s): Asakawa H
  • Journal Title: Breast Cancer Research Volume: 12
  • Peer Reviewed
• [Journal Article] BRCA遺伝子異常と標的治療 (2010)
  • Author(s): 太田智彦
  • Journal Title: がん分子標的治療 Volume: 8 Pages: 46-52
  • Peer Reviewed
• [Journal Article] DNA損傷応答と乳癌の薬剤感受性 (2010)
  • Author(s): 太田智彦
  • Journal Title: 乳癌の臨床 Volume: 25 Pages: 609-15
  • Peer Reviewed
• [Journal Article] 乳がん (2010)
  • Author(s): 太田智彦
  • Journal Title: 日本臨牀 遺伝子診療学(第2版) Volume: 984 Pages: 438-43
  • Peer Reviewed
• [Journal Article] A mitotic role for the DNA damage-responsive CHK2 Kinase (2010)
  • Author(s): Ko Sato, et al
  • Journal Title: Nature Cell Biology 12(In press)
• [Journal Article] Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins. (2010)
  • Author(s): Hideki Asakawa, et al
  • Journal Title: Breast Cancer Res. 12
• [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): Hirotaka Iwase, et al
  • Journal Title: Breast Cancer 17 Pages: 118-24
  • Peer Reviewed
• [Journal Article] がんのゲノム解析と診療への応用 a)乳がん (2010)
  • Author(s): 太田智彦
  • Journal Title: 日本臨牀 (In press)
• [Journal Article] BRCA遺伝子異常と標的治療 (2010)
  • Author(s): 太田智彦
  • Journal Title: がん分子標的治療 (In press)
• [Journal Article] Contemplating chemosensitivity of basal-like breast cancer based on BRCA1 dysfunction. (2009)
  • Author(s): Ohta T, Wu W, Koike A, Asakawa H, Koizumi H, Fukuda M
  • Journal Title: Breast Cancer. 16(4) Pages: 268-74
  • NAID: 10027254733
  • Peer Reviewed
• [Journal Article] Perturbation of DNA repair pathways by proteasome inhibitors corresponds to enhanced chemosensitivity of cells to DNA damage-inducing agents. (2009)
  • Author(s): Takeshita T, Wu W, Koike A, Fukuda M, Ohta T.
  • Journal Title: Cancer Chemother. Pharmacol. 64 Pages: 1039-46
  • Peer Reviewed
• [Journal Article] BAP1 interferes with BRCA1/BARD1 RING heterodimer activity. (2009)
  • Author(s): Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M, Ohta T.
  • Journal Title: Cancer Res. 69 Pages: 111-9
  • Peer Reviewed
• [Journal Article] Radiologic-pathological correlation of punctate hyperechoic foci by ultrasound in stereotactic vacuum-assisted breast biopsy samples. (2009)
  • Author(s): Hiroko Okazaki, et al
  • Journal Title: Jpn J Radiol. 27 Pages: 438-43
  • Peer Reviewed
• [Journal Article] Contemplating chemosensitivity of basal-like breast cancer based on BRCA1 dysfunction. (2009)
  • Author(s): Tomohiko Ohta
  • Journal Title: Breast Cancer 16 Pages: 268-74
  • NAID: 10027254733
  • Peer Reviewed
• [Journal Article] Perturbation of DNA repair pathways by proteasome inhibitors crresponds to enhanced chemosensitivity of cells to DNA damage-inducing agents. (2009)
  • Author(s): Takashi Takeshita, et al
  • Journal Title: Cancer Chemother Pharmacol. 64 Pages: 1039-46
  • Peer Reviewed
• [Journal Article] Perturbation of DNA repair pathways by proteasome inhibitors corresponds to enhanced chemosensitivity of cells to DNA damage-inducing agents. (2009)
  • Author(s): Takashi Takeshita
  • Journal Title: Cancer Chemother. Pharmacol. Epub ahead of print
  • Peer Reviewed
• [Journal Article] BRCAl-associated protein l interferes with BRCAl/BARDl RING heterodimer activity. (2009)
  • Author(s): Hiroyuki Nishikawa
  • Journal Title: Cancer Res. 69(1) Pages: 111-9
  • Peer Reviewed
• [Journal Article] Contemplating chemosensitivity of basal-like breast cancer based on BRCAl dysfunction (2009)
  • Author(s): Tomohiko Ohta
  • Journal Title: Breast Cancer (In press)
  • Peer Reviewed
• [Journal Article] Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society (2009)
  • Author(s): Hirotaka Iwase
  • Journal Title: Breast Cancer (In press)
  • Peer Reviewed
• [Journal Article] The UPS : A promising target for breast cancer treatment. (2008)
  • Author(s): Sato K, Rajendra E, Ohta T.
  • Journal Title: BMC Biochem. 9(suppl 1):S2 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis. (2008)
  • Author(s): Shimo A, Tanikawa C, Nishidate T, Lin ML, Matsuda K, Park JH, Ueki T, Ohta T, Hirata K, Fukuda M, Nakamura Y, Katagiri T
  • Journal Title: Cancer Sci. 99 Pages: 62-70
  • NAID: 10024000927
  • Peer Reviewed
• [Journal Article] The ubiquitin E3 ligase activity of BRCA1 and its biological functions. (2008)
  • Author(s): Wu W, Koike A, Takeshita T, Ohta T.
  • Journal Title: Cell Div. 3:1 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Modification of the hepatic mitochondrial proteome in response to ischemic preconditioning following ischemia-reperfusion injury of the rat liver. (2008)
  • Author(s): Oshima R, Nakano H, Katayama M, Sakurai J, Wu W, Koizumi S, Asano T, Watanabe T, Asakura T, Ohta T, Otsubo T
  • Journal Title: Eur Surg Res. 40 Pages: 247-55
  • Peer Reviewed
• [Journal Article] The UPS : a promising target for breast cancer treatment. (2008)
  • Author(s): Ko Sato
  • Journal Title: BMC Biochem. 9 Suppl 1 : S2(Open access)
  • Peer Reviewed
• [Journal Article] The ubiquitin E3 ligase activity of BRCAl and its biological functions (2008)
  • Author(s): Wenwen Wu
  • Journal Title: Cell Div. Jan 7 ; 3:1.(Open access)
  • Peer Reviewed
• [Presentation] 乳がんのDNA相同組換え修復異常とユビキチン (2010)
  • Author(s): 太田智彦
  • Organizer: 第69回日本癌学会学術総会・シンポジウム
  • Place of Presentation: 大阪国際会議場(大阪)
• [Presentation] Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates. (2010)
  • Author(s): 太田智彦
  • Organizer: EMBO Workshop-The interface between the ubiquitin family and the DNA damage response.
  • Place of Presentation: Hotel Istra (Croatia)
• [Presentation] DNA損傷応答と乳癌の薬剤感受性 (2010)
  • Author(s): 太田智彦
  • Organizer: 第18回日本乳癌学会学術総会・シンポジウム
  • Place of Presentation: ロイトン札幌(北海道)
• [Presentation] The DNA damage repair pathway in breast cancer chemotherapy. (2010)
  • Author(s): 太田智彦
  • Organizer: The 23rd International Symposium of the Foundation for Promotion of Cancer Research
  • Place of Presentation: 国立がんセンター Recent Progress on Breast Cancer(東京都)
• [Presentation] The DNA damage repair pathway in breast cancer chemotherapy (2010)
  • Author(s): Tomohiko Ohta
  • Organizer: The 23rd International Symposium of the Foundation for Promotion of Cancer Research "Recent Progress on Breast
  • Place of Presentation: 東京(国立がんセンター)
• [Presentation] DNA損傷応答と乳癌の薬剤感受性 (2010)
  • Author(s): 太田智彦
  • Organizer: 第18回日本乳癌学会学術総会、シンポジウム
  • Place of Presentation: 北海道(ロイトン札幌)
• [Presentation] Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates. (2010)
  • Author(s): Tomohiko Ohta
  • Organizer: EMBO Workshop-The interface between the ubiquitin family and the DNA damage response.-
  • Place of Presentation: Croatia (Hotel Istra)
• [Presentation] 乳がんのDNA相同組換え修復異常とユビキチン (2010)
  • Author(s): 太田智彦
  • Organizer: 第69回日本癌学会学術総会、シンポジウム
  • Place of Presentation: 大阪(大阪国際会議場)
• [Presentation] 乳癌の化学療法感受性とBRCA1 (2009)
  • Author(s): 太田智彦
  • Organizer: 第19回乳癌基礎研究会
  • Place of Presentation: 伊香保温泉(群馬県)
  • Year and Date: 2009-07-25
• [Presentation] REGULATION OF NUCLEOPHOSMIN BY BRCA1 E3 UBIQUITIN LIGASE. (2009)
  • Author(s): Ayaka Koike, et al
  • Organizer: Cold Spring Harbor Laboratory Meeting-The Ubiquitin Family-
  • Place of Presentation: New York, USA
  • Year and Date: 2009-04-22
• [Presentation] The E3 ligase activity of HERC2 regulates BRCA1-mediated G2/M checkpoint function independent of BARD1. (2009)
  • Author(s): Wenwen Wu, et al
  • Organizer: Cold Spring Harbor Laboratory Meeting-The Ubiquitin Family-
  • Place of Presentation: New York, USA
  • Year and Date: 2009-04-22
• [Presentation] REGULATION OF NUCLEOPHOSMIN BY BRCA1 E3 UBIQ UITIN LIGASE (2009)
  • Author(s): Ayaka Koike, et al
  • Organizer: Cold Spring Harbor Laboratory Meeting-The Ubiquitin Family-
  • Place of Presentation: New York, USA
  • Year and Date: 2009-04-22
• [Presentation] The E3 ligase activity of HERC2 regulates BRCA1-mediated G2/M checkpoint function independent of BARD1 (2009)
  • Author(s): Wenwen Wu, et al
  • Organizer: Cold Spring Harbor Laboratory Meeting-The Ubiquitin Family-
  • Place of Presentation: New York, USA
  • Year and Date: 2009-04-22
• [Presentation] BRCA1機能不全をtargetにした乳癌の化学療法 (2009)
  • Author(s): 太田智彦
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2009-04-02
• [Presentation] BRCA1を標的とするユビキチンリガーゼの同定 (2008)
  • Author(s): 太田智彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2008-10-29
• [Presentation] BRCAlを標的とするュビキチンリガーゼの同定 (2008)
  • Author(s): 太田智彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] BRCA1の機能から考えたBasal-like乳癌の薬剤感受性 (2008)
  • Author(s): 太田智彦
  • Organizer: 第16回日本乳癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2008-09-27
• [Presentation] BRCA1の機能から考えたBasal-like乳癌の薬剤感受性 (2008)
  • Author(s): 太田智彦
  • Organizer: 第16回日本乳癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-27
• [Presentation] DNA double-strand break repair mediated by BRCA1. (2008)
  • Author(s): 太田智彦
  • Organizer: 26th Congress of the International Association for Breast Cancer Research.
  • Place of Presentation: 岡山県
  • Year and Date: 2008-09-23
• [Presentation] DNA double-strand break repair mediated by BRCAl (2008)
  • Author(s): Tomohiko Ohta
  • Organizer: 26^<th> Congress of the International Association for Breast Cancer Research
  • Place of Presentation: 岡山
  • Year and Date: 2008-09-23
• [Presentation] Candidate substrates of BRCA1 in its multiple cellular functions. (2008)
  • Author(s): 太田智彦
  • Organizer: 2nd JCA-AACR special Joint Conference : The latest Advance in Breast Cancer Research From Basic Science to Therapeutics.
  • Place of Presentation: 兵庫県
  • Year and Date: 2008-07-14
• [Presentation] Candidate substrates of BRCAl in its multiple cellular functions (2008)
  • Author(s): Tomohiko Ohta
  • Organizer: 2^<nd> JCA-AACR special Joint Conference : The latest Advance in Breast Cancer Research From Basic Science to Therapeutics
  • Place of Presentation: 兵庫
  • Year and Date: 2008-07-14
• [Presentation] BRCA1カスケードによる遺伝子恒常性維持と家族性腫瘍 (2008)
  • Author(s): 太田智彦
  • Organizer: 第14回日本家族性腫瘍学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2008-06-21
• [Presentation] BRCA1カスケードによる遺伝子恒常性維持と家族性腫瘍 (2008)
  • Author(s): 太田智彦
  • Organizer: 第1 4回日本家族性腫瘍学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-21
• [Remarks] ホームページ等
  • URL: http://www.marianna-u.ac.jp/t-oncology/index.html
• [Remarks]
  • URL: http://www.marianna-u.ac.jp/t-oncology/index.html
• [Remarks]
  • URL: http://www.marianna-u.ac.jp/t-oncology/
• [Remarks]
  • URL: http://www.marianna-u.ac.jp/gakunai/jabcs/index.html