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DNA damage detected with γH2AX induced by anticancer drugs on ovarian clear cell carcinoma

Research Project

Project/Area Number 22591864
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionIwate Medical University

Principal Investigator

SUGIYAMA Toru  岩手医科大学, 医学部, 教授 (40162903)

Co-Investigator(Kenkyū-buntansha) KUROSE Akira  弘前大学, 医学研究科, 教授 (70244910)
KUMAGAI Seisuke  岩手医科大学, 医学部, 講師 (20289474)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords癌 / 病理学 / 酵素 / 核酸 / DNA傷害 / 化学療法 / アポトーシス / γH2AX / フローサイトメトリー / 細胞周期 / 子宮癌 / 卵巣癌
Research Abstract

Differences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) of the ovary, endometrioid adenocar cinoma of the uterine corpus, and squamous cell carcinoma of the cervix were determined using phosphory- lation of histon H2AX (γH2AX).1. Clear cell adenocarcinoma of the ovary (CCC): After administration of cisplatin(CDDP), DNA damage was frequent in S -phase cells, while cell-cycle arrest occurred in the G1 and G2/M phases and γH2AX did not increase in CDDP-resistant cells. Sensitivities to CDDP and carboplatin(CBDCA) differed between the two cell lines. The antitumor effect of paclitaxel(PTX) is induced by G2/M arrest, and combination treatment with CBDCA, inducing DNA damage in G2/M-phase cells, might be effective.This is the first study in Japan to evaluate the antitumor activity of anticancer agents by focusing on the relationship between the cell cycle and DNA damage using γH2AX as an indicator. The immunocytochemical method used in … More this study detects γH2AX, which indicates DNA damage even at very low concentrations and with high sensitivity. Therefore, a promising method of easily and rapidly identifying agents potentially effective against CCC. 2.Endometrioid adenocarcinoma of the uterine corpus: The study revealed significant differences among the cell lines in the effects of DNA damage vis-a-vis cell cycle phasespecificity, induction of apoptosis or senescence following drug treatment. doxorubicin (DOX) treatment showed little cell cycle specificity in terms of induction of γH2AX, and its mechanism, which is similar to another anthracycline DNA topoisomerase II inhibitor mitoxantrone, may involve oxidative DNA damage modulated by other factors. Treatment with CDDP and 5-fluorouracil (5-FU) led to phosphorylation of H2AXpreferentially in S -phase cells, consistent with the induction of replication stress. The response of Ishikawa cells expressing wt p53 was different compared to other cell lines. The data suggest that the treatment of endometrioid adenocarcinoma with these drugs may have to be customized to individual patients. Less

Report

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

    (32 results)

All 2013 2012 2011 2010 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results) Presentation (9 results) Book (2 results)

  • [Journal Article] Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents.2013

    • Author(s)
      Eriko Takatori, Tadahiro Shoji, Seisuke Kumagai, Takashi Sawai, Akira Kurose, Toru Sugiyama
    • Journal Title

      Journal of Ovarian Research

      Volume: 5(1) Pages: 16-16

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neoadjuvant chemotherapy using platinum- and taxane-based regimens for bulky stage Ib2 to IIb non-squamous cell carcinoma of the uterine cervix.2013

    • Author(s)
      Tadahiro Shoji, Eriko Takatori, Tatsunori Saito, Hideo Omi, Masahiro Kagabu, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama.
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 71(3) Pages: 657-662

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pilot study of oxaliplatin with oral S-1 as second-line chemotherapy for patients with recurrent adenocarcimona of the uterine cervix.2013

    • Author(s)
      Eriko Takatori, Tadahiro Shoji, Yasuko Suga, Hanae Niinuma, Yuki Miura, Yoshitaka Kaido, Anna Takada, Masahiro Kagabu, Satoshi Takeuchi, Toru Sugiyama
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 未定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neoadjuvant chemotherapy using platinum- and taxane-based regimens for bulky stage Ib2 to IIb non-squamous cell carcinoma of the uterine cervix.2012

    • Author(s)
      Tadahiro Shoji, Eriko Takatori, Tatsunori Saito, Hideo Omi, Masahiro Kagabu, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama
    • Journal Title

      Cancer Chemotherapy and Pharmacology

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Second -Line Chemotherapy for Platinum- and Taxane-Resistant Epithelial Ovarian Cancer: Pegylated Liposomal Doxorubicin (PLD)2012

    • Author(s)
      Toru Sugiyama.
    • Journal Title

      Irinotecan, and Combination Therapies at Lower Doses

    • Related Report
      2012 Final Research Report
  • [Journal Article] Are platinum agents, paclitaxel and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX induced by anticancer agents2012

    • Author(s)
      Eriko Takatori, Tadahiro Shoji, Seisuke Kumagai, Takashi Sawai, Akira Kurose, Toru Sugiyama
    • Journal Title

      Journal of Ovarian Research

      Volume: 5(1) Pages: 16-16

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit2012

    • Author(s)
      Tadahiro Shoji, Seisuke Kumagai , Akira Yoshizaki, Yoshihito Yokoyama, Toshiro Fujimoto, Tadao Takano, Npbuo Yaegashi, Kenji Nakahara, Hiroshi Nishiyama, Toru Sugiyama
    • Journal Title

      European journal of gynaecological oncology

      Volume: 33(4) Pages: 353-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Case of peptide-YY-producing strumal carcinoid of the ovary: A case report and review.2012

    • Author(s)
      Eriko Takatori, Tadahiro Shoji, Jiyu Miura, Satoshi Takeuchi, Akira Yoshizaki, Toru Sugiyama
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 38(10) Pages: 1266-1270

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit.2012

    • Author(s)
      Tadahiro Shoji, Seisuke Kumagai, Akira Yoshizaki, Yoshihito Yokoyama, Toshiro Fujimoto, Tadao Takano, Npbuo Yaegashi, Kenji Nakahara, Hiroshi Nishiyama, Toru Sugiyama.
    • Journal Title

      European journal of gynaecological oncology

      Volume: 33(4) Pages: 353-357

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065)2012

    • Author(s)
      Satoshi Yamaguchi, Ryuichiro Nishimura, Nobuo Yaegashi, Kazushige Kiguchi, Toru Sugiyama,
    • Journal Title

      Oncology Report

      Volume: 28 (2) Pages: 487-493

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture.2012

    • Author(s)
      Sohei Yamamoto, Hitoshi Tsuda, Hideyuki Shimazaki, Masashi Takano, Tomoyuki Yoshikawa, Kazuo Kuzuya, Hiroshi Tsuda, Hirohisa Kurachi, Junzo Kigawa, Yoshihiro Kikuchi, Toru Sugiyama,
    • Journal Title

      International Journal of Gynecological Pathology

      Volume: 31(2) Pages: 116-124

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clear cell carcinoma of the ovary: is there a role of histology-specific treatment?2012

    • Author(s)
      Masashi Takano, Hiroshi Tsuda, Toru Sugiyama
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 31(53) Pages: 1-7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tako-Tsubo cardiomyopathy caused immediately following cesarean section delivery of triplets: a case report.2012

    • Author(s)
      Tadahiro Shoji, Eriko Takatori, Rie Oyama, Seisuke Kumagai, Akimune Fukushima, Akira Yoshizaki, Toru Sugiyama
    • Journal Title

      Gynecologic and Obstetric Investigation

      Volume: 74(1) Pages: 84-88

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β-PNA: peptide nucleic acid (PNA) with a chiral center at the β-position of the PNA backbone.2011

    • Author(s)
      Toru Sugiyama, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Masashi Takano, Atsushi Kittaka .
    • Journal Title

      Bioorganic & medicinal chemistry letters

      Volume: 21(24) Pages: 7317-20

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle -dependent regulation of tumor cells.2011

    • Author(s)
      Masahiko Shibazaki, Chihaya Maesawa, Kiyomi Akasaka, Shuya Kasai, Shinji Yasuhira, Kiminori Kanno, Ikue Nakayama, Toru Sugiyama, Go Wakabayasi, Tomoyuki Masuda, Nozomu Mori.
    • Journal Title

      International Journal of Oncology;

      Volume: 40(3) Pages: 695-702

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 卵巣がんに対する個別化治療の試みと実際2011

    • Author(s)
      庄子忠宏, 高取恵里子, 杉山徹
    • Journal Title

      臨床腫瘍プラクティス(ヴァン・メディカル)

      Volume: 7 Pages: 42-29

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 卵巣癌(上皮性悪性腫瘍)2011

    • Author(s)
      杉山徹
    • Journal Title

      外来癌化学療法

      Volume: 2 Pages: 92-97

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA損傷修復マーカーを用いた卵巣明細胞腺癌に対する抗癌剤の細胞効果の検討2010

    • Author(s)
      高取恵里子、黒瀬顕、庄子忠宏、杉山徹
    • Journal Title

      岩手医学会誌

      Volume: 62(1) Pages: 47-58

    • NAID

      110007609541

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA damage detected with gammaH2 AX in endometrioid adenocarcinoma cell lines2010

    • Author(s)
      Maki Ikeda, Akira Kurose , Eriko Takatori, Toru Sugiyama, Frank Traganos, Zbigniew Darzynkiewicz, Takashi Sawai.
    • Journal Title

      International Journal of Oncology

      Volume: 36(5) Pages: 1081-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA damage detected with γH2AX in endometrioid adenocarcinoma cell lines2010

    • Author(s)
      Ikeda, M
    • Journal Title

      Int J Oncol

      Volume: 36 Pages: 1081-1088

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA損傷マーカーを用いた卵巣明細胞癌に対する抗癌剤の細胞効果の検討2010

    • Author(s)
      高取恵理子
    • Journal Title

      岩手医誌

      Volume: 62 Pages: 47-58

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 局所進行子宮頸がんに対する術前化学療法(NAC)の位置付け2012

    • Author(s)
      高取恵里子、永沢崇幸、小見英夫、利部正裕、本田達也、諸原雄一、庄子忠宏、三浦史晴、竹内聡、吉崎陽、杉山徹、佐藤顕.
    • Organizer
      第64回日本産婦人科学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2012-04-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Are platinum agents, paclitaxel, and irinotecan effective for clear cell carcinoma of the ovary? DNA damage detected with γH2AX2011

    • Author(s)
      E. Takatori, T. Shoji, S. Kumagai, S. Takeuchi, T. Sugiyama
    • Organizer
      The 17th international meeting of the European Society of Gynecologycal Oncology
    • Place of Presentation
      イタリア、ミラノ
    • Year and Date
      2011-09-30
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA損傷マーカー γH2AX を用いた卵巣明細胞腺癌における抗癌剤の抗腫瘍効果解析.2011

    • Author(s)
      高取恵里子, 庄子忠宏, 熊谷晴介, 竹内聡, 杉山徹
    • Organizer
      第63回日本産婦人科学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2011-09-30
    • Related Report
      2012 Final Research Report
  • [Presentation] サイトメトリー的細胞動態解析と臨床病理への応用2011

    • Author(s)
      黒瀬 顕
    • Organizer
      第28回北日本病理研究会
    • Place of Presentation
      弘前市
    • Year and Date
      2011-06-10
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] 細胞核DNA傷害を可視化・定量化する.シンポジウム3「細胞診におけるクロマチンの意義」2011

    • Author(s)
      黒瀬 顕
    • Organizer
      第52回日本臨床細胞学会総会
    • Place of Presentation
      福岡市
    • Year and Date
      2011-05-21
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] 新カルチノイド症候群を呈した卵巣甲状腫瘍性カルチノイドの一例2010

    • Author(s)
      高取恵理子
    • Organizer
      第58回日本産科婦人科学会 北日本連合地方部会学術集会
    • Place of Presentation
      石川県金沢市金沢文化ホール
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腹腔鏡で診断したwunderlich症候群の一例2010

    • Author(s)
      高取恵理子
    • Organizer
      第129回日本産科婦人科学会 東北日本連合地方部会学術集会
    • Place of Presentation
      岩手県盛岡市メトロポリタン盛岡
    • Year and Date
      2010-05-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 局所進行子宮頚がんに対する術前化学療法(NAC)の位置付け

    • Author(s)
      髙取恵里子
    • Organizer
      日本産科婦人科学会 第64回学術講演会
    • Place of Presentation
      兵庫県神戸市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gemcitabin+Calboplatin療法が著効しIDSを行い得た進行卵巣癌の一例

    • Author(s)
      池田真妃
    • Organizer
      第50回日本癌治療学会学術集会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Annual Research Report
  • [Book] EBM婦人科疾患の治療2013-20142013

    • Author(s)
      杉山徹.苛原稔、原田省、鈴木直、川名敬.
    • Publisher
      中外医学社
    • Related Report
      2012 Final Research Report
  • [Book] 婦人科がん科学療法ハンドブック2011

    • Author(s)
      杉山徹
    • Publisher
      中外医学社
    • Related Report
      2012 Final Research Report 2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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