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2004 Fiscal Year Final Research Report Summary

Correlation of microsatellite instability (MSI) and sensitivity for anti-cancer drugs in endometrial cancer

Research Project

Project/Area Number 15591778
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SUSUMU Nobuyuki  Keio University, Department of Medicine, Assistant Professor, 医学部, 専任講師 (90206459)

Co-Investigator(Kenkyū-buntansha) AOKI Daisuke  Keio University, Department of Medicine, Assistant Professor, 医学部, 専任講師 (30167788)
BANNO Kouji  Keio University, Department of Medicine, Instructor, 医学部, 助手 (70265875)
Project Period (FY) 2003 – 2004
Keywordsendometrial cancer / Microsatellite instability(MSJ) / DNA Mismatch Repair(MMR) gene / hMLH1 / methylation / immunohistochemistry / drug sensitivity test / Histoculture Drug Response Assay(HDRA)
Research Abstract

In advanced endometrial cancers, adjuvant chemotherapy is often needed for preventing from recurrence, however, no evidence has been established about which adjuvant therapy is better, chemotherapy or radiotherapy. We, therefore, examined whether microsatellite instability(MSI) is useful maker or not for individualized treatment for patients with endometrial cancers.
1 MSI : (1)We analyzed MSI state of clinically obtained specimens of endometrial cancers and several cell lines derived from endometrial cancers by methylation-specific PCR in several MSI markers, and found that 35% cases of endometrial cancers showed MSI and this rate was higher than that of colorectal cancers. (2)In immunohistochemical studies using antibodies against DNA mismatch repair(MMR) proteins of hMLH1, hMSH2, hMSH6, MSI cases showed the reduction of either MMR protein in significantly high rate. However, non-sense mutation of hMLH1 was found only 1 case (6% of MSI cases) and methylation of hMLH1 promoter region w … More as recognized in a significantly higher rate than in microsatellite stability (MSS) cases. Therefore, we considered that the cause of high MSI rate in endometrial cancers is derived from methylation of hMLH1 promoter region.
2 Anti-cancer drugs sensitivity test by Histoculture Drug Response Assay(HDRA)
By calculating the IC_<50> value in use of MMT assay for cytotoxic effects of cisplatin against tumor tissues obtained from endometrial cancer tissues, we divides those cases into two categories, high-sensitivity group and low-sensitivity group. In 15 MSI cases, 14 cases(93%) were judged as less sensitive. This rate was significantly higher than that of MSS cases. In addition, we confirmed that the low-sensitivities of endometrial cancer cell lines for cisplatin were recovered by adding unmethylation procedures by using Collagen gel droplet enbedded drug sensitivity test (CDDST).
Thus, we demonstrated the fact that MSI cases is less sensitive for the first time. Furthermore, we showed that the methylation state of hMLH1 promoter region is an important information in choosing the adjuvant therapy(chemotherapy or radiation therapy). Less

  • Research Products

    (51 results)

All 2005 2004 2003 2000

All Journal Article (48 results) Book (3 results)

  • [Journal Article] Diagnostic clinical application of two-color fluorescence in situ hybridization that detects chromosome 1 and 17 alterations to direct touch smear and liquid-based thin-layer cytologic preparations of endometrial cancers2005

    • Author(s)
      N.Susumu
    • Journal Title

      International Journal of Gynecological Cancer 15(1)

      Pages: 70-80

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical characteristics of prognostic factors in poorly-differentiated (G3) endometrioid adenocarcinoma in Japan2005

    • Author(s)
      Y.Kuwabara
    • Journal Title

      Japanese Journal of Clinical Oncology 35(1)

      Pages: 23-27

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability-positive endometrial cancer2005

    • Author(s)
      T.Iwata
    • Journal Title

      Clinical Cancer Research 11(10)

      Pages: 3949-3957

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sensitivity to cisplatin determined by the histoculture drug response assay and clinical response of endometrial cancer2005

    • Author(s)
      M.Kanasugi
    • Journal Title

      International Journal of Gynecological Cancer (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid and ascites from patients with advanced ovarian cancer : Case Reports2005

    • Author(s)
      M.Kawaguchi
    • Journal Title

      Anticancer Research (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 臨床検査,診断に用いる腫瘍マーカー 婦人科腫瘍2005

    • Author(s)
      青木大輔
    • Journal Title

      癌と化学療法 32(3)

      Pages: 411-416

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Efficient screening for ovarian cancers using a combination of tumor markers CA602 and CA5462005

    • Author(s)
      M.Saito
    • Journal Title

      International Journal of Gynecological Cancer 15(1)

      Pages: 37-44

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ドセタキセルの有用性 体癌への応用をふまえて2005

    • Author(s)
      進 伸幸
    • Journal Title

      特定非営利活動法人婦人科悪性腫瘍化学療法研究機構 化療ニュース 13(4)

      Pages: 4-5

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemosensitivity testing of ovarian cancer using the histoculture drug response assay : sensitivity to cisplatin and clinical response2005

    • Author(s)
      S.Nakada
    • Journal Title

      International Journal of Gynecological Cancer 15(3)

      Pages: 445-452

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical characteristics of prognostic factors in poorly-differentiated (G3) endometrioid adenocarcinoma in Japan2005

    • Author(s)
      Y.Kuwabara, N.Susumu, K.Banno, T.Hirao, M.Kawaguchi, W.Yamagami, N.Suzuki, D.Aoki, S.Nozawa
    • Journal Title

      Japanese Journal of Clinical Oncology 35(1)

      Pages: 23-27

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Diagnostic clinical application of two-color fluorescence in situ hybridization that detectschromosome 1 and 17 alterations to direct touch smear and liquid-based thin-layer cytologic preparations of endometrialcancers2005

    • Author(s)
      N.Susumu, D.Aoki, T.Noda, Y.Nagashima, K.Banno, A.Suzuki, N.Suzuki, H.Tsuda, J.Inazawa, S.Nozawa
    • Journal Title

      International Journal of Gynecological Cancer 15(1)

      Pages: 70-80

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Efficient screening for ovarian cancers using a combination of tumor markers CA602 and CA5462005

    • Author(s)
      M.Saito, D.Aoki, N.Susumu, A.Suzuki, N.Suzuki, Y.Udagawa, S.Nozawa
    • Journal Title

      International Journal of Gynecological Cancer 15(1)

      Pages: 37-44

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chemosensitivity testing of ovarian cancer using the histoculture drug response assay : sensitivity to cisplatin and clinical response2005

    • Author(s)
      S.Nakada, D.Aoki, S.Ohie, M.Horiuchi, N.Suzuki, M.Kanasugi, N.Susumu, Y.Udagawa, S.Nozawa
    • Journal Title

      International Journal of Gynecological Cancer 15(3)

      Pages: 445-452

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability-positive endometrial cancer2005

    • Author(s)
      T.Iwata, T.Fujita, N.Hirao, Y.Matsuzaki, T.Okada, H.Mochimaru, N.Susumu, B.Matsumoto, K.Sugano, N.Yamashita, S.Nozawa, Y.Kawakami
    • Journal Title

      Clinical cancer research 11(10)

      Pages: 3949-3957

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid and ascites from patients with advanced ovarian cancer : Case Reports2005

    • Author(s)
      M.Kawaguchi, K.Banno, N.Susumu, M.Yanokura, Y.Kuwabara, N.Hirao, K.Tsukazaki, S.Nozawa
    • Journal Title

      Anticancer Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sensitivity to cisplatin determined by the histoculture drug response assay and clinical response of endometrial cancer2005

    • Author(s)
      M.Kanasugi, D.Aoki, N.Suzuki, N.Susumu, S.Nakata, M.Horiuchi, Y.Udagawa, S.Nozawa
    • Journal Title

      International Journal of Gynecological Cancer (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel retinoid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), induces apoptosis of human ovarian carcinoma cells and shows potential as a new antitumor agent for clear cell adenocarcinoma2004

    • Author(s)
      N.Suzuki
    • Journal Title

      Gynecol Oncol 94(3)

      Pages: 643-649

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Met668 Ile and Leu390Phe of the MSH2 gene are not functional mutations, but polymorphisms in Japanese individuals2004

    • Author(s)
      K.Banno
    • Journal Title

      Cancer Genetics and Cytogenetics 155(1)

      Pages: 92-92

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC), Amsterdam Criteria II2004

    • Author(s)
      K.Banno
    • Journal Title

      Journal of Obstetrics and Gynaecology Research 30(4)

      Pages: 287-292

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of HNPCC and endometrial cancers2004

    • Author(s)
      K.Banno
    • Journal Title

      International Journal of Clinical Oncology 9(4)

      Pages: 262-269

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] HMMC-1 :a humanized monoclonal antibody with therapeutic potential against Mullerian duct-ralated carcinomas2004

    • Author(s)
      S.Nozawa
    • Journal Title

      Clinical Cancer Research 10(20)

      Pages: 7071-7078

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer cells to human mesothelial cells2004

    • Author(s)
      N.Suzuki
    • Journal Title

      Gynecol Oncol 95(2)

      Pages: 290-298

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] III.子宮体癌 子宮体癌の治療 卵巣癌の診断 腫瘍マーカー2004

    • Author(s)
      青木大輔
    • Journal Title

      日本臨床 62(Suppl.10)

      Pages: 496-502

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 疾患別臨床検査パーフェクトガイド-EBMとDRG/PPSを念頭に-2004

    • Author(s)
      青木大輔
    • Journal Title

      診断と治療 92(Suppl.)

      Pages: 487-495

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] III.子宮体癌 子宮体癌の治療 保存的療法としてのホルモン療法2004

    • Author(s)
      進 伸幸
    • Journal Title

      日本臨床 62(Suppl.10)

      Pages: 375-380

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] III.子宮体癌 子宮体癌の治療 治療概論2004

    • Author(s)
      青木大輔
    • Journal Title

      日本臨床 62(Suppl.10)

      Pages: 324-328

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel retinoid, 4-[3,5-bis(trimethylsilyl) benzamido] benzoic acid (TAC-101), induces apoptosis of human ovarian carcinoma cells and shows potential as a new antitumor agent for clear cell adenocarcinoma2004

    • Author(s)
      N.Suzuki, D.Aoki, S.Oie, M.Horiuchi, Y Hasegawa, S.Ezawa, A.Suzuki, N.Susumu, F.Hosoi, K.Kitazato, S.Nozawa
    • Journal Title

      Gynecol Oncol 94(3)

      Pages: 643-649

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Met668 Ile and Leu390Phe of the MSH2 gene are not functional mutations, but polymorphisms in Japanese individuals2004

    • Author(s)
      K.Banno, N.Susumu, S.Nozawa, K.Sugano
    • Journal Title

      Cancer Genetics and Cytogenetics 155(1)

      Pages: 92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC), Amsterdam Criteria II2004

    • Author(s)
      K.Banno, N.Susumu, T.Hirao, M.Yanokura, A.Hirasawa, D.Aoki, Y.Udagawa, K.Sugano, S.Nozawa
    • Journal Title

      Journal of Obstetrics and Gynaecology Research 30(4)

      Pages: 287-292

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of HNPCC and endometrial cancers2004

    • Author(s)
      K.Banno, N.Susumu, M.Yanokura, T.Hirao, T.Iwata, A.Hirasawa, D.Aoki, K.Sugano, S.Nozawa
    • Journal Title

      International Journal of Clinical Oncology 9(4)

      Pages: 262-269

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer cells to human mesothelial cells2004

    • Author(s)
      N.Suzuki, D.Aoki, Y.Tamada, N.Susumu, K.Orikawa, K.Tsukazaki, M.Sakayori, A.Suzuki, T.Fukuchi, M.Mukai, K.Kojima-Aikawa, I.Ishida, S.Nozawa
    • Journal Title

      Gynecol Oncol. 95(2)

      Pages: 290-298

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] p16^<INK4a> Overexpression and human papillomavirus infection in small cell carcionoma of the uterine cervix2003

    • Author(s)
      N.Masumoto
    • Journal Title

      Human Pathology 34(8)

      Pages: 778-783

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Subcellular localization of galactosyltransferase associated with tumors in endometrial and ovarian cancer cells2003

    • Author(s)
      N.Susumu
    • Journal Title

      Acta Histochemica et Cytochemica 36(3)

      Pages: 205-214

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of germline MSH_2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer2003

    • Author(s)
      K.Banno
    • Journal Title

      Cancer Genetics and Cytogenetics 146(1)

      Pages: 58-65

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets2003

    • Author(s)
      A.Hirasawa
    • Journal Title

      Clinical Cancer Research 9

      Pages: 1995-2004

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Galactosyltransferase associated with tumor in patients with ovarian cancer : Factors involved in elevation of serum galactosyltranserase2003

    • Author(s)
      E.Saito
    • Journal Title

      International Journal of Oncology 23(2)

      Pages: 303-310

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer2003

    • Author(s)
      A.Hirasawa
    • Journal Title

      Clinical Cancer Research 9(15)

      Pages: 5675-2682

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 遺伝性非腺腫症性大腸癌(HNPCC)と子宮内膜癌2003

    • Author(s)
      阪埜浩司
    • Journal Title

      家族性腫瘍 3(2)

      Pages: 62-67

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 遺伝性子宮内膜癌とは-特にDNAミスマッチ修復遺伝子について2003

    • Author(s)
      阪埜浩司
    • Journal Title

      産婦人科の世界 55(8)

      Pages: 3-10

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Muller管関連腫瘍に対するヒトモノクローナル抗体の作製と認識抗原の検討2003

    • Author(s)
      青木大輔
    • Journal Title

      日本分子腫瘍マーカー研究会誌 19

      Pages: 51-52

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 妊娠・出産にかかわる婦人科疾患 婦人科悪性疾患2003

    • Author(s)
      青木大輔
    • Journal Title

      ペリネイタルケア 22(11)

      Pages: 13-20

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] p16^<INK4a> Overexpression and human papillomavirus infection in small cell carcionoma of the uterine cervix2003

    • Author(s)
      N.Masumoto, T.Fujii, M.Ishikawa, M.Saito, T.Iwata, T.Fukuchi, N.Susumu, M.Mukai, K.Kubshiro, K.Tsukazaki, S.Nozawa
    • Journal Title

      Human Pathology 34(8)

      Pages: 778-783

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Subcellular localization of galactosyltransferase associated with tumors in endometrial and ovarian cancer cells2003

    • Author(s)
      N.Susumu, H.Kawakami, D.Aoki, N.Suzuki, A.Suzuki, T.Uejima, H.Hirano, S.Nozawa
    • Journal Title

      Acta Histochemica et Cytochemica 36(3)

      Pages: 205-214

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of germline MSH_2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer2003

    • Author(s)
      K.Banno, N.Susumu, T.Hirao, M.Yanokura, A.Hirasawa, D.Aoki, Y.Udagawa, K.Sugano, S.Nozawa
    • Journal Title

      Cancer Genetics and Cytogenetics 146(1)

      Pages: 58-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets2003

    • Author(s)
      A.Hirasawa, F.Saito-Ohara, J.Inoue, D.Aoki, N.Susumu, T.Yokoyama, S.Nozawa, J.Inazawa, I.Imoto
    • Journal Title

      Clinical Cancer Research 9

      Pages: 1995-2004

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Galactosyltransferase associated with tumor in patients with ovarian cancer : Factors involved in elevation of serum galactosyltranserase2003

    • Author(s)
      B.Saito, D.Aoki, N.Susumu, Y.Udagawa, S.Nozawa
    • Journal Title

      International Journal of Oncology 23(2)

      Pages: 303-310

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer2003

    • Author(s)
      A.Hirasawa, D.Aoki, J.Inoue, I.Imoto, N.Susumu, K.Sugano, S.Nozawa, J.Inazawa
    • Journal Title

      Clinical Cancer Research 9(15)

      Pages: 5675-5682

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] HMMC-1 : a humanized monoclonal antibody with therapeutic potential against Mullerian duct-ralated carcinomas2000

    • Author(s)
      S.Nozawa, D.Aoki, K.Tsukazaki, N.Susumu, M.Sakayori, N.Suzuki, A.Suzuki, R.Wakita, M.Mukai, Y Egami, K.Kojima-Aikawa, I.Ishida, F.Belot, O.Hindsgaul, M.Fukuda, M.N.Fukuda
    • Journal Title

      Clinical Cancer Research 10(20)

      Pages: 7071-7078

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] クリエイティブサイトロジー2 子宮内膜細胞診の臨床的価値とその限界-精度向上をめざして-2005

    • Author(s)
      照井仁美
    • Total Pages
      76
    • Publisher
      武藤化学株式会社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 標準産科婦人科学第3版(婦人科編-女性性器の疾患)2004

    • Author(s)
      野澤志朗(丸尾猛, 岡井崇編)
    • Total Pages
      600
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 住民検診・職域検診・人間ドックのためのがん検診計画ハンドブック2004

    • Author(s)
      鈴木直(三木一正, 渡邊能行編)
    • Total Pages
      189
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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