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Investigation aimed for establishment of novel bladder cancer detection and treatment strategy system using centrosome amplification

Research Project

Project/Area Number 19390416
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionYamaguchi University

Principal Investigator

MATSUYAMA Hideyasu  Yamaguchi University, 大学院・医学系研究科, 教授 (70209667)

Co-Investigator(Kenkyū-buntansha) NAGAO Kazuhiro  山口大学, 大学院・医学系研究科, 助教 (70379949)
OKUDA Masaru  山口大学, 農学部, 准教授 (10325243)
SASAKI Kousuke  山口大学, 大学院・医学系研究科, 助教 (80116722)
内藤 克輔  山口大学, 大学院・医学系研究科, 教授 (60115251)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords中心体複製異常 / 膀胱癌 / ゲノム変異 / 染色体不安定性
Research Abstract

Objectives:
The aims of this study are (1) to testify the role of centrosome amplification (CA) using bladder washing cytology specimen for the prediction of tumor recurrence and progression in non muscle-invasive bladder cancer, (2) to explore the specific genomic alterations (deletion, amplification) regarding CA, and (3) to identify the relation of CA to anticancer drug sensitivity to taxanes by comparing the status of CA with drug sensitivity using six established bladder cancer cell lines.
Materials & Methods:
(1) An immune-fluorescent staining for anti-pericentrin was applied to bladder washing cytology specimens as well as corresponding touch biopsy specimens obtained both from 85 human non muscle-invasive bladder cancers. CA was defined as cases with having more than 5% fraction of cells with three or more centrosome per cell. (2) An array-CGH (comparative genomic hybridization) using 4030 AC crone chip (MacArray) was applied to tumor genomic DNAs extracted from 70 human urothelia … More l cancers, and compared the copy number of entire chromosomes between DNA from cases with CA and those without CA. (3) Paclitaxel (final conc. : 0.1, 1, 10nM/ml) was continuously exposed to six human established bladder cancer cell lines (CA cell line : T24, EJ-1, 5637, J-82, TCC-sup, non-CA cell line : KK47, RT-4) in vitro, and compared CA status with drug sensitivity to paclitaxel.
Results:
(1) Out of 85 cases examined, CA and tumor progression was observed in 50 (59%) and 15 (18%) cases, respectively. A multivariate analysis by Cox-proportional hazard model revealed CA was a sole independent prognostic factor predicting for tumor progression (p=0.0098, Relative risk : 3.69, 95% CI : 1.28-13.44). CA detection using bladder washing specimens was successful in 20 out of 25 cased (80%), and correspondence rate between cytology and touch specimens was 95%. (2) High throughput genomic analysis demonstrated that cases with CA were significantly higher accumulated variant copy number, higher chromosome instability (CIN), and shorter period to tumor progression than those without CA. Specific chromosomal region with copy number aberrations included gains for 5p15.2,20p12.2, and losses for 2q37.3, 8p22, and 17p12, respectively. (3) All cell lines without CA demonstrated dose-response drug sensitivity to paclitaxel, while three of four cell lines with CA showed resistant to the drug.
Conclusions:
A serial experiments regarding CA demonstrated that (1) CA detection using bladder washing cytology specimens may become a non-invasive diagnostic tool for predicting tumor progression, (2) urothelial cancer including bladder may be biologically categorized by CA status, (3) CA status may predict clinical efficacy of anti-cancer chemotherapy using paclitaxel. Less

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (26 results)

All 2009 2008 2007 2006

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (12 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Molecular cloning of the canine fragile histidine triad (FHIT) gene and Fhit protein expression in canine peripheral blood mononuclear cells.2009

    • Author(s)
      Hiraoka, H., Minami, K., Kaneko, N., Miyama, T., Mizuno, T., Okuda, M
    • Journal Title

      J Vet Med Sci. 71

      Pages: 645-9

    • NAID

      130000134378

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrations of the FHIT gene and the Fhit protein in canine lymphoma cell.2009

    • Author(s)
      Hiraoka, H., Minami, K., Kaneko, N., Miyama, T., Mizuno, T., Okuda, M.
    • Journal Title

      J Vet Med Sci. 71

      Pages: 769-77

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular Centrosome Number is correlated with Copy Number of Chromosome in Bladder Cancer.2009

    • Author(s)
      Yamamoto, Y., Eguchi, S., Akao, J., Furuya, T., Oga, A., Kawauchi, S., Sasaki, K., Matsuyama, H.
    • Journal Title

      Cancer Genet. Cytogenet 191

      Pages: 38-42

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytogenetic analysis of false-positive mucosa by photodynamic diagnosis using 5-aminolevulinic acid-possible existence of premalignant genomic alterations examined by in vitro experiment.2009

    • Author(s)
      Matsuyama, H., Yamamoto, Y., Nagao, K., Ohmi, C., Sakano, S., Sasaki K.
    • Journal Title

      Oncology 76

      Pages: 118-25

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 9p21 index as estimated by dual-color fluorescence in situ hybridization is useful to predict urothelial carcinoma recurrence in bladder washing cytology.2009

    • Author(s)
      Kawauchi, S, Sakai, H, Ikemoto, K, Eguchi, S, Nakao, M, Takihara, H, Shimabukuro, T, Furuya, T, Oga, A, Matsuyama, H, Takahashi, M, Sasaki, K
    • Journal Title

      Hum Pathol 40

      Pages: 1783-9

    • NAID

      120001613389

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellualr Centrosome Number is correlated with Copy Number of Chromosome in Bladder Cancer.2009

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

      Cancer Genetics & cytogenetics 191

      Pages: 38-42

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytogenetic analysis of false-positive mucosa by photodynamic diagnosis using 5-aminolevulinic acid-possible existence of premalignant genomic alterations examined by in vitro experiment.2009

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

      Oncology 76

      Pages: 118-125

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 9p21 index as estimated by dual-color fluorecence in situ hybridization is useful to predict urothelial carcinoma recurrence in bladder washing cytology2009

    • Author(s)
      Kawauchi, S., et al :
    • Journal Title

      Human Pathology 40

      Pages: 1783-1789

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of the canine fragile histidine triad (FHIT)gene and Fhit protein expression in canine peripheral blood mononuclear cells2009

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

      Jornal of Veterinary Medical Science 71

      Pages: 645-649

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrations of the FHIT gene and the Fhit protein in canine lymphoma cell lines2009

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

      Jornal of Veterinary Medical Science 71

      Pages: 769-770

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of the canine fragile histidine triad (FHIT) gene and Fhit prote in expression in canine peripheral blood mononuclear cells.2009

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

      Jornal of Veterinary Medical Science 71 (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrations of the FHIT gene and the Fhit protein in canine lymphoma cell lines2009

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

      Jornal of Veterinary Medical Science 71 (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular Centrosome Number is correlated with Copy Number of chromosome in Bladder Cancer.2009

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

      Cancer Genetics and Cytogenetics (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膀胱癌における中心体複製異常の検討2009

    • Author(s)
      宮近義浩、松山豪泰、山本義明、坂野滋、原貴彦、長尾一公、伊藤英昭、三角拓、西嶋淳
    • Organizer
      第47回日本癌治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-09-14
    • Related Report
      2009 Final Research Report
  • [Presentation] 膀胱癌における中心体複製異常検討2009

    • Author(s)
      宮近義浩
    • Organizer
      第47回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜、神奈川
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical significance of false positive mucosa by photodynamic diagnosis-possible existence of premalignant genomic alterations-.2009

    • Author(s)
      Matsuyama, H., Yamamoto, Y., Nagao, K., Sakano, S., Sasaki, K
    • Organizer
      AUA (American Urological Association) 2009 Annual meeting
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2009-04-27
    • Related Report
      2009 Final Research Report
  • [Presentation] Clinical significance of false positive mucosa by photodynamic diagnosis-possible existence of premalignant genomic alterations-2009

    • Author(s)
      Matsuyama, H., et al :
    • Organizer
      American Urological Association 2009 Annual meeting
    • Place of Presentation
      Chicago, McCormic Place, USA
    • Year and Date
      2009-04-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膀胱癌における中心体複製異常の臨床的検討-膀胱洗浄液検体を用いた検討-2009

    • Author(s)
      宮近義浩、松山豪泰、山本義明、内藤克輔、坂野滋、原貴彦、井上亮、江口賢、伊藤英昭、赤尾淳平、三角拓
    • Organizer
      第97回日本泌尿器科学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-04-18
    • Related Report
      2009 Final Research Report
  • [Presentation] 膀胱癌における中心体複製異常の臨床的検討-膀胱洗浄検体を用いた検討-2009

    • Author(s)
      宮近義浩
    • Organizer
      第97回日本泌尿器科学会総会
    • Place of Presentation
      岡山コンベンションセンター、岡山
    • Year and Date
      2009-04-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical significance of centrosome amplification as prognostic marker for tumor progression in non-muscle invasive bladder cancer.2009

    • Author(s)
      Matsuyama, H., Yamamoto, Y. Miyachika, Y
    • Organizer
      The 24th Annual EAU (European Association of Urology) Congress
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2009-03-19
    • Related Report
      2009 Final Research Report
  • [Presentation] Clinical significance of centrosome amplification as prognostic marker for tumor progression in non-muscle invasive bladder cancer.2009

    • Author(s)
      Matsuyama, H., et al.
    • Organizer
      The 24^<th> Annual EAU (European Association of Urology) Congress
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2009-03-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] 膀胱癌における中心体複製異常の臨床的応用-膀胱洗浄液検体を用いた検討-.2008

    • Author(s)
      松山豪泰、山本義明、江口賢、長尾一公、大見千英高、坂野滋、佐々木功典、内藤克輔
    • Organizer
      第96回日本泌尿器科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-27
    • Related Report
      2009 Final Research Report
  • [Presentation] Could all non-malignant fluorescenct mucosa be interpreted as insignificant false-positive observation? Molecular analysis on bladder mucosa with and without red fluorescence detected by fluorescence cystoscopy using 5-aminolevulinic acid.2008

    • Author(s)
      Matsuyama, H., Nagao, K., Ohmi, C., Sakano, S., Naito, K.
    • Organizer
      The 23rd Annual EAU (European Association of Urology) Congress
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-03-27
    • Related Report
      2009 Final Research Report
  • [Presentation] Clinical significance of centrosome amplification and its associated numerical aberrations in non-muscle invasive bladder cancer.2007

    • Author(s)
      Matsuyama, H., Yamamoto, Y., Akao, J., Misumi, T., Kawai, Y., Eguchi, S., Nagao, K., Ohmi, C., Sakano, S., Sasaki, K., Naito, K.
    • Organizer
      102nd annual meeting of the American Urological Association
    • Place of Presentation
      Anaheim, USA
    • Year and Date
      2007-05-21
    • Related Report
      2009 Final Research Report
  • [Presentation] Clinical significance of centrosome amplification and its associated numerical aberrations in non- muscle invasive bladder cancer.2007

    • Author(s)
      Matsuyama, H.
    • Organizer
      102nd annual meeting of the American Urological Association
    • Place of Presentation
      USA,Anaheim
    • Year and Date
      2007-05-21
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 中心体複製異常を指標とした膀胱癌の予後診断2006

    • Inventor(s)
      松山豪泰、内藤克輔、佐々木功典、奥田優
    • Industrial Property Rights Holder
      山口大学
    • Patent Publication Number
      2006-275989
    • Filing Date
      2006-03-30
    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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