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Elucidation of molecular targets based on epithelial-mesenchymal transition for the treatment of renal cell carcinoma

Research Project

Project/Area Number 24390374
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Urology
Research InstitutionKeio University

Principal Investigator

OYA Mototsugu  慶應義塾大学, 医学部, 教授 (00213885)

Co-Investigator(Kenkyū-buntansha) MIKAMI Shuji  慶應義塾大学, 医学部, 講師 (20338180)
KIKUCHI Eiji  慶應義塾大学, 医学部, 講師 (10286552)
NAKAGAWA Ken  東京歯科大学, 歯学部, 教授 (50227740)
MIZUNO Ryuichi  慶應義塾大学, 医学部, 講師 (60383824)
ASANUMA Hiroshi  慶應義塾大学, 医学部, 講師 (70245570)
MIYAJIMA Akira  慶應義塾大学, 医学部, 准教授 (90245572)
NAGATA Hirohiko  慶應義塾大学, 医学部, 研究員 (90265900)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords腎細胞癌 / 分子標的治療 / 薬剤耐性 / CD44 / mTOR
Outline of Final Research Achievements

Molecular targeted agents are widely used and better survival benefits are shown for the treatment of metastatic renal cell carcinoma (RCC). However, there are still hurdles to conquer RCC because survival cancer cells survive. The phenotype survival cancer cells look like sarcoma suggesting epithelial- mesenchymal transition. We found out that CD44 is up-regulated in the cells where Tumor Necrosis Factor (TNF)-α induces the expression.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (33 results)

All 2014 2013 2012

All Journal Article (21 results) (of which Peer Reviewed: 21 results,  Open Access: 1 results) Presentation (11 results) Book (1 results)

  • [Journal Article] Invasion and metastasis of renal cell carcinoma.2014

    • Author(s)
      Mikami S, Oya M, Mizuno R, Kosaka T, Katsube KI, Okada Y
    • Journal Title

      Med Mol Morphol

      Volume: 47(2) Issue: 2 Pages: 63-7

    • DOI

      10.1007/s00795-013-0064-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study.2014

    • Author(s)
      Tanaka N, Kikuchi E, Shirotake S, Kanao K, Matsumoto K, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Ito Y, Kosaka T, Kodaira K, Oyama M, Miyajima A, Momma T, Nakagawa K, Ueno M, Oya M
    • Journal Title

      Eur Urol

      Volume: 65(1) Issue: 1 Pages: 227-34

    • DOI

      10.1016/j.eururo.2012.11.050

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Independent Predictors for Bladder Outcomes after Treatment of Intravesical Recurrence following Radical Nephroureterectomy in Patients with Primary Upper Tract Urothelial Carcinoma.2014

    • Author(s)
      Tanaka N, Kikuchi E, Kanao K, Matsumoto K, Shirotake S, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Hagiwara M, Kosaka T, Oyama M, Miyajima A, Momma T, Nakagawa K, Jinzaki M, Hasegawa S, Nakajima Y, Oya M
    • Journal Title

      Ann Surg Oncol

      Volume: 21(9) Issue: 9 Pages: 3151-8

    • DOI

      10.1245/s10434-014-3657-y

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metastatic behavior of upper tract urothelial carcinoma after radical nephroureterectomy: association with primary tumor location.2014

    • Author(s)
      Tanaka N, Kikuchi E, Kanao K, Matsumoto K, Kobayashi H, Ide H, Miyazaki Y, Obata J, Hoshino K, Shirotake S, Akita H, Kosaka T, Miyajima A, Momma T, Nakagawa K, Hasegawa S, Nakajima Y, Jinzaki M, Oya M
    • Journal Title

      Ann Surg Oncol

      Volume: 21(3) Issue: 3 Pages: 1038-45

    • DOI

      10.1245/s10434-013-3349-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: a multi-institutional study.2014

    • Author(s)
      Tanaka N, Kikuchi E, Kanao K, Matsumoto K, Shirotake S, Kobayashi H, Miyazaki Y, Ide H, Obata J, Hoshino K, Hayakawa N, Kosaka T, Oyama M, Miyajima A, Momma T, Nakagawa K, Jinzaki M, Nakajima Y, Oya M
    • Journal Title

      Urol Oncol

      Volume: 32(1) Issue: 1 Pages: 48.e19-48.e26

    • DOI

      10.1016/j.urolonc.2013.07.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of TNF-α and CD44 is implicated in poor prognosis, cancer cell invasion, metastasis and resistance to the sunitinib treatment in clear cell renal cell carcinomas.2014

    • Author(s)
      Mikami S, Mizuno R, Kosaka T, Saya H, Oya M and Okada Y
    • Journal Title

      Int J Cancer

      Volume: 136 Issue: 7 Pages: 1504-1514

    • DOI

      10.1002/ijc.29137

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio for Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.2014

    • Author(s)
      Tanaka N, Kikuchi E, Kanao K, Matsumoto K, Shirotake S, Miyazaki Y, Kobayashi H, Kaneko G, Hagiwara M, Ide H, Obata J, Hoshino K, Hayakawa N, Kosaka T, Hara S, Oyama M, Momma T, Nakajima Y, Jinzaki M, Oya M
    • Journal Title

      Ann Surg Oncol

      Volume: 21(12) Issue: 12 Pages: 4041-8

    • DOI

      10.1245/s10434-014-3830-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visceral obesity is associated with better recurrence-free survival after curative surgery for Japanese patients with localized clear cell renal cell carcinoma.2014

    • Author(s)
      Kaneko G, Miyajima A, Yuge K, Yazawa S, Mizuno R, Kikuchi E, Jinzaki M, Oya M
    • Journal Title

      Jpn J Clin Oncol

      Volume: 45(2) Issue: 2 Pages: 210-6

    • DOI

      10.1093/jjco/hyu193

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical efficacy and prognostic factors of tumor progression in Japanese patients with advanced renal cell carcinoma treated with sorafenib.2014

    • Author(s)
      Kondo T, Nakazawa H, Oya M, Kimura G, Fujii Y, Hatano T, Kawata N, Kume H, Morita M, Nakajima K, Ohno Y, Okegawa T, Takahashi S, Wakumoto Y, Horie S
    • Journal Title

      Jpn J Clin Oncol

      Volume: 45(3) Issue: 3 Pages: 274-80

    • DOI

      10.1093/jjco/hyu200

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of an adjuvant chemotherapeutic regimen on the clinical outcome in high-risk patients with upper tract urothelial carcinoma: A Japanese multi-institution experience.2014

    • Author(s)
      Shirotake S, Kikuchi E, Tanaka N, Matsumoto K, Miyazaki Y, Kobayashi H, Ide H, Obata J, Hoshino K, Kaneko G, Hagiwara M, Kosaka T, Kanao K, Kodaira K, Hara S, Oyama M, Momma T, Miyajima A, Nakagawa K, Hasegawa S, Nakajima Y, Oya M
    • Journal Title

      J Urol

      Volume: 193(4) Issue: 4 Pages: 1122-8

    • DOI

      10.1016/j.juro.2014.10.022

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of aryl hydrocarbon receptor promotes invasion of clear cell renal cell carcinoma and is associated with poor prognosis and cigarette smoke.2014

    • Author(s)
      Ishida M, Mikami S, Shinojima T, Kosaka T, Mizuno R, Kikuchi E, Miyajima A, Okada Y, Oya M
    • Journal Title

      Int J Cancer

      Volume: Epub ahead of print Issue: 2 Pages: 299-310

    • DOI

      10.1002/ijc.29398

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activity of axitinib in patients with metastatic renal cell carcinoma previously treated with both vascular endothelial growth factor receptor tyrosine-kinase inhibitor and mammalian target of rapamycin inhibitor.2014

    • Author(s)
      Mizuno R, Miyajima A, Oya M.
    • Journal Title

      Int J Urol.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Renal angiomyolipoma: a radiological classification and update on recent developments in diagnosis and management.2014

    • Author(s)
      Jinzaki M, Silverman SG, Akita H, Nagashima Y, Mikami S,Oya M.
    • Journal Title

      Abdom Imaging.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Renal cell carcinoma in patients with acquired cystic disease of the kidney:Assessment using a combination of T2-weighted, diffusion-weighted, and chemical-shift MRI without the use of contrast material.2014

    • Author(s)
      Akita H, Jinzaki M, Akita A, Mikami S, Oya M, Kuribayashi S.
    • Journal Title

      J Magn Reson Imaging

      Volume: 39(4) Issue: 4 Pages: 924-30

    • DOI

      10.1002/jmri.24226

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Invasion and metastasis of renal cell carcinoma.2013

    • Author(s)
      Mikami S, Oya M, Mizuno R, Kosaka T, Katsube KI, Okada Y.
    • Journal Title

      Med Mol Morphol.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK and mTOR inhibitions in renal cancer cells2013

    • Author(s)
      K. Suzuki, R. Mizuno, K. Suenaga, T. Teruya, N. Tanaka, T. Kosaka, M. Oya
    • Journal Title

      Cancer Medicine

      Volume: 2 Issue: 1 Pages: 32-39

    • DOI

      10.1002/cam4.53

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of a novel nuclear factor-кB activation inhibitor on renal ischemia-reperfusion injury.2013

    • Author(s)
      Kono H, Nakagawa K, Morita S, Shinoda K, Mizuno R, Kikuchi E, Miyajima A, Umezawa K, Oya M.
    • Journal Title

      Transplantation.

      Volume: 96(10) Issue: 10 Pages: 863-70

    • DOI

      10.1097/tp.0b013e3182a3df74

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.2012

    • Author(s)
      Mizuno R, Asano K, Oya M, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 42(5) Pages: 442-446

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of high nuclear grade in patients with pathologic T1a renal cell carcinoma.2012

    • Author(s)
      Suzuki K, Mizuno R, Oya M, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 42(9) Pages: 831-835

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visceral obesity is a strong predictor of perioperative outcome in patients undergoing laparoscopic radical nephrectomy.2012

    • Author(s)
      Hagiwara M, Miyajima A, Oya M, et al.
    • Journal Title

      BJU Int

      Volume: 110

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The benefit of laparoscopic partial nephrectomy in high body mass index patients.2012

    • Author(s)
      Kaneko G, Miyajima A, Oya M, et al.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 42(7) Pages: 619-624

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Efficacy of axitinib in patients with metastatic renal cell carcinoma previously treated with both VEGFR-TKI and mTORI.2014

    • Author(s)
      Mizuno R , Kosaka T, Mikami S, Oya M
    • Organizer
      2014 ASCO Annual Meeting
    • Place of Presentation
      Chicago, The United States of America
    • Year and Date
      2014-05-30 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dose adjustment of axitinib based on AUC monitoring in sunitinib-refractory advanced renal cell carcinoma.2014

    • Author(s)
      Miura Y, Chiyo K, Imamura, Uchino K, Kishida T, Matsubara N, Shinojima T, Oya M, Nakaigawa N, Yoshimura K, Takano T, Tanigawara Y
    • Organizer
      2014 ASCO Annual Meeting
    • Place of Presentation
      Chicago, The United States of America
    • Year and Date
      2014-05-30 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Increased expression of aryl hydrocarbon receptor in clear cell renal cell carcinoma and infiltrating lymphocytes: Implications for cancer invasion, prognosis and tumor immunity.2014

    • Author(s)
      Ishida M, Mikami S, Kosaka T, Mizuno R, Kikuchi E, Miyajima A, Nakagawa K, Okada Y, Oya M
    • Organizer
      AUA2014 Annual Meeting
    • Place of Presentation
      Orlando,The United States of America
    • Year and Date
      2014-05-16 – 2014-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Prognostic significance of TNF-α and CD44 expression in crear cell renal cell carcinomas: implication of cancer invasion, metastasis, and resistance to sunitinib treatment.2014

    • Author(s)
      Mikami S, Mizuno R, Kosaka T, Saya H, Oya M, Okada Y
    • Organizer
      AUA2014 Annual Meeting
    • Place of Presentation
      Orlando, The United States of America
    • Year and Date
      2014-05-16 – 2014-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Visceral obesity is a useful predictor of better recurrence-free survival after curative surgeries for Japanese patients with localized clear cell renal cell carcinoma.2014

    • Author(s)
      Kaneko G, Miyajima A, Hasegawa R, Mizuno R, Uchida Y, Hara S, Kikuchi E, Nakagawa K, Jinzaki M, Oya M
    • Organizer
      29th Annual EAU Congress
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2014-04-11 – 2014-04-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] mTOR pathway regulates the expression of angiotensin 2 type 1 receptor in renal cell carcinoma2013

    • Author(s)
      Kaneko G, Miyajima A, Kosaka T, Mizuno R, Kikuchi E, Oya M.
    • Organizer
      The 108th American Urological Association Annual Meeting
    • Place of Presentation
      San Diego
    • Related Report
      2013 Annual Research Report
  • [Presentation] Clinical Experience of Xp11.2 Translocation Renal Cell Carcinoma2013

    • Author(s)
      Mizuno R, Asanuma H, Kono H, Shinojima T, Kikuchi E, Miyajima A, Nakagawa K, Oya M, Mikami S.
    • Organizer
      33rd CONGRESS OF THE SOCIETE INTERNATIONALE D'UROLOGIE
    • Place of Presentation
      VANCOUVER
    • Related Report
      2013 Annual Research Report
  • [Presentation] C-REACTIVE protein indepently predicts the prognosis of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy: A multiinstitutional study.2013

    • Author(s)
      Obata J, Kikuchi E, Tanaka N, Ishioka K, Shirotake S, Matsumoto K, Kobayashi H, Miyazaki Y, Ide H, Hayakawa N, Ito Y, Kanao K, Miyajima A, Momma T, Nakagawa K, Ueno M, Oya M.
    • Organizer
      The 108th American Urological Association Annual Meeting.
    • Place of Presentation
      San Diego
    • Related Report
      2013 Annual Research Report
  • [Presentation] Tumor necrosis factoralpha induces epithelial-mesenchymal transition and expression of CD44 in renal cell carcinoma : implications for cancer invasion, metastasis and resistance to the sunitinib treatment2012

    • Author(s)
      Oya M, Mikami S, Mizuno R, et al.
    • Organizer
      28th Annual Urological Research Society Meeting
    • Place of Presentation
      大阪
    • Year and Date
      2012-10-04
    • Related Report
      2012 Annual Research Report
  • [Presentation] Long-term outcomes of children with Xp11.2 translocation renal cell carcinoma.2012

    • Author(s)
      Asanuma H, Mizuno R, Oya M, et al.
    • Organizer
      ASCO Annual Meeting
    • Place of Presentation
      Chicago
    • Year and Date
      2012-06-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] Bisebromoamide, as a novel molecular target drug inhibiting phosphorylation of both extracellular signal-regulated kinase and akt in renal cell carcinoma.2012

    • Author(s)
      Suzuki K, Mizuno R, Oya M, et al.
    • Organizer
      The107th American Urological Association Annual Meeting
    • Place of Presentation
      Atlanta
    • Year and Date
      2012-05-20
    • Related Report
      2012 Annual Research Report
  • [Book] Year Book of RCC20132013

    • Author(s)
      水野隆一、大家基嗣
    • Total Pages
      207
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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