Molecular Analysis of Rare Renal Cell Carcinoma and Identification of Molecular Therapeutic Targets

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659752
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: HABUCHI Tomonori 秋田大学, 医学(系)研究科(研究院), 教授 (00293861)
• Co-Investigator(Kenkyū-buntansha): OHYAMA Chikara 弘前大学, 医学系研究科, 教授 (80282135) ; MIMATA Hiromitsu 大分大学, 医学部, 教授 (60219714) ; NARITA Shintaro 秋田大学, 医学部, 講師 (40396552) ; NANJO Hiroshi 秋田大学, 医学部, 准教授 (70250892)
• Project Period (FY): 2011 – 2013
• Keywords: 腎細胞癌 / Xp転座型腎細胞癌 / TFE3 / FISH / 分子標的薬 / 紡錘型腎細胞癌

Research Abstract

Molecular mechanisms of common renal cell carcinoma have been delineated by recent extensive studies. On the other hand, molecular mechanisms remain largely unknown regarding renal cell carcinoma with Xp-translocation, which is rather frequent in young patients. We tried to delineate the molecular mechanisms underlying renal cell carcinoma with Xp-translocation and to identify molecular therapeutic targets in this multi-institutional study.
By analyzing 280 patients with renal cell carcinoma, we found that 4.3% of renal cell carcinoma was immunohistologically positive for TFE3 protein. By establishing TFE3-gene FISH, we showed that most of TFE-positive tumors harbor Xp-translocation. Finally, we analyzed the clinical and pathological data of the patients with FISH-positive tumors.

Research Products

• [Journal Article] Organ-specific and tumor-size dependent responses to sunitinib in clear cell renal cell (2014)
  • Author(s): Tsuchiya N, Yuasa T, Maita S, Narita S, Inoue T, Numakura K, Saito M, Satoh S, Yonese J, Habuchi T
  • Journal Title: BMC Urol Volume: 14(1) Pages: 26
  • DOI: 10.1186/1471-2490-14-26.
• [Journal Article] Serum N-glycan alteration associated with renal cell carcinoma detected by high-throughput glycan analysis (2014)
  • Author(s): Hatakeyama S, Amano M, Tobisawa Y, Yoneyama T, Tsuchiya N, Habuchi T, Nishimura SI, Ohyama C
  • Journal Title: J Urol Volume: 191(3) Pages: 805-13
  • DOI: 10.1016/j.juro.2013.10.052.
• [Journal Article] Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis (2013)
  • Author(s): Tsuchiya N, Narita S, Inoue T, Saito M, Numakura K, Huang M, Hatakeyama S, Satoh S, Saito S, Ohyama C, Arai Y, Ogawa O, Habuchi T
  • Journal Title: BMC Cancer Volume: 25;13 Pages: 150
• [Journal Article] Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma (2013)
  • Author(s): Tsuchiya N, Narita S, Inoue T, Hasunuma N, Numakura K, Horikawa Y, Satoh S, Notoya T, Fujishima N, Hatakeyama S, Ohyama C, Habuchi T
  • Journal Title: Anticancer Drugs Volume: 24(3) Pages: 310-4
• [Journal Article] Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function (2012)
  • Author(s): Maita S, Yuasa T, Tsuchiya N, Mitobe Y, Narita S, Horikawa Y, Hatake K, Fukui I, Kimura S, Maekawa T, Habuchi T
  • Journal Title: Int J Cancer Volume: 130(3) Pages: 677-84
  • DOI: 10.1002/ijc.26034.
• [Journal Article] MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis (2012)
  • Author(s): Suzuki Y, Sutoh M, Hatakeyama S, Mori K, Yamamoto H, Koie T, Saitoh H, Yamaya K, Funyu T, Habuchi T, Arai Y, Fukuda M, Ohyama C, Tsuboi S
  • Journal Title: Int J Oncol Volume: 40(6) Pages: 1831-8
  • DOI: 10.3892/ijo.2012.1411.
• [Journal Article] Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib (2012)
  • Author(s): Yuasa T, Tsuchiya N, Urakami S, Horikawa Y, Narita S, Inoue T, Saito M, Yamamoto S, Yonese J, Fukui I, Nakano K, Takahashi S, Hatake K, Habuchi T.
  • Journal Title: BJU Int Volume: 109(9) Pages: 1349-54
• [Journal Article] A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib (2011)
  • Author(s): Numakura K, Tsuchiya N, Yuasa T, Saito M, Obara T, Tsuruta H, Narita S, Horikawa Y, Satoh S, Habuchi T
  • Journal Title: Int J Clin Oncol Volume: 16(5) Pages: 577-80
  • DOI: 10.1007/s10147-010-0154-6.
• [Presentation] Risk factors for sorafenib-induced erythema multiforme in Japanese patients with advanced renal cell carcinoma (2012)
  • Author(s): Tsuchiya, N., Narita, S., Inoue, T., Hasunuma, N., Numakura, K., Horikawa, Y., Satoh, S., Notoya, T., Fujishima, N., Hatakeyama, S., Ohyama, C., Habuchi, T
  • Organizer: The 32nd Congress of the Societe Internationale d'Urologie
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20120900-1000
• [Presentation] Stimulation of macrophage inhibitory cytokine-1 by palmitic acid activates prostate cancer cell invasiveness (2012)
  • Author(s): Mingguro, H., Narita, S., Maita, S., Numakura, K., Obara, T., Inoue, T., Horikawa, Y., Satoh, S.and Habuchi, T
  • Organizer: The 107th annual meeting of the American Urological Association
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20120500
• [Presentation] 腎細胞癌患者におけるソラフェニブによる多形紅斑とHLA型との関連性の検討 (2012)
  • Author(s): 土谷順彦,堀川洋平,成田伸太郎,井上高光,小原崇,沼倉一幸,米田真也,佐藤滋,能登谷武,藤島直仁,藤山信弘,三浦昌朋,畠山真吾,大山力,羽渕友則
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20120400
• [Presentation] 転移性腎細胞癌に対するmTOR inhibitor を含むSequential Therapy の経験 (2012)
  • Author(s): 井上高光、米田真也、沼倉一幸、小原 崇、成田伸太郎、堀川洋平、土谷順彦、佐藤 滋、羽渕友則
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20120400
• [Presentation] 分子標的薬時代の腎癌の治療戦略 -Sequential に使いこなす- (2011)
  • Author(s): 羽渕友則
  • Organizer: 第63回日本泌尿器科学会西日本総会
  • Place of Presentation: 久留米市
  • Year and Date: 20111100
• [Presentation] Xp11.2 転座をともなう腎細胞癌 (2011)
  • Author(s): 沼倉一幸、土谷順彦、畠山真吾、大山 力、井上 亨、三股浩光、齋藤英郎、荒井陽一、寒野 徹、神波大己、小川 修、羽渕友則
  • Organizer: 第76回日本泌尿器科学会東部総会
  • Place of Presentation: 横浜
  • Year and Date: 20111000
• [Presentation] Clinical Characteristics of Xp11.2 Translocation Renal Cell Carcinoma in Japanese Adult Patients (2011)
  • Author(s): Numakura, K., Tsuchiya, N., Yuasa, T., Inoue, T., Narita, S., Horikawa, Y., Hatakeyama, S., Ohyama, C., Inoue, T., Mimata, H., Saito, H., Arai, Y., Kanno, T., Kamba, T., Ogawa, O., Habuchi, T
  • Organizer: The 106th Annunal Meeting of the American Urological Association
  • Place of Presentation: Washisnton DC, USA
  • Year and Date: 20110500
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html