Development of bladder cancer early diagnosis and treatment method using the CXCR4-beta arrestin2-ERK pathway

• Project/Area Number: 23592330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: University of Tsukuba
• Principal Investigator: NISHIYAMA Hiroyuki 筑波大学, 医学医療系, 教授 (20324642)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Jun 筑波大学, 医学医療系, 准教授 (10550246) ; OIKAWA Takehiro 筑波大学, 医学医療系, 講師 (00361345) ; SUETOMI Takahiro 筑波大学, 医学医療系, 講師 (10574650)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: CXCR4 / ARRB2 / TXNIP / bladder / carcinogenesis / 尿路上皮癌 / βarrestin2 / 膀胱癌早期診断治療法 / BBN / EMT / E cadherin

Research Abstract

The result of gene and protein expression of CXCR4-ERK pathway and TXNIP-ARRB2 pathway in mouse bladder cancer model and bladder cancer cell lines. We indicate that TXNIP negatively regulates bladder carcinogenesis by attenuating SDF-1-CXCR4-induced ERK activation. This signal transduction
pathway can be a potent target in preventing or treating bladder cancer.

Research Products

• [Journal Article] The Transcription Factor Sp3 Regulates the Expression of a Metastasis-Related Marker of Sarcoma, Actin Filament-Associated Protein 1-Like 1 (AFAP1L1). (2013)
  • Author(s): Kajita Y, Kato T Jr, Tamaki S, Furu M, Takahashi R, Nagayama S, Aoyama T, Nishiyama H, Nakamura E, Katagiri T, Nakamura Y, Ogawa O, Toguchida J.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e49709-e49709
  • DOI: 10.1371/journal.pone.0049709
  • Peer Reviewed
• [Journal Article] Assessment and Management of Renal Impairment in Chemotherapy for Urogenital Cancer (2013)
  • Author(s): Kawai K, Ichioka D, Inai H, Miyazaki J, Nishiyama H
  • Journal Title: Jpn J Clin Oncol Volume: 12 Issue: 11 Pages: 1055-1063
  • DOI: 10.1093/jjco/hyt132
  • Peer Reviewed
• [Journal Article] Adverse Reactions Related to Treatment Compliance During BCG Maintenance Therapy for Non-muscle-invasive Bladder Cancer (2013)
  • Author(s): Miyazaki J, Hinotsu S, Ishizuka N, Naito S, Ozono S, Akaza H, Nishiyama H
  • Journal Title: Jpn J Clin Oncol[Epub ahead of print] Volume: 43(8) Issue: 8 Pages: 34-827
  • DOI: 10.1093/jjco/hyt086
  • Peer Reviewed
• [Journal Article] Risk factors for intravesical recurrence in patients with high-grade T1 bladder cancer in the second TUR era (2013)
  • Author(s): Takaoka E, Miyazaki J, Kawai K, Nishiyama H.
  • Journal Title: Int. J Urol Volume: 20(7) Issue: 4 Pages: 22-716
  • DOI: 10.1093/jjco/hyt016
  • Peer Reviewed
• [Journal Article] Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy (2013)
  • Author(s): Kimura T, Onozawa M, Miyazaki J, Kawai K, Nishiyama H, Hinotsu S, Akaza H
  • Journal Title: Int J Uro Volume: 20(9) Issue: 9 Pages: 8-880
  • DOI: 10.1111/iju.12064
  • NAID: 10031195889
  • Peer Reviewed
• [Journal Article] Risk factors for chronic kidney disease after chemotherapy for testicular cancer (2013)
  • Author(s): Inai H, Kawai K, Ikeda A, Ando S, Kimura T, Oikawa T, Onozawa M, Miyazaki J, Uchida K, Nishiyama H
  • Journal Title: Int J Urol Volume: 20(7) Issue: 7 Pages: 22-716
  • DOI: 10.1111/iju.12017
  • NAID: 10031190521
  • Peer Reviewed
• [Journal Article] Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: current understanding and perspectives on engineered BCG vaccine. (2013)
  • Author(s): Kawai K, Miyazaki J, Joraku A, Nishiyama H, Akaza H.
  • Journal Title: Cancer Sci. Volume: 104 Issue: 1 Pages: 22-27
  • DOI: 10.1111/cas.12075
  • Peer Reviewed
• [Journal Article] Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts (2013)
  • Author(s): Shimazui T, Yoshikawa K, Miyazaki J, Kojima T, Inai H, Ando S, Uemura H, Uchida K, Nishiyama H
  • Journal Title: Int. J. Oncol Volume: Vo l .42 Issue: 2 Pages: 543-54
  • DOI: 10.3892/ijo.2012.1752
  • Peer Reviewed
• [Journal Article] Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy (2012)
  • Author(s): Yamasaki T, Nishiyama H.
  • Journal Title: Cancer Sci Volume: 103(11) Pages: 37-2027
  • Peer Reviewed
• [Journal Article] Overexpression of ETS-1 is associated with malignant biological features of prostate cancer (2012)
  • Author(s): Li B, Nishiyama H
  • Journal Title: Asian J Androl Volume: 14(6) Pages: 3-860
  • NAID: 120005289841
  • Peer Reviewed
• [Journal Article] Analysis of Intravesical Recurrence After Bladder-preserving Therapy for Muscle-invasive Bladder Cancer (2012)
  • Author(s): Onozawa M, Miyazaki J, Kawai K, Nishiyama H
  • Journal Title: JJCO Volume: 42(9) Issue: 9 Pages: 30-825
  • DOI: 10.1093/jjco/hys105
  • Peer Reviewed
• [Journal Article] Management of ureteral obstruction in advanced testicular tumor with lymph node metastasis (2012)
  • Author(s): Ikeda A, Kawai K, Miyazaki J, Nishiyama H.
  • Journal Title: Jpn J Clin Oncol Volume: 42(8) Issue: 8 Pages: 52-748
  • DOI: 10.1093/jjco/hys094
  • NAID: 120007137102
  • Peer Reviewed
• [Journal Article] A novel animal model of underactive bladder : Analysis of lower urinary tract function in a rat lumbar canal stenosis model (2012)
  • Author(s): Sekido N, Joraku A, Okada H, Wakamatsu D, Matsuya H, Nishiyama H
  • Journal Title: Neurourol Urodyn Volume: 31(7) Issue: 7 Pages: 6-1190
  • DOI: 10.1002/nau.21255
  • Peer Reviewed
• [Journal Article] Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice (2012)
  • Author(s): Masuda T, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 27 Pages: 10885-108901
  • DOI: 10.1073/pnas.1121524109
  • Peer Reviewed
• [Journal Article] Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer (2012)
  • Author(s): Saito R, Nishiyama H
  • Journal Title: Oncogene Volume: 26
  • Peer Reviewed
• [Journal Article] JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma (2012)
  • Author(s): Kanno T, Nishiyama H
  • Journal Title: Oncogene Volume: 31(25) Pages: 110-3098
  • Peer Reviewed
• [Journal Article] Thioredoxin-interacting protein suppresses bladder carcinogenesis (2011)
  • Author(s): Nishizawa K, Nishiyama H
  • Journal Title: Carcinogenesis Volume: 32(10) Issue: 10 Pages: 66-1459
  • DOI: 10.1093/carcin/bgr137
  • NAID: 120004397865
  • Peer Reviewed
• [Journal Article] The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder carcinoma (2011)
  • Author(s): Miyazaki J, Nishiyama H, Kawai K
  • Journal Title: Anticancer Res Volume: 31(6) Pages: 71-2065
  • URL: http://ar.iiarjournals.org/content/31/6/2065.long
  • Peer Reviewed
• [Journal Article] A polymorphism of the POLG2 gene is genetically associated with the invasiveness of urinary bladder cancer in Japanese males (2011)
  • Author(s): Ratanajaraya C, Nishiyama H
  • Journal Title: J Hum Genet., Epub ahead of print
  • NAID: 10030660404
  • Peer Reviewed
• [Journal Article] Thioredoxin-interacting protein suppresses bladder carcinogenesis (2011)
  • Author(s): Koji Nishizawa, Hiroyuki Nishiyama, et al.
  • Journal Title: Carcinogenesis Volume: 32 Pages: 1459-1466
  • NAID: 120004397865
  • Peer Reviewed