The importance of regulation of the tumor microenvironment in cisplatin-resistant urothelial carcinoma

• Project/Area Number: 15K20110
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Keio University
• Principal Investigator: Niwa Naoya 慶應義塾大学, 医学部(信濃町), 助教 (40626743)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 尿路上皮癌 / 癌微小環境 / 上皮間葉転換 / シスプラチン / 抗癌剤耐性 / 抗癌剤 / TNFAIP2 / 抗がん剤耐性 / がん微小環境

Outline of Final Research Achievements

Knockdown and overexpression of TNF-alpha induced protein 2 (TNFAIP2) in 5637 and its subline 5637PR with acquired platinum resistance resulted in suppression and overexpression of epithelial-mesenchymal transition related proteins, respectively. Immunohistochemical analysis in surgical specimens revealed that the expression of TNFAIP2 is significantly associated with oncologic outcome in patients with urothelial carcinoma. Moreover, overexpression and suppression of TNFAIP2 resulted in promotion and inhibition of cancer cells, respectively. These results suggested the importance of the regulation of the tumor microenvironment by targeting TNFAIP2 and its potential as a new therapeutic target.

Research Products

• [Journal Article] Are the Formulas Used to Estimate Renal Function Adequate for Patients Treated With Cisplatin-Based Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Carcinoma? (2016)
  • Author(s): Naoya Niwa, Eiji Kikuchi, Masashi Matsushima, Nobuyuki Tanaka, Toru Nishiyama T, Akira Miyajima, Shiro Saito, Mototsugu Oya
  • Journal Title: Clinical Genitourinary Cancer. Volume: 14 Issue: 5 Pages: e501-e507
  • DOI: 10.1016/j.clgc.2016.04.018
  • Peer Reviewed
• [Journal Article] Acquired platinum resistance involves epithelial-to-mesenchymal transition through ubiquitin ligase FBXO32 dysregulation (2016)
  • Author(s): Tanaka N, Kosaka T, Miyazaki Y, Mikami S, Niwa N, Otsuka Y, Minamishima YA, Mizuno R, Kikuchi E, Miyajima A, Sabe H, Okada Y, Uhlen P, Suematsu M, Oya M
  • Journal Title: JCI insight Volume: 1 Issue: 18
  • DOI: 10.1172/jci.insight.83654
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with initially diagnosed TaG1-2 bladder cancers: A matched-pair analysis (2015)
  • Author(s): Naoya Niwa, Kazuhiro Matsumoto, Nozomi Hayakawa, Yujiro Ito, Takahiro Maeda, Seiya Akatsuka, Takeshi Masuda, So Nakamura, Nobuyuki Tanaka
  • Journal Title: Urologic Oncology: Seminars and Original Investigations Volume: 33 Issue: 9 Pages: 386.e15-386.e21
  • DOI: 10.1016/j.urolonc.2015.04.018
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Are calculated formulas for estimating renal function adequate for administered cisplatin-based chemotherapy in solitary renal patients after nephroureterectomy for upper tract urothelial carcinoma? (2016)
  • Author(s): Naoya Niwa, Eiji Kikuchi, Masashi Matsushima, Nobuyuki Tanaka, Toru Nishiyama, Akira Miyajima, Shiro Saito, Mototsugu Oya.
  • Organizer: 2016年米国泌尿器科学会
  • Place of Presentation: サンディエゴ
  • Year and Date: 2016-05-07
  • Int'l Joint Research
• [Presentation] Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with low- or intermediate-risk non-muscle invasive bladder cancer (2016)
  • Author(s): Naoya Niwa, Kazuhiro Matsumoto, Nobuyuki Tanaka, Nozomi Hayakawa, Yujiro Ito, Takahiro Maeda, Seiya Akatsuka, Takeshi Masuda, So Nakamura, Mototsugu Oya.
  • Organizer: 2016年米国泌尿器科学会
  • Place of Presentation: サンディエゴ
  • Year and Date: 2016-05-07
  • Int'l Joint Research
• [Remarks] 慶應義塾大学医学部泌尿器科学教室ホームページ
  • URL: http://www.keio-urology.jp/
• [Remarks] 慶應義塾大学医学部泌尿器科学教室
  • URL: http://www.keio-urology.jp/