Development of novel diagnostic procedure for detection of upper urinary tract urothelial cancer

• Project/Area Number: 16K11010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyushu University
• Principal Investigator: Inokuchi Junichi 九州大学, 大学病院, 講師 (10403924)
• Co-Investigator(Kenkyū-buntansha): 村田 正治 九州大学, 先端医療イノベーションセンター, 特任教授 (30304744) ; 片山 佳樹 九州大学, 工学研究院, 教授 (70284528) ; 姜 貞勲 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50423512) ; 清島 圭二郎 九州大学, 大学病院, 講師 (80444818)
• Research Collaborator: Grollman Arthur P. Stony Brook University, Laboratory of Chemical Biology
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 上部尿路癌 / 腎盂癌 / 尿管癌 / アリストロキア酸 / 癌診断 / 腫瘍学 / 泌尿器科学 / 尿路上皮癌 / 膀胱癌 / 医療・福祉 / 癌

Outline of Final Research Achievements

We hypothesized that a fraction of upper urinary tract urothelial carcinoma (UTUC) cases in Japan might result from past intake of aristolochic acid (AA), a powerful nephrotoxin and human carcinogen, which cause UTUC. In contrast to the high incidence of AA-associated UTUC in Taiwan cohort, our study indicated that confirmed AA-exposure in Japanese UTUC patients were rare.
We examined the efficacy of activated protein kinase X in urine sample to detect urothelial cancer. We found the high sensitivity and specificity of this assay, and suggested the activated protein kinase X as promising biomarker for detecting urothelial cancer.

Academic Significance and Societal Importance of the Research Achievements

上部尿路がんを含めて、様々ながん腫において人種差、地域差があることがわかっている。生薬成分の一つであるアリストロキア酸の摂取は上部尿路がんの発がんと関連が指摘されているが、今回の研究にて本邦においてはその頻度が稀であることが示された。また、尿路上皮がんの診断において、体の負担の軽い尿を用いたリン酸化酵素Xを標的とした新たな診断法が、高い感度、特異度を示し、有望な検査法となりうることが明らかとなった。

Research Products

• [Int'l Joint Research] Stony Brook University/University of Minnesota(米国)
• [Journal Article] A rational risk assessment for intravesical recurrence in primary low-grade Ta bladder cancer: A retrospective analysis of 245 cases. (2018)
  • Author(s): Akitake M, Kiyoshima K, Yokomizo A, Shiga K, Koga H, Takeuchi A, Shiota M, Inokuchi J, Tatsugami K, Yamaguchi A, Eto M.
  • Journal Title: Mol Clin Oncol. Volume: 8 Pages: 785-790
  • DOI: 10.3892/mco.2018.1602
  • Peer Reviewed / Open Access
• [Journal Article] Role of lymph node dissection during radical nephroureterectomy for upper urinary tract urothelial cancer: multi-institutional large retrospective study JCOG1110A. (2017)
  • Author(s): Inokuchi J, Kuroiwa K, Kakehi Y, Sugimoto M, Tanigawa T, Fujimoto H, Gotoh M, Masumori N, Ogawa O, Eto M, Ohyama C, Yamaguchi A, Matsuyama H, Ichikawa T, Asano T, Mizusawa J, Eba J, Naito S
  • Journal Title: World J Urol. Volume: 35 Issue: 11 Pages: 1737-1744
  • DOI: 10.1007/s00345-017-2049-x
  • Peer Reviewed
• [Journal Article] Impact of lymph node dissection on clinical outcomes during nephroureterectomy in patients with clinically node-negative upper urinary tract urothelial cancer: subanalysis of a multi-institutional nationwide case series of the Japanese Urological Association (2017)
  • Author(s): Inokuchi Junichi、Eto Masatoshi、Hara Tomohiko、Fujimoto Hiroyuki、Nishiyama Hiroyuki、Miyazaki Jun、Kikuchi Eiji、Hinotsu Shiro、Koie Takuya、Ohyama Chikara
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 47 Issue: 7 Pages: 652-659
  • DOI: 10.1093/jjco/hyx051
  • Peer Reviewed / Open Access
• [Journal Article] An In Vitro Study of a New Device: Evaluation of Novel Wide-Angle Lens Flexible Cystoscope Using Phantom Bladder Model. (2017)
  • Author(s): Yamaguchi K, Inoue T, Habuchi T, Inokuchi J, Yokomizo A, Eto M, Kanayama HO.
  • Journal Title: J Endourol. Volume: 31 Issue: 10 Pages: 1073-1078
  • DOI: 10.1089/end.2017.0371
  • Peer Reviewed
• [Journal Article] Diversity in treatment modalities of Stage II/III urothelial cancer in Japan: sub-analysis of the multi-institutional national database of the Japanese Urological Association. (2016)
  • Author(s): Koie T, Ohyama C, Fujimoto H, Nishiyama H, Miyazaki J, Hinotsu S, Kikuchi E, Sakura M, Inokuchi J, Hara T
  • Journal Title: Jpn J Clin Oncol. Volume: 46 Issue: 5 Pages: 468-474
  • DOI: 10.1093/jjco/hyw005
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Significance of Preoperative Urine Cytology in Low-grade Non-muscle-invasive Bladder Cancer. (2016)
  • Author(s): Kiyoshima K, Akitake M, Shiota M, Takeuchi A, Takahashi R, Inokuchi J, Tatsugami K, Yokomizo A, Eto M.
  • Journal Title: Anticancer Res. Volume: 36 Pages: 799-802
  • Peer Reviewed
• [Journal Article] Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. (2016)
  • Author(s): Miyazaki J, Nishiyama H, Fujimoto H, Ohyama C, Koie T, Hinotsu S, Kikuchi E, Sakura M, Inokuchi J, Hara T.
  • Journal Title: J Endourol. Volume: 30 Issue: 5 Pages: 520-525
  • DOI: 10.1089/end.2015.0757
  • Peer Reviewed
• [Presentation] 本邦におけるアリストロキア酸に起因する上部尿路癌の実態 (2019)
  • Author(s): 猪口淳一、Kathleen G. Dickman, Arthur P. Grollman, Robert J. Turesky, Jiri. Zavadil, 森谷正明,潮田真己、立神勝則、内藤誠二、江藤正俊
  • Organizer: 第107回日本泌尿器科学会総会
• [Book] PROTEIN KINASE C EMERGING ROLES AND THERAPEUTIC POTENTIAL (2018)
  • Author(s): Jeong-Hun Kang, Junichi Inokuchi, Takahito Kawano and Masaharu Murata
  • Total Pages: 90
  • Publisher: Nova Science Publishers
  • ISBN: 9781536132113