膀胱癌に対する抗体検出に付随する新規腫瘍マーカーの解析

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24592408
• Research Institution: Kitasato University
• Principal Investigator: 松本 和将 北里大学, 医学部, 講師 (70306603)
• Co-Investigator(Kenkyū-buntansha): 佐藤 雄一 北里大学, 医療衛生学部, 教授 (30178793) ; 佐藤 威文 北里大学, 医学部, 講師 (50286332)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 膀胱癌 / 尿路上皮癌 / 腫瘍マーカー / 蛋白質

Outline of Annual Research Achievements

本研究費を受諾することで、膀胱癌（尿路上皮癌）の腫瘍マーカーの探索を遂行してきた。膀胱癌特異的単クローン性抗体を600個、膀胱癌患者血清中の自己抗体が認識する腫瘍関連蛋白質163個を同定した。一次スクリーニングを行うことで膀胱癌特異的抗体を204個、自己抗体を138個獲得した。検出蛋白質のうち膀胱癌と臨床病理学的な相関関係が認められたものが数多く得られた。本年度においては、膀胱癌特異的蛋白としてnestin、periplakinを、血清蛋白としてS100A6、自己抗体としてMMP2、calreticulinを同定した。Nestin、periplakinにおいては手術標本を用いた免疫染色の検討を行った。Nestinは進行癌で発現が増強し、生命予後も不良であった。また、periplakinは進行癌で発現が消失し、生命予後も不良であった。加えて、血清periplakinの膀胱癌症例での動態を検討し、健常者と比較し膀胱癌症例での発現が有意に低下していた。本蛋白質は血清マーカーとして膀胱癌の検出に利用できる可能性を示唆していた。血清S100A6は健常者と比較し膀胱癌症例で発現有意に上昇しており、治療後など経過観察の腫瘍マーカーのとして有用性を示した。また、自己抗体としてのMMP2、calreticulinについて、膀胱癌症例で有意に上昇していた。膀胱癌に関する自己抗体の存在について始めて報告した。本研究で得られた成果の一部を「膀胱癌の診断」（特願 2015-020750）と題して特許申請を行った。残り多くの膀胱癌に関連する蛋白質を同定しているため、今後さらに検討、適正化を進め、特許取得、臨床への実用化を目指す予定である。

Research Products

• [Journal Article] High expression level of preoperative serum uroplakin III is associated with biologically aggressive bladder cancer. (2015)
  • Author(s): Tsumura H, Matsumoto K, Ikeda M, Yanagita K, Hirano S, Hagiwara M, Nagashio R, Fujita T, Sato Y, Iwamura M.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 16 Pages: 1539-1543
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Conditional survival after radical nephroureterectomy for upper tract carcinoma. (2015)
  • Author(s): Ploussard G, Xylinas E, Lotan Y, Novara G, Margulis V, Roupret M, Matsumoto K, Karakiewicz PI, Montorsi F, Remzi M, Seitz C, Scherr DS, Kapoor A, Fairey AS, Rendon R, Izawa J, Black PC, Lacombe L, Shariat SF, Kassouf W.
  • Journal Title: Eur Urol. Volume: 67 Pages: 803-812
  • DOI: 10.1016/j.eururo.2014.08.003.
  • Peer Reviewed
• [Journal Article] Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castrate-resistant prostate cancer: dose-related immune boosting and suppression. (2015)
  • Author(s): Noguchi M, Arai G, Matsumoto K, Naito S, Moriya F, Suekane S, Komatsu N, Matsueda S, Sasada T, Yamada A, Itoh K.
  • Journal Title: Cancer Immunol Immunother. Volume: 64 Pages: 493-505
  • DOI: 10.1007/s00262-015-1660-1.
  • Peer Reviewed
• [Journal Article] Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy. (2015)
  • Author(s): Matsumoto K, Mochizuki K, Hirayama T, Ikeda M, Nishi M, Tabata K, Okazaki M, Fujita T, Taoka Y, Iwamura M.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 16 Pages: 2483-2487
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical value of dividing false positive urine cytology findings into three categories: atypical, indeterminate and suspicious of malignancy. (2014)
  • Author(s): Matsumoto K, Ikeda M, Hirayama M, Nishi M, Fujita T, Hattori M, Sato Y, Ohbu M, Iwamura M.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 15 Pages: 2251-2255
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nestin is an independent predictor of cancer-specific survival after radical cystectomy in patients with urothelial carcinoma of the bladder. (2014)
  • Author(s): Tabata K, Matsumoto K, Minami S, Ishii D, Nishi M, Fujita T, Saegusa M, Sato Y, Iwamura M.
  • Journal Title: PLOS ONE. Volume: 9 Pages: -
  • DOI: 10.1371/journal.pone.0091548.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Predictors of survival in patients with disease recurrence after radical nephroureterectomy. (2014)
  • Author(s): Kluth LA, Xylinas E, Kent M, Hagiwara M, Kikuchi E, Ikeda M, Matsumoto K, Dalpiaz O, Zigeuner R, Aziz A, Fritsche HM, Deliere A, Raman JD, Bensalah K, Al-Matar B, Gakis G, Novara G, Klatte T, Remzi M, Comploj E, Pycha A, Roupret M, Tagawa ST, Chun FK, Scherr DS, Vickers A, Shariat SF.
  • Journal Title: BJU Int. Volume: 113 Pages: 911-917
  • DOI: 10.1111/bju.12369.
  • Peer Reviewed
• [Journal Article] Loss of periplakin expression is associated with pathological stage and cancer-specific survival in patients with urothelial carcinoma of the urinary bladder. (2014)
  • Author(s): Matsumoto K, Ikeda M, Sato Y, Kuruma H, Kamata Y, Nishimori T, Tomonaga T, Nomura F, Egawa S, Iwamura M.
  • Journal Title: Biomed Res. Volume: 35 Pages: 201-206
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy. (2014)
  • Author(s): Xylinas E, Kluth LA, Rieken M, Lee RK, Elghouayel M, Ficarra V, Margulis V, Lotan Y, Roupret M, Martinez-Salamanca JI, Matsumoto K, Seitz C, Karakiewicz PI, Zerbib M, Scherr DS, Shariat SF.
  • Journal Title: BJU Int. Volume: 114 Pages: 56-61
  • DOI: 10.1111/bju.12400.
  • Peer Reviewed
• [Journal Article] Comparison of radical cystectomy and chemoradiotherapy in patients with locally advanced bladder cancer. (2014)
  • Author(s): Ikeda M, Matsumoto K, Nishi M, Tabata K, Fujita T, Ishiyama H, Hayakawa K, Iwamura M.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 15 Pages: 6519-6524
  • Peer Reviewed / Open Access
• [Journal Article] Conditional survival after radical cystectomy for bladder cancer: evidence for a patient changing risk profile over time. (2014)
  • Author(s): Ploussard G, Shariat SF, Dragomir A, Kluth LA, Xylinas E, Masson-Lecomte A, Rieken M, Rink M, Matsumoto K, Kikuchi E, Klatte T, Boorjian SA, Lotan Y, Roghmann F, Fairey AS, Fradet Y, Black PC, Rendon R, Izawa J, Kassouf W.
  • Journal Title: Eur Urol. Volume: 66 Pages: 361-370
  • DOI: 10.1016/j.eururo.2013.09.050
  • Peer Reviewed
• [Journal Article] Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. (2014)
  • Author(s): Rieken M, Schubert T, Xylinas E, Kluth L, Roupret M, TrinhQD, Lee RK, Al Hussein Al Awamlh B, Fajkovic H, Novara G, Margulis V, Lotan Y, Martinez-Salamanca JI, Matsumoto K, Seitz C, Remzi M, Karakiewicz PI, Scherr DS, Briganti A, Bachmann A, Shariat SF.
  • Journal Title: Eur J Surg Oncol. Volume: 40 Pages: 1693-1699
  • DOI: 10.1016/j.ejso.2014.03.018.
  • Peer Reviewed
• [Journal Article] Serum periplakin as a potential biomarker for urothelial carcinoma of the urinary bladder. (2014)
  • Author(s): Matsumoto K, Ikeda M, Matsumoto T, Nagashio R, Nishimori T, Tomonaga T, Nomura F, Sato Y, Kitasato H, Iwamura M.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 15 Pages: 9927-9931
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum expression of S100A6 is a potential detection marker in patients with urothelial carcinoma in the urinary bladder. (2014)
  • Author(s): Nishi M, Matsumoto K, Kobayashi M, Yanagita K, Matsumoto T, Ryo Nagashio, Ishii D, Fujita T, Sato Y, Iwamura M.
  • Journal Title: Biomed Res. Volume: 35 Pages: 351-356
  • DOI: 10.2220/biomedres.35.351.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy. (2015)
  • Author(s): Xylinas EN, Kluth LA, Rieken M, Scherr DS, Margulis V, Lotan Y, Martinez-Salamanca J, Matsumoto K, Karakiewica PI, Shariat SF.
  • Organizer: 30th Annual European Association of Urology Congress
  • Place of Presentation: Madrid(スペイン)
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] Detection of tumor-associated antigens in culture supernatants using autoantibodies in sera from patients with bladder cancer. (2015)
  • Author(s): Mochizuki K, Matsumoto K, Minami S, Tabata K, Fujita T, Irie A, Yoshida K, Sato Y, Iwamura M.
  • Organizer: 30th Annual European Association of Urology Congress
  • Place of Presentation: Madrid(スペイン)
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] Loss of periplakin expression is associated with pathological stage and cancer-specific survival in patients with urothelial carcinoma of the urinary bladder. (2015)
  • Author(s): Matsumoto K, Hirayama T, Ikeda M, Nishi M, Tsumura H, Fujita T, Irie A, Yoshida K, Sato Y, Iwamura M.
  • Organizer: 30th Annual European Association of Urology Congress
  • Place of Presentation: Madrid(スペイン)
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] 尿路上皮がんにおける腫瘍マーカーの探索 (2015)
  • Author(s): 松本和将
  • Organizer: 第１２回北里疾患プロテオーム研究会・第６５回日本電気泳動学会シンポジウム
  • Place of Presentation: 北里大学(神奈川県相模原市)
  • Year and Date: 2015-03-18
  • Invited
• [Presentation] Salvage chemotherapy としてのGemcitabine/Nedaplatin療法の検討 (2014)
  • Author(s): 松本和将、池田勝臣、平山貴博、西 盛宏、田畑健一、藤田哲夫、岩村正嗣
  • Organizer: 第５２回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] 化学療法抵抗性膀胱がんに対しするがんワクチン療法の第II相無作為比較試験 (2014)
  • Author(s): 野口正典、松本和将、植村天寿、新井 学、江藤正俊、内藤誠二、大山 力、那須保友、田中正利、伊東恭悟
  • Organizer: 第５２回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] Randomized phase II study of personalized peptide vaccination in patients with advanced bladder cancer progressing after chemotherapy. (2014)
  • Author(s): Noguchi M, Matsumoto K, Uemura H, Arai G, Etoh M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, Suekane S, Matsueda S, Komatsu M, Sasada T, Yamada A, Itoh K.
  • Organizer: 50th Annual Meeting of the American Society of Clinical Oncology
  • Place of Presentation: Chicago(アメリカ合衆国)
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Association of perioperative blood transfusion with oncological outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. (2014)
  • Author(s): Rieken M, Schubert T, Xylinas E, Kluth L, Roupret M, Trinh QD, Lee R, Awamlh AI, Fajkovic H, Novara G, Margulis V, Lotan Y, Martinez-Salamanca JI, Matsumoto K, Seitz C, Remz M, Karakiewicz PI, Scherr DS, Briganti A, Bachmann A, Shariat SF.
  • Organizer: 107th Annual Meeting American Urological Association
  • Place of Presentation: Orlando(アメリカ合衆国)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 尿細胞診擬陽性症例に対する臨床的評価について (2014)
  • Author(s): 松本和将、平山貴博、池田勝臣、西 盛宏、田畑健一、藤田哲夫、服部 学、大部誠、岩村正嗣
  • Organizer: 第１０２回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] Association of perioperative blood transfusion with oncological outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. (2014)
  • Author(s): Rieken M, Schubert T, Xylinas E, Kluth L, Roupret M, Trinh QD, Lee RK, Awamlh AI, Fajkovic H, Novara G, Margulis V, Lotan Y, Martinez-Salamanca JI, Matsumoto K, Seitz C, Remz M, Karakiewicz PI, Scherr DS, Briganti A, Bachmann A, Shariat SF.
  • Organizer: 29th Annual European Association of Urology Congress
  • Place of Presentation: Stockholm(スウェーデン)
  • Year and Date: 2014-04-11 – 2014-04-16
• [Presentation] Increased expression of serum uroplakin III is associated with the detection and pathological features of aggressive bladder cancer. (2014)
  • Author(s): Tsumura H, Matsumoto K, Matsumoto T, Ikeda M, Satoh T, Yoshida K, Sato Y, Iwamura M.
  • Organizer: 29th Annual European Association of Urology Congress
  • Place of Presentation: Stockholm(スウェーデン)
  • Year and Date: 2014-04-11 – 2014-04-16
• [Presentation] Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of over 8000 patients. (2014)
  • Author(s): Kluth LA, Rieken M, Xylinas E, Kent M, Rink M, Roupret M, Sharifi N, Jamzadeh A, Kassouf W, Kaushik D, Boorjian SA, Rhogmann F, Noldus J, Masson-Lecomte A, Vordos D, Ikeda M, Matsumoto K, Hagiwara M, Kikuchi E, Fradet Y, Rendon R, Fairey A, Lotan Y, Bachmann A, Zerbib M, Fisch M, Scherr DS, Vickers A, Shariat SF.
  • Organizer: 29th Annual European Association of Urology Congress
  • Place of Presentation: Stockholm(スウェーデン)
  • Year and Date: 2014-04-11 – 2014-04-16
• [Book] Bladder Cancer: Risk Factors, Emerging Treatment Strategies and Challenges. (2014)
  • Author(s): Matsumoto K, Ikeda M, Hirayama T, Fujita T, Iwamura M.Samantha Haggerty,etc.
  • Total Pages: 174(145-160)
  • Publisher: Nova Science Publishers, Inc,
• [Book] Hematuria: Etiology, Management and Long-Term Prognosis. (2014)
  • Author(s): Hirayama T, Matsumoto K, Nishi M, Fujita T, Iwamura M,Nikhil Vasdev and G.Boustead,etc.
  • Total Pages: 204(77-83)
  • Publisher: Nova Science Publishers, Inc,
• [Patent(Industrial Property Rights)] 膀胱癌の診断 (2015)
  • Inventor(s): 松本和将、大草 洋、馬場志郎、小寺義男、前田忠計
  • Industrial Property Rights Holder: 松本和将、大草 洋、馬場志郎、小寺義男、前田忠計
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願 2015-020750
  • Filing Date: 2015-02-20