癌特異的分子アネキシンを標的とした泌尿器癌化学療法の開発

2014 Fiscal Year Annual Research Report

• Project/Area Number: 23791737
• Research Institution: Hirosaki University
• Principal Investigator: 畠山 真吾 弘前大学, 医学部附属病院, 講師 (10400136)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 癌特異的化学療法 / ペプチド

Outline of Annual Research Achievements

癌化学療法は、副作用の問題が常に課題としてあげられる。癌患者の増加とともに、高効果・低副作用な抗癌剤の開発が求められている。2004年のNatureに固形腫瘍の癌特異的分子としてアネキシンが報告された。我々はアネキシン結合ぺプチドを同定した。ペプチドの利点は容易に化学合成可能で、各種抗癌剤との組み合わせも可能である点、大量合成によりコスト削減が期待でき、抗体医薬品のように高価にはならないと考えられる。本研究では、現在臨床応用されている抗癌剤にペプチドを組み合わせ、高効果かつ低副作用な癌特異的抗癌剤の開発を目的とした。癌特異的化学療法の基礎となる抗癌剤の合成・精製実験を行い、タキサン系薬剤であるドセタキセルとの合成に成功し、動物実験モデルを作成し抗がん剤として有効かどうかの検討を行った。抗腫瘍効果は得られる傾向が得られたが、抗がん剤として使用する場合の容量設定が今後の課題として考えられた。

Research Products

• [Journal Article] Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy. (2014)
  • Author(s): Koie T, Ohyama C, Mikami J, Iwamura H, Fujita N, Sato T, Kojima Y, Fukushi K, Yamamoto H, Imai A, Hatakeyama S, Yoneyama T, Hashimoto Y, Kitayama M, Hirota K.
  • Journal Title: ScientificWorldJournal. Volume: 2014 Pages: 948305
  • DOI: 10.1155/2014/948305.
  • Peer Reviewed / Open Access
• [Journal Article] Differences in the recurrence pattern after neoadjuvant chemotherapy compared to surgery alone in patients with muscle-invasive bladder cancer. (2014)
  • Author(s): Koie T, Ohyama C, Yamamoto H, Imai A, Hatakeyama S, Yoneyama T, Hashimoto Y, Yoneyama T, Tobisawa Y.
  • Journal Title: Med Oncol. Volume: 32 Pages: 421
  • DOI: 10.1007/s12032-014-0421-x
  • Peer Reviewed
• [Journal Article] Serum tri- and tetra-antennary N-glycan is a potential predictive biomarker for castration-resistant prostate cancer. (2014)
  • Author(s): Ishibashi Y, Tobisawa Y, Hatakeyama S, Ohashi T, Tanaka M, Narita S, Koie T, Habuchi T, Nishimura S, Ohyama C, Yoneyama T.
  • Journal Title: Prostate. Volume: 74 Pages: 1521-1529
  • DOI: 10.1002/pros.22869.
  • Peer Reviewed
• [Journal Article] Tubulocystic renal cell carcinoma in the left kidney: a case report. (2014)
  • Author(s): Ishibashi Y, Koie T, Fujita N, Satoh T, Mikami J, Hatakeyama S, Ohyama C, Tobisawa Y, Yoneyama T.
  • Journal Title: J Med Case Rep. Volume: 8 Pages: 265
  • DOI: 10.1186/1752-1947-8-265.
  • Peer Reviewed
• [Journal Article] Significance of preoperative butyrylcholinesterase as an independent predictor of survival in patients with muscle-invasive bladder cancer treated with radical cystectomy. (2014)
  • Author(s): Koie T, Ohyama C, Yamamoto H, Hatakeyama S, Imai A, Yoneyama T, Hashimoto Y, Kitayam M, Hirota K.
  • Journal Title: Urol Oncol. Volume: 32 Pages: 820-825
  • DOI: 10.1016/j.urolonc.2014.03.010.
  • Peer Reviewed
• [Journal Article] arboplatin-based combination chemotherapy for elderly patients with advanced bladder cancer. (2014)
  • Author(s): Yoneyama T, Tobisawa Y, Yoneyama T, Yamamoto H, Imai A, Hatakeyama S, Hashimoto Y, Koie T, Ohyama C.
  • Journal Title: Int J Clin Oncol. Volume: 20 Pages: 369-374
  • DOI: 10.1007/s10147-014-0706-2.
  • Peer Reviewed
• [Journal Article] Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer. (2014)
  • Author(s): Yoneyama T, Ohyama C, Hatakeyama S, Narita S, Habuchi T, Koie T, Mori K, Hidari KI, Yamaguchi M, Suzuki T, Tobisawa Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 448 Pages: 390-396
  • DOI: 10.1016/j.bbrc.2014.04.107.
  • Peer Reviewed
• [Journal Article] Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis. (2014)
  • Author(s): Sutoh Yoneyama M, Hatakeyama S, Habuchi T, Inoue T, Nakamura T, Funyu T, Wiche G,Ohyama C, Tsuboi S.
  • Journal Title: Eur J Cell Biol. Volume: 93 Pages: 157-169
  • DOI: 10.1016/j.ejcb.2014.03.002.
  • Peer Reviewed
• [Journal Article] Reassessment of prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma: analysis in terms of proposed pT3 subclassification systems. (2014)
  • Author(s): Park J, Habuchi T, Arai Y, Ohyama C, Inoue T, Hatakeyama S, Jeon SS, Kwon GY, Kwak C, Moon KC, Kim CS, Ahn H.
  • Journal Title: J Urol. Volume: 192 Pages: 1064-1071
  • DOI: 10.1016/j.juro.2014.04.001.1064-1071
  • Peer Reviewed
• [Journal Article] Neoadjuvant gemcitabine and carboplatin followed by immediate cystectomy may be associated with a survival benefit in patients with clinical T2 bladder cancer. (2014)
  • Author(s): Koie T, Ohyama C, Yamamoto H, Imai A, Hatakeyama S, Yoneyama T, Hashimoto Y, Yoneyama T, Tobisawa Y.
  • Journal Title: Med Oncol. Volume: 31 Pages: 949
  • DOI: 10.1007/s12032-014-0949-9.
  • Peer Reviewed
• [Journal Article] Invadopodia are essential in transurothelial invasion during the muscle invasion of bladder cancer cells. (2014)
  • Author(s): Imanishi K, Yoneyama MS, Hatakeyama S, Yamamoto H, Koie T, Saitoh H, Yamaya K, Funyu T, Nakamura T, Ohyama C, Tsuboi S.
  • Journal Title: Mol Med Rep. Volume: 9 Pages: 2159-2165
  • DOI: 10.3892/mmr.2014.2113.
  • Peer Reviewed
• [Journal Article] Extravasation during bladder cancer metastasis requires cortactin‑mediated invadopodia formation. (2014)
  • Author(s): Tokui N, Yoneyama MS, Hatakeyama S, Yamamoto H, Koie T, Saitoh H, Yamaya K, Funyu T, Nakamura T, Ohyama C, Tsuboi S.
  • Journal Title: Mol Med Rep. Volume: 9 Pages: 1142-1146
  • DOI: 10.3892/mmr.2014.1965.
  • Peer Reviewed
• [Presentation] 生体腎移植ドナー腎採取術3 術式間の比較検討 (2014)
  • Author(s): 畠山真吾，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第28回日本泌尿器内視鏡学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-26 – 2014-11-28
• [Presentation] ミニマム創手術とダビンチ手術のメリット・デメリット：前立腺全摘除術、膀胱全摘除術の考察． (2014)
  • Author(s): 畠山真吾，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第79回日本泌尿器科学会東部総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-10-12 – 2014-10-14
• [Presentation] Significance of serum N-glycan alteration associated with antibody mediated rejection in renal transplant recipients detected by High-throughput glycan analysis (2014)
  • Author(s): Hatakeyama S, Saito M, Inoue T, Tobisawa Y, Yoneyama T, Tuchiya N, Satoh S, Habuchi T, Ohyama C
  • Organizer: Hirosaki International Symposium on Transplant 2014
  • Place of Presentation: Hirosaki
  • Year and Date: 2014-08-31 – 2014-08-31
• [Presentation] A switch from conventional twice-daily tacrolimus to once-daily tacrolimus extended-release in stable kidney transplant recipients. (2014)
  • Author(s): Hatakeyama S, Fujita T, Yoneyama T, Yoneyama T, Koie T, Hashimoto Y, Saitoh H, Funyu T, Narumi S, Ohyama C
  • Organizer: Hirosaki International Symposium on Transplant 2014
  • Place of Presentation: Hirosaki
  • Year and Date: 2014-08-31 – 2014-08-31
• [Presentation] Outcome comparison of abo-incompatible kidney transplantation with low dose rituximab and abo-compatible kidney transplantation: A single-center experience. (2014)
  • Author(s): Hatakeyama S, Fujita T, Murakami R, Suzuki Y, Sugiyama N, Yamamoto H, Okamoto A, Imai A, Tobisawa Y, Yoneyama T, Mori K, Yoneyama T, Koie T, Hashimoto Y, Narumi S, Ohyama C
  • Organizer: Hirosaki International Symposium on Transplant 2014
  • Place of Presentation: Hirosaki
  • Year and Date: 2014-08-31 – 2014-08-31
• [Presentation] Post-transplant renal function and cardiovascular events are closely associated with the aortic calcification index (ACI) in renal transplant recipients. (2014)
  • Author(s): Hatakeyama S, Imanishi K, Yamamoto H, Okamoto A, Imai A, Yoneyama T, Hashimoto Y, Koie T, Fujita T, Murakami R, Saitoh H, Funyu T, Narumi S, Ohyama C
  • Organizer: Hirosaki International Symposium on Transplant 2014
  • Place of Presentation: Hirosaki
  • Year and Date: 2014-08-31 – 2014-08-31
• [Presentation] BK virus-associated urothelial carcinoma of a ureter graft in a renal transplant recipient : a case report. (2014)
  • Author(s): Oikawa M, Hatakeyama S, Fujita T, Murakami R, Hagiwara K, Narita T, Noro D, Tanaka T, Tanaka Y, Tobisawa Y, Yoneyama T, Yoneyama Y, Hashimoto Y, Koie T, Narumi S, Ohyama C
  • Organizer: Hirosaki International Symposium on Transplant 2014
  • Place of Presentation: Hirosaki
  • Year and Date: 2014-08-31 – 2014-08-31
• [Presentation] 透析腎癌スクリーニング検査の有用性と限界についての検討 (2014)
  • Author(s): 畠山真吾，岡本亜希子，米山高弘，橋本安弘，大山 力，齋藤久夫，舟生富寿
  • Organizer: 第41回東北腎不全研究会
  • Place of Presentation: 秋田
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] 生体腎移植ドナー術後の腎機能についての検討． (2014)
  • Author(s): 畠山真吾，藤田 雄，村上礼一，山本勇人，今井 篤，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第30回腎移植・血管外科研究会
  • Place of Presentation: 那覇
  • Year and Date: 2014-06-27 – 2014-06-28
• [Presentation] 透析腎癌における画像診断の限界についての検討 (2014)
  • Author(s): 畠山真吾，岡本亜希子，工藤茂将，米山高弘，橋本安弘，斎藤久夫，大山 力，舟生富寿
  • Organizer: 第59回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-06-12 – 2014-06-15
• [Presentation] Post-transplant renal function is closely correlated with aortic calcification index (ACI) progression rate in renal transplant recipients. (2014)
  • Author(s): Hatakeyama S, Yoneyama T, Koie T, Fujita T, Murakami R, Saito H, Narumi S, Funyu T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Prognostic benefit of surgical management in RCC patients with thrombus extending to the renal vein and inferior vena cava: a propensity score matched analysis. (2014)
  • Author(s): Hatakeyama S, Yoneyama T, Yamamoto H, Imai A, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Safety of heparin bridging therapy for transrectal ultrasound-guided prostate biopsy (TRUS-Pb) in patients requiring temporary discontinuation of warfarin. (2014)
  • Author(s): Hamano I, Hatakeyama S, Kusaka A, Imanishi K, Tokui N, Okamoto T, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] BMI38の症例に対して行ったロボット支援下膵体尾部切除+腎切除の経験． (2014)
  • Author(s): 畠山真吾，山本勇人，岡本亜希子，今井 篤，米山高弘，橋本安弘，古家琢也，石戸圭之輔，袴田健一，大山 力
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 膀胱全摘か温存療法か？高齢者の筋層浸潤膀胱癌についての検討 (2014)
  • Author(s): 畠山真吾，杉山尚樹，鈴木裕一朗，山本勇人，今井 篤，岡本亜希子，米山高弘，橋本安弘，古家琢也，大山 力
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 尿酸成分を有する結石は慢性腎臓病(CKD)のリスク因子である (2014)
  • Author(s): 畠山真吾，寺山百合子，齋藤文匡，齋藤久夫，橋本安弘，古家琢也，舟生富壽，大山 力
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Radiologic response predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy. (2014)
  • Author(s): Hatakeyama S, Yamamoto H, Okamoto A, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会
  • Place of Presentation: Stockholm
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Presence of transient hydronephrosis immediately after surgery has limited influence on renal function at one year after ileal neobladder construction. (2014)
  • Author(s): Narita T, Hatakeyama S, Koie T, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会
  • Place of Presentation: Stockholm
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Clinical and pathological characteristics of the patients in spite of positive surgical margins who were free from biochemical recurrence after radical prostatectomy (2014)
  • Author(s): Hatakeyama S, Mitsuzuka K, Narita S, Koie T, Yoneyama T, Hashimoto Y, Tsuchiya N, Kawamura S, Habuchi T, Arai Y, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会
  • Place of Presentation: Stockholm
  • Year and Date: 2014-04-11 – 2014-04-11