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2018 Fiscal Year Research-status Report

Tumor targeting using boron neutron capture therapy

Research Project

Project/Area Number 17K11119
Research InstitutionHirosaki University

Principal Investigator

畠山 真吾  弘前大学, 医学部附属病院, 講師 (10400136)

Co-Investigator(Kenkyū-buntansha) 米山 徹  弘前大学, 医学研究科, 助教 (50587649)
石山 新太郎  弘前大学, 理工学研究科, 教授 (60355021)
飛澤 悠葵  弘前大学, 医学研究科, 助教 (70623768)
大山 力  弘前大学, 医学研究科, 教授 (80282135)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywordsがん特異的中性子治療 / ペプチド
Outline of Annual Research Achievements

2018年度の成果として以下の結果を得た。①ホウ素10核種(10B-IF7の合成:IF7ペプチドと10B原子の合成を行い新規10B-IF7の開発を試みた。またホウ素化合物(ボロン薬剤)には10B原子、ボロカプテイト (Borocaptate Sodium:BSH)、ボロンフェニルアラニン(ホウ素+フェニルアラニン:BPA)の3種類がある。10B原子そのものはがん特異性が低いため、臨床応用には10B原子を籠状に配列したBSHやフェニルアラニンの取り込みを利用したBPAが用いられてきた。また、IF7ペプチドは末端にシステインが付加されており、様々な分子と化学結合可能である。過去の検討により、IF7は架橋剤(クロスリンカー)を用いて各種薬剤と結合を試みた。その結果、本研究でも同様の手法を用いIF7と10B原子を結合させ、10B-IF7を合成することに成功し、2種(10BSH-IF7、10BPA-IF7)を開発した。②我々の開発したIF7ペプチドはがん特異性が高いため、がん特異性が低い10B原子や10BSHをIF7ペプチドと結合させ、がん特異性を向上させることが可能であると仮定し、この2種のホウ素-IF7を用いてマウス固形腫瘍モデルに投与し、ホウ素集積を検討した。膀胱癌細胞株MBT2をマウスの皮下に移植し、1x1㎝程度の大きさになったところでBPA単独、10BSH-IF7、10BPA-IF7を尾静脈注射にて投与した。初回実験では既存の有効ホウ素投与量(BPA単独)に調整したところ、IF7の投与量が過剰となり、投与後に死亡してしまったため、投与法を腹腔内投与とした。その後、5分、10分、20分、40分で臓器を摘出しボロン薬剤の集積を検討した。その結果、腫瘍に特異的に集積する傾向が確認され、マウスでの治療効果を検討中である

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

平成29年度の目標は10B-IF7の合成であり、これは合成に成功した。IF7は架橋剤(クロスリンカー)を用いて各種薬剤と結合を試みることにより、本研究でも同様の手法を用いIF7と10B原子を結合させ、10B-IF7を合成することに成功した。その結果、10BSH-IF7と10BPA-IF7の2種の新規薬剤を開発することができた。平成30年度はマウスでの抗腫瘍効果を確認することであった。京都大学の原子炉にて中性子照射実験を2回行ったが、効果にばらつきがあり、現在安定的な効果を検出できる実験系を検討中である。徐々に成果が出ているが、原子炉の使用に制限があり思うように実験が組めないのが難点である。そのため、おおむね順調に進展していると判断できるが、進捗は遅く、やや遅れていると判断される。

Strategy for Future Research Activity

今後はがんモデルマウスによる10B-IF7の抗腫瘍効果を確認するための条件設定を行い、京都大学原子炉実験所にて、照射時間の調整を検討する必要がある。また10B-IF7の体内動態を調べるため、Invivo imagingも実験可能か協議中である。また種々の癌種への応用効果を検討するため、前立腺癌、膀胱癌、腎癌など泌尿器固形腫瘍の皮下移植モデル、同所移植モデルも作成が必要である。よって今後も更なる検討を継続する。

Causes of Carryover

実験消耗品の一部を次年度に見送ることにしたため、差額が生じた。次年度の実験消耗品で使用する予定である。

  • Research Products

    (32 results)

All 2018

All Journal Article (25 results) (of which Int'l Joint Research: 25 results,  Peer Reviewed: 24 results) Presentation (7 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Impact of nutritional status on the prognosis of patients with metastatic hormone-na?ve prostate cancer: a multicenter retrospective cohort study in Japan2018

    • Author(s)
      Okamoto Teppei、Hatakeyama Shingo、Narita Shintaro、Takahashi Masahiro、Sakurai Toshihiko、Kawamura Sadafumi、Hoshi Senji、Ishida Masanori、Kawaguchi Toshiaki、Ishidoya Shigeto、Shimoda Jiro、Sato Hiromi、Mitsuzuka Koji、Tochigi Tatsuo、Tsuchiya Norihiko、Arai Yoichi、Habuchi Tomonori、Ohyama Chikara
    • Journal Title

      World Journal of Urology

      Volume: 99 Pages: 000-0001

    • DOI

      10.1007/s00345-018-2590-2

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Postoperative weight loss followed by radical cystectomy predicts poor prognosis in patients with muscle-invasive bladder cancer2018

    • Author(s)
      Okita Kazutaka、Hatakeyama Shingo、Fujita Naoki、Konishi Sakae、Yamamoto Hayato、Imai Atsushi、Yoneyama Takahiro、Hashimoto Yasuhiro、Ito Hiroyuki、Yoshikawa Kazuaki、Koie Takuya、Ohyama Chikara
    • Journal Title

      Medical Oncology

      Volume: 36 Pages: 0001

    • DOI

      10.1007/s12032-018-1232-2

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparison of axitinib and sunitinib as first-line therapies for metastatic renal cell carcinoma: a real-world multicenter analysis2018

    • Author(s)
      Konishi Sakae、Hatakeyama Shingo、Tanaka Toshiaki、Ikehata Yoshinori、Tanaka Toshikazu、Fujita Naoki、Ishibashi Yusuke、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Yoshikawa Kazuaki、Kawaguchi Toshiaki、Masumori Naoya、Kitamura Hiroshi、Ohyama Chikara
    • Journal Title

      Medical Oncology

      Volume: 36 Pages: 6

    • DOI

      10.1007/s12032-018-1231-3

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical impact of glomerular basement membrane thickness on post‐donation renal function in living donors2018

    • Author(s)
      Kubota Yuka、Hatakeyama Shingo、Narita Ikuyo、Shimada Michiko、Hashimoto Yasuhiro、Ohyama Chikara
    • Journal Title

      International Journal of Urology

      Volume: 26 Pages: 309~311

    • DOI

      10.1111/iju.13850

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report2018

    • Author(s)
      Hamano I.、Hatakeyama S.、Yamamoto H.、Fujita T.、Murakami R.、Shimada M.、Imai A.、Yoneyama T.、Yoneyama T.、Hashimoto Y.、Koie T.、Narumi S.、Saitoh H.、Suzuki T.、Tomita H.、Ohyama C.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Pages: 2553~2557

    • DOI

      10.1016/j.transproceed.2018.02.182

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neoadjuvant chemohormonal therapy followed by robot-assisted and minimum incision endoscopic radical prostatectomy in patients with high-risk prostate cancer: comparison of perioperative and oncological outcomes at single institution2018

    • Author(s)
      Fujita Naoki、Koie Takuya、Hashimoto Yasuhiro、Narita Takuma、Tobisawa Yuki、Tanaka Toshikazu、Noro Daisuke、Oikawa Masaaki、Hagiwara Kazuhisa、Yoneyama Tohru、Imai Atsushi、Yamamoto Hayato、Hatakeyama Shingo、Yoneyama Takahiro、Ohyama Chikara
    • Journal Title

      International Urology and Nephrology

      Volume: 50 Pages: 1999~2005

    • DOI

      10.1007/s11255-018-1985-8

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan2018

    • Author(s)
      Matsumoto Teppei、Hatakeyama Shingo、Imai Atsushi、Tanaka Toshikazu、Hagiwara Kazuhisa、Konishi Sakae、Okita Kazutaka、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Nakaji Shigeyuki、Ohyama Chikara
    • Journal Title

      BJU International

      Volume: 123 Pages: 877~884

    • DOI

      10.1111/bju.14535

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Robotic cross-folded U-configuration intracorporeal ileal neobladder for muscle-invasive bladder cancer: Initial experience and functional outcomes2018

    • Author(s)
      Koie Takuya、Ohyama Chikara、Yoneyama Takahiro、Nagasaka Hirotaka、Yamamoto Hayato、Imai Atsushi、Hatakeyama Shingo、Hashimoto Yasuhiro
    • Journal Title

      The International Journal of Medical Robotics and Computer Assisted Surgery

      Volume: 14 Pages: e1955~e1955

    • DOI

      10.1002/rcs.1955

    • Int'l Joint Research
  • [Journal Article] Low serum butyrylcholinesterase is independently related to low fetuin-A in patients on hemodialysis: a cross-sectional study2018

    • Author(s)
      Okamoto Teppei、Tsutaya Chikako、Hatakeyama Shingo、Konishi Sakae、Okita Kazutaka、Tanaka Yoshimi、Imanishi Kengo、Takashima Tooru、Saitoh Fumitada、Suzuki Tadashi、Ohyama Chikara
    • Journal Title

      International Urology and Nephrology

      Volume: 50 Pages: 1713~1720

    • DOI

      10.1007/s11255-018-1957-z

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Proton pump inhibitor as an independent factor of progression of abdominal aortic calcification in patients on maintenance hemodialysis2018

    • Author(s)
      Okamoto Teppei、Hatakeyama Shingo、Hosogoe Shogo、Tanaka Yoshimi、Imanishi Kengo、Takashima Toru、Saitoh Fumitada、Suzuki Tadashi、Ohyama Chikara
    • Journal Title

      PLOS ONE

      Volume: 13 Pages: e0199160

    • DOI

      10.1371/journal.pone.0199160

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differences in semen characteristics between patients with testicular cancer and other malignancies using various cut-off values2018

    • Author(s)
      Hamano Itsuto、Hatakeyama Shingo、Nakamura Rika、Fukuhara Rie、Noro Daisuke、Tanaka Toshikazu、Yoneyama Tohru、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Yokoyama Yoshihito、Ohyama Chikara
    • Journal Title

      International Journal of Urology

      Volume: 25 Pages: 817~824

    • DOI

      10.1111/iju.13732

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma2018

    • Author(s)
      Momota Masaki、Hatakeyama Shingo、Yamamoto Hayato、Iwamura Hiromichi、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Iwabuchi Ikuya、Ogasawara Masaru、Kawaguchi Toshiaki、Ohyama Chikara
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 23047-23057

    • DOI

      10.18632/oncotarget.25198

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Asymptomatic recurrence detection and cost-effectiveness in urothelial carcinoma2018

    • Author(s)
      Iwamura Hiromichi、Hatakeyama Shingo、Sato Makoto、Ohyama Chikara
    • Journal Title

      Medical Oncology

      Volume: 35 Pages: 94

    • DOI

      10.1007/s12032-018-1152-1

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sleep Disturbance Has a Higher Impact on General and Mental Quality of Life Reduction than Nocturia: Results from the Community Health Survey in Japan2018

    • Author(s)
      Kido Koichi、Hatakeyama Shingo、Imai Atsushi、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Nakaji Shigeyuki、Ohyama Chikara
    • Journal Title

      European Urology Focus

      Volume: 99 Pages: 0001

    • DOI

      10.1016/j.euf.2018.04.017

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical implication of a quantitative frailty assessment tool for prognosis in patients with urological cancers2018

    • Author(s)
      Soma Osamu、Hatakeyama Shingo、Okamoto Teppei、Fujita Naoki、Matsumoto Teppei、Tobisawa Yuki、Yoneyama Tohru、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Nakaji Shigeyuki、Ohyama Chikara
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 0001

    • DOI

      10.18632/oncotarget.24712

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Partial Cystectomy of Paraganglioma of the Urinary Bladder Before Living Kidney Transplantation: Case Report2018

    • Author(s)
      Kido K.、Hatakeyama S.、Hamano I.、Yamamoto H.、Imai A.、Yoneyama T.、Hashimoto Y.、Koie T.、Fujita T.、Murakami R.、Tomita H.、Suzuki T.、Narumi S.、Ohyama C.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Pages: 898~901

    • DOI

      10.1016/j.transproceed.2018.01.015

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Butyrylcholinesterase level as an independent factor of erythropoiesis-stimulating agent resistance in patients on maintenance hemodialysis: a single-center cross-sectional study2018

    • Author(s)
      Okamoto Teppei、Hatakeyama Shingo、Tanaka Yoshimi、Imanishi Kengo、Takashima Tooru、Saitoh Fumitada、Koie Takuya、Suzuki Tadashi、Ohyama Chikara
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 22 Pages: 1174~1181

    • DOI

      10.1007/s10157-018-1569-z

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Case of Fibrous Pseudotumor in the Scrotum: Challenge for Diagnosis and Testicular Preservation2018

    • Author(s)
      Kodama Hirotake、Hatakeyama Shingo、Matsumoto Teppei、Tanaka Toshikazu、Horiguchi Hirotaka、Kubota Yuka、Yamamoto Hayato、Imai Atsushi、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Ohyama Chikara
    • Journal Title

      Case Reports in Urology

      Volume: 2018 Pages: 1~4

    • DOI

      10.1155/2018/6904827

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The relationship between poor nutritional status and progression of aortic calcification in patients on maintenance hemodialysis2018

    • Author(s)
      Okamoto Teppei、Hatakeyama Shingo、Kodama Hirotake、Horiguchi Hirotaka、Kubota Yuka、Kido Koichi、Momota Masaki、Hosogoe Shogo、Tanaka Yoshimi、Takashima Tooru、Saitoh Fumitada、Suzuki Tadashi、Ohyama Chikara
    • Journal Title

      BMC Nephrology

      Volume: 19 Pages: 0001

    • DOI

      10.1186/s12882-018-0872-y

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma2018

    • Author(s)
      Momota Masaki、Hatakeyama Shingo、Tokui Noriko、Sato Tendo、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Narita Satoshi、Kawaguchi Toshiaki、Ohyama Chikara
    • Journal Title

      European Urology Focus

      Volume: 99 Pages: 001

    • DOI

      10.1016/j.euf.2018.03.003

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detecting asymptomatic recurrence after radical nephroureterectomy contributes to better prognosis in patients with upper urinary tract urothelial carcinoma2018

    • Author(s)
      Horiguchi Hirotaka、Hatakeyama Shingo、Anan Go、Kubota Yuka、Kodama Hirotake、Momota Masaki、Kido Koichi、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Ito Hiroyuki、Yoshikawa Kazuaki、Kawaguchi Toshiaki、Sato Makoto、Ohyama Chikara
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 8746

    • DOI

      10.18632/oncotarget.23982

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of bacillus Calmette?Gu?rin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy2018

    • Author(s)
      Horiguchi Hirotaka、Yoneyama Takahiro、Hatakeyama Shingo、Tokui Noriko、Sato Tendo、Fujita Naoki、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Hashimoto Yasuhiro、Koie Takuya、Yoshikawa Kazuaki、Narita Satoshi、Kawaguchi Toshiaki、Ohyama Chikara
    • Journal Title

      Medical Oncology

      Volume: 35 Pages: 41

    • DOI

      10.1007/s12032-018-1102-y

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma2018

    • Author(s)
      Kido Koichi、Hatakeyama Shingo、Fujita Naoki、Yamamoto Hayato、Tobisawa Yuki、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Iwabuchi Ikuya、Ogasawara Masaru、Kawaguchi Toshiaki、Ohyama Chikara
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 23 Pages: 726~733

    • DOI

      10.1007/s10147-018-1248-9

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Onco-testicular sperm extraction (Onco-TESE) from a single testis with metachronous bilateral testicular cancer: a case report2018

    • Author(s)
      Hamano Itsuto、Hatakeyama Shingo、Nakamura Rika、Fukuhara Rie、Noro Daisuke、Seino Hiroko、Yoneyama Takahiro、Hashimoto Yasuhiro、Koie Takuya、Yokoyama Yoshihito、Ohyama Chikara
    • Journal Title

      Basic and Clinical Andrology

      Volume: 28 Pages: 0001

    • DOI

      10.1186/s12610-018-0066-2

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Slow Progression of Aortic Calcification Is a Potential Benefit of Pre-emptive Kidney Transplantation2018

    • Author(s)
      Mursawa H.、Hatakeyama S.、Yamamoto H.、Tanaka Y.、Soma O.、Matsumoto T.、Yoneyama T.、Hashimoto Y.、Koie T.、Fujita T.、Murakami R.、Saitoh H.、Suzuki T.、Narumi S.、Ohyama C.
    • Journal Title

      Transplantation Proceedings

      Volume: 50 Pages: 145~149

    • DOI

      10.1016/j.transproceed.2017.12.011

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Clinical impact of glomerular basement membrane thickness on donor renal function after kidney donation2018

    • Author(s)
      Hatakeyama S, Yoneyama T, Kodama H, Kusaka A, Hosogoe S, Tokui N, Yamamoto H, Yoneyama T, Hashimoto Y, Koie T, Ohyma C
    • Organizer
      米国泌尿器科会議)2018年5月18-21日 サンフランシスコ
    • Int'l Joint Research
  • [Presentation] Diagnostic potential of aberrant N-Glycosylation of serum immunoglobulins in patients with urothelial carcinoma2018

    • Author(s)
      Hatakeyama S, Yoneyama T, Ohyama C
    • Organizer
      URS 2018 IN KOREA 2018.10.1-2.  韓国ソウル
    • Int'l Joint Research
  • [Presentation] The relationship between preoperative stage 3B chronic kidney disease and post-surgical oncological outcomes in patients with urothelial carcinoma2018

    • Author(s)
      Hatakeyama S, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
    • Organizer
      ESMO ASIA 2018年11月22-25日 シンガポール
    • Int'l Joint Research
  • [Presentation] Does neoadjuvant chemotherapy promote chemoresistance after recurrence in patients with muscle-invasive bladder cancer?2018

    • Author(s)
      Hatakeyama S, Kodama H, Konishi S, Okita K, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
    • Organizer
      ESMO ASIA 2018年11月22-25日 シンガポール
    • Int'l Joint Research
  • [Presentation] The gap of frailty value from a community-dwelling population predict oncological outcomes in patients with urological cancers.2018

    • Author(s)
      Hatakeyama S, Konishi S, Okita K, Soma O, Matsumoto T, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
    • Organizer
      ESMO ASIA 2018年11月22-25日 シンガポール
    • Int'l Joint Research
  • [Presentation] Impact of frailty on treatment modality selection in patients with muscle-invasive bladder cancer: Radical cystectomy vs bladder preservation therapy2018

    • Author(s)
      Hatakeyama S, Soma O, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Ohyama C
    • Organizer
      EAU 2019 第34回欧州泌尿器学会議 2019年3月15-19日 スペイン(バルセロナ)
  • [Presentation] Development and validation of the prediction nomogram for a stone episode2018

    • Author(s)
      Hatakeyama S, Imai A, Hamano I, Tanaka T, Yoneyama T, Yamamoto H, Yoneyama T, Hashimoto Y, Nakaji S, Ohyama C
    • Organizer
      EAU 2019 第34回欧州泌尿器学会議 2019年3月15-19日 スペイン(バルセロナ)

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Published: 2019-12-27  

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