Development of a novel enzyme-targeting radiosensitizer (New KORTUC) using a gelatin-based hydrogel instead of a siduim hyaluronate

• Project/Area Number: 25461916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kochi University
• Principal Investigator: OGAWA YASUHIRO 高知大学, その他の部局等, 名誉教授 (90152397)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 放射線増感剤 / KORTUC / 過酸化水素 / ヒアルロン酸 / ハイドロゲル / 架橋ゼラチン / 腫瘍低酸素 / 放射線抵抗性 / マウス / SCCVII

Outline of Final Research Achievements

We recently developed KORTUC as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect.

Research Products

• [Journal Article] Development of a novel enzyme-targeting radiosensitizer (New KORTUC) using a gelatin-based hydrogel instead of a sodium hyalutronate (2016)
  • Author(s): Morita-Tokuhiro S, Ogawa Y, Yokota N, Tsuzuki A, Oda H, Ishida N, Aoyama N, Nishioka A
  • Journal Title: Cancers Volume: 8 Issue: 1 Pages: 10-10
  • DOI: 10.3390/cancers8010010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Computed tomography demonstration of the production and distribution of oxygen gas following intratumoral injection of a new radiosensitizer (KORTUC) for patients with breast cancer - is intratumoral injection not an ideal approach to solve the major problem of tumor hypoxia in radiotherapy? (2016)
  • Author(s): Hayashi N, Ogawa Y, Kubota K, Okino K, Akima R, Morita-Tokuhiro S, Tsuzuki A, Yaogawa S, Nishioka A, Miyamura M
  • Journal Title: Cancers Volume: 8 Issue: 4 Pages: 43-43
  • DOI: 10.3390/cancers8040043
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serail assessment of therapeutic response to a new radiosensitization treatment, kochi Oxydol-radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), in patients with stage I/II breast cancer using breast contrast-enhanced magnetic resonance imaging (2016)
  • Author(s): Yaogawa S, Ogawa Y, Morita-Tokuhiro S, Tsuzuki A, Akima R, Itoh K, Morio K, Yasunami H, Onogawa M, Kariya S, Nogami M, Nishioka A, Miyamura M
  • Journal Title: cancers Volume: 8 Issue: 1 Pages: 1-11
  • DOI: 10.3390/cancers8010001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Raradigm shift in radiation biology/radiation oncology - Exploitation of the "H2O2 effect" for radiotherapy using low-LET (linear energy transfer) radiation such as x-rays and high-energy electrons (2016)
  • Author(s): Ogawa Y
  • Journal Title: Cancers Volume: 8 Issue: 3 Pages: 28-28
  • DOI: 10.3390/cancers8030028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic response to a novel enzyme-targeting radiosensitization treatment (Kochi Oxydol-Radiation Therapy for Unresedctable carcinomas) in patients with recurrent breast cancer (2016)
  • Author(s): Aoyama N, Ogawa Y, Yasuoka M, Takahashi M, Iwasa H, Miyatake K, Yamanishi T, Hamada N, Tamura T, Nishioka A, Yamagami T
  • Journal Title: Oncology Letters Volume: 11 Issue: 1 Pages: 1-6
  • DOI: 10.3892/ol.2016.4589
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Non-surgical breast-conserving treatment (KORTUC-BCT) using a new radiosensitization method (KORTUC II) for patients with stage I or II breast cancer (2015)
  • Author(s): Ogawa Y, Kubota K, Aoyama N, Yamanishi T, Kariya S, Hamada N, Nogami M, Nishioka A, Onogawa M, Miyamura M
  • Journal Title: Cancers Volume: 7 Issue: 4 Pages: 2277-89
  • DOI: 10.3390/cancers7040891
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Safety and efficacy of image-guided enzyme-targeting radiosensitization and intraoperative radiotherapy for locally advanced unresectable pancreatic cancer (2014)
  • Author(s): Nishioka A, Ogawa Y, Miyatake K, Tadokoro M, Nogami M, Hamada N, Kubota K, Kariya S, Kohsaki T, Saibara T, Okabayashi T, Hanazaki K
  • Journal Title: Oncology Letters Volume: 8 Pages: 404-408
  • Peer Reviewed
• [Journal Article] 肝細胞癌の左鎖骨上かリンパ節転移 (2014)
  • Author(s): 小川恭弘、山西伴明、青山信隆、野上宗伸、久保田 敬
  • Journal Title: 臨床放射線 Volume: 58 Pages: 885-888
  • Peer Reviewed
• [Journal Article] Therapeutic response to a new enzyme-targeting radiosensitization treatment (KORTUC-SC) for patients with chemotherapy-resistant supraclavucular lymph node metastasis (2013)
  • Author(s): Aoyama N, Ogawa Y, Kubota K, Ohgi K, Kataoka Y, Miyatake K, Tadokoro M, Yamanishi T, Ohnishi T, Hamada N, Kariya S, Tamura T, Nogami M, Nishioka A, Onogawa M, Miyamura M
  • Journal Title: Journal of Cancer Research & Therapy Volume: 1(9) Pages: 215-219
  • Peer Reviewed
• [Presentation] Safety and effectiveness of a new enzyme-targeting radiosensitization treatment (KORTUC II) for intratumoral injection for low-LET radioresitant tumors (2015)
  • Author(s): Ogawa Y, Kubota K, Aoyama N, Nishioka A
  • Organizer: 15th International Congress of Radiation Reaserch
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-05-27
  • Int'l Joint Research
• [Presentation] Safety and effectiveness of a new enzyme-targeting radiosensitization treatment (KORTUC II) for intratumoral injection for low-LET radioresistant tumors (2015)
  • Author(s): Ogawa Y, Kubota K, Aoyama N, Nishioka A
  • Organizer: 15th International Congress of Radaition Research
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-05-27
  • Invited
• [Presentation] Non-surgical breast-conservation treatment using KORTUC for patients with stage I/II breast cancer (2014)
  • Author(s): Ogawa Y, Kubota K, Aoyama N, Nishioka A
  • Organizer: 15th Asia-Oceaniaｎ Congress of Radiology
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2014-09-24
• [Presentation] PET-CT-guided non-surgical chemo-radiosensitization treatment (KORTUC II) for patients with locally advanced breast cancer (2014)
  • Author(s): 小川恭弘、久保田 敬、青山信隆、仰木健太、田所導子、山西伴明、刈谷真爾、野上宗伸、西岡明人、宮村充彦
  • Organizer: 第73回日本医学放射線学会学術発表会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-04-10 – 2014-04-13
• [Book] 新しい酵素標的・増感放射線療法KORTUCの基礎と臨床 (2015)
  • Author(s): 小川 恭弘
  • Total Pages: 184
  • Publisher: 篠原出版新社
• [Remarks] http//www.kochi-ms.ac.jp/～kortu/
• [Patent(Industrial Property Rights)] ハイドロゲルを担体として過酸化水素を徐放する腫瘍内局注用の (2013)
  • Inventor(s): 小川恭弘ほか
  • Industrial Property Rights Holder: 小川恭弘ほか
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-028413
  • Filing Date: 2013-04-01