Enhanced radiation response andn inhibition of angiogenesis by artificial oxygen carrier

• Project/Area Number: 18591560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Keio University
• Principal Investigator: HORINOUCHI Hirohisa Keio University, 医学部, 准教授 (60173647)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Kouichi 慶應義塾大学, 医学部, 名誉教授 (80051704) ; IZUMI Yotarou 慶應義塾大学, 医学部, 助教 (90245506) ; IKEDA Tatsuo 慶應義塾大学, 医学部, 助教 (00383802)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 低酸素 / 癌 / 酸素消費率 / 人工酸素運搬体 / 腫瘍循環 / 放射線治寮 / 放射線治療

Research Abstract

低酸素環境で増殖する悪性腫瘍に対し、腫瘍組織を酸素加すると、放射線の治療効果を増強できる可能性がある。我々が開発している人工酸素運搬体(アルブミンヘム)は分子状で、腫瘍循環でガス交換が可能と考えられ、実験腫瘍の酸素分圧を上昇させる効果がある。Donryu rat右大腿に腹水肝癌株LY80を移植し頸動脈的にHb 小胞体を投与して腫瘍を酸素加し、照射を加えるモデルを作成した。腫瘍移植後6日目に、腫瘍を酸素加、照射の効果を検討したところ、腫瘍の成長遅延を認め、放射線照射の抗腫瘍効果を増強することが明らかとなった。腫瘍血管については血管密度が減少している可能性が示唆された。

Research Products

• [Journal Article] Review of hemoglobinvesicles as artificial oxygen carriers (2009)
  • Author(s): Sakai H, Sou K, Horinouchi H, Kobayashi K, Tsuchida E.
  • Journal Title: Artif Organs 33 Pages: 139-145
• [Journal Article] Hemoglobin vesicles and red blood cells as carriers of carbon monoxide prior to oxygen for resuscitation after hemorrhagic shock in a rat model (2009)
  • Author(s): Sakai H, Horinouchi H , Tsuchida E, Kobayashi K.
  • Journal Title: Shock 31 Pages: 507-514
• [Journal Article] Histopathological changes of rat brain after direct injection of Hb-vesicles (artificial oxygen carriers) and neurological impact in an intracerebral hemorrhage model (2008)
  • Author(s): Sakai H, Okamoto M, Ikeda E, Horinouchi H, Kobayashi K, Tsuchida E.
  • Journal Title: J Biomed Mater Res A.(Epub ahead of print)
• [Journal Article] Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme' (2008)
  • Author(s): Horinouchi H , Yamamoto H, Komatsu T, Huang Y, Tsuchida E, Kobayashi K.
  • Journal Title: Cancer Sci.(Epub 2008 Apr 21.) 99(6) Pages: 1274-1278
  • NAID: 10024007807
• [Journal Article] Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation (2008)
  • Author(s): Yamamoto M, Izumi Y, Horinouchi H , Teramura Y, Sakai H, Kohno M, Watanabe M, Kawamura M, Adachi T, Ikeda E, Takeoka S, Tsuchida E, Kobayashi K.
  • Journal Title: JSurg Res(Epub 2008Jan 17) 151(1) Pages: 48-54
• [Journal Article] Enhanced radiation response of a solid tumor with the a rtificial 0xygen carrier'albumin-heme'. (2008)
  • Author(s): Horinouchi H, Yamamoto H, Komatsu T, Huang Y, Tsuchida E, Kobayashi K.
  • Journal Title: Cancer science 99 Pages: 1274-1278
  • Peer Reviewed
• [Journal Article] Systemic Administration of Hemoglobin Vesicle Elevates Tumor Tissue Oxygen Tension and Modifies Tumor Response to Irradiation. (2008)
  • Author(s): Yamamoto M, Izumi Y, Horinouchi H, Teramura Y, Sakai H, Kohno M, Watanabe M, Kawamura M, Adachi T, Ikeda E, Takeoka S, Tsuchida E, Kobayashi K
  • Journal Title: J Surg Res E-pub
  • Peer Reviewed
• [Journal Article] An enhanced radiation response of solid tumor with the artificial oxygen carrier"allbumin-heme"(rHSA-FeP) (2008)
  • Author(s): Horinouchi H, Yamamoto H, Komatsu T, Huang Y, Tsuchida E, Kobayashi K
  • Journal Title: Cancer Science 99(6) Pages: 1274-1278
  • Peer Reviewed
• [Journal Article] Haemoglobin-vesicles as artificial oxygen carriers : present situation and future visions (2007)
  • Author(s): Sakai H, Sou K, Horinouchi H , Kobayashi K, Tsuchida E.
  • Journal Title: J Intern Med(Epub 2007 Nov 27. Review) 263 Pages: 4-15
• [Journal Article] Effect of hemoglobin vesicle, a cellular-type artificial oxygen carrier, on middle cerebral artery occlusion- and arachidonic acid-induced stroke models in rats (2007)
  • Author(s): Komatsu H, Furuya T, Sato N, Ohta K, Matsuura A, Ohmura T, Takagi S, Matsuura M, Yamashita M, Itoda M, Itoh J, Horinouchi H , Kobayashi K.
  • Journal Title: Neurosci Lett(Epub 2007 Jun 2) 421(2) Pages: 121-125
• [Journal Article] One-year observation of Wistar rats after intravenous infusion of hemoglobin-vesicles (artificial oxygen carriers) (2007)
  • Author(s): Sakai H, Tsuchida E, Horinouchi H , Kobayashi K.
  • Journal Title: Artif Cells Blood Substit Immobil Biotechnol 35(1) Pages: 81-91
• [Journal Article] Influence of O(2)-carrying plasma hemoprotein "albumin-heme" on complement system and platelet activation in vitro and physiological responses to exchange transfusion (2007)
  • Author(s): Komatsu T, Huang Y, Wakamoto S, Abe H, Fujihara M, Azuma H, Ikeda H, Yamamoto H, Horinouchi H , Kobayashi K, Tsuchida E.
  • Journal Title: J Biomed Mater Res A. 81(4) Pages: 821-826
• [Journal Article] Fluid resuscitation with hemoglobin-vesicle solution does not increase hypoxia orinflammatory responses in moderate hemorrhagic shock (2006)
  • Author(s): Goto Y, Terajima K, Tsueshita T, Miyashita M, Horinouchi H , Sakai H, Tsuchida E, Sakamoto A.
  • Journal Title: Biomed Res 27(6) Pages: 283-288
  • NAID: 130004470673
• [Journal Article] Hemoglobin-vesicles as atransfusion alternative (2006)
  • Author(s): Tsuchida E, Sakai H, Horinouchi H , Kobayashi K.
  • Journal Title: Artif Cells Blood Substit Immobil Biotechnol(Review) 34(6) Pages: 581-588
• [Journal Article] PEGylated albumin-heme as an oxygen-carrying plasma expander : Exchange transfusion into acute anemia rat model (2006)
  • Author(s): Huang Y, Komatsu T, Yamamoto H, Horinouchi H , Kobayashi K, Tsuchida E.
  • Journal Title: Biomaterials 27(25) Pages: 4477-4483
• [Journal Article] PEGylated albumin-heme as an oxygen-carrying plasma expander : Exchange transfusion into acute anemia rat model. (2006)
  • Author(s): Huang Y, Komatsu T, Yamamoto H, Horinouchi H, Kobayashi K, Tsuchida E
  • Journal Title: Biomaterials 27・25 Pages: 4477-4483
• [Journal Article] 胸腺上皮性腫瘍の外科治療成績 (2006)
  • Author(s): 堀之内宏久, 朝倉啓介, 木村吉成, 竹内健, 川村雅文, 渡辺真純, 江口圭介, 小林紘一
  • Journal Title: 日本外科学会雑誌 107・6 Pages: 262-267
  • NAID: 110004852494
• [Presentation] A Study on oxygen diffusion and oxygen consumption in vessel wall of tumor microcirculation (2009)
  • Author(s): Sasaki N, Murakami R, Horinouchi H, Minamitani H
  • Organizer: 第34回日本微小循環学会年次総会
  • Place of Presentation: 北里大学薬学部コンベンションホール
  • Year and Date: 2009-02-20
• [Presentation] マウス出血性ショック時における人工赤血球投与の脳酸素分圧への影響 (2008)
  • Author(s): 冨田裕, 鳥海春樹, TatarishviliJemal, 冨田稔, 畝川美悠紀, 酒井宏水, 土田英俊, 堀之内宏久, 小林紘一, 鈴木則宏
  • Organizer: 第20回脳循環代謝学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-06
• [Presentation] 輸血代替としての利用法マウス肺切除+周術期出血モデルでのヘモグロビン小胞体投与の有効性の検討 (2008)
  • Author(s): 河野光智, 竹田貴, 堤恭介, 池田達彦, 泉陽太郎, 渡辺真純, 堀之内宏久, 小林紘一, 酒井宏水, 土田英俊
  • Organizer: 第15回日本血液代替物学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] 輸血代替としての利用法 血管損傷による制御不能出血性ショックの蘇生 人工酸素運搬体の効果について (2008)
  • Author(s): 堀之内宏久, 勢司泰久, 河野光智, 泉陽太郎, 酒井宏水, 小林紘一, 土田英俊
  • Organizer: 第15回日本血液代替物学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] 輸血代替としての利用法 腎傷害による制御不能出血モデルに対するヘモグロビン小胞体の蘇生効果 (2008)
  • Author(s): 勢司泰久, 堀之内宏久, 相川直樹, 酒井宏水, 土田英俊, 小林紘一
  • Organizer: 第15回日本血液代替物学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] 輸血代替としての利用法 Beagle 犬を用いた40%脱血ショックにおけるHb 小胞体の蘇生効果および中長期生存後の安全性の検討 (2008)
  • Author(s): 池田達彦, 堀之内宏久, 井澤菜緒子, 河野光智, 泉陽太郎, 渡辺真純, 川村雅文, 宗慶太郎, 酒井宏水, 土田英俊, 小林紘一
  • Organizer: 第15回日本血液代替物学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] ガスキャリアとしての人工酸素運搬体と肺循環 (2008)
  • Author(s): 堀之内宏久
  • Organizer: 第15回日本血液代替物学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-23
• [Presentation] Enhanced radiation response by artificial oxygen carrier (2008)
  • Author(s): Hirohisa Horinouchi, Hisashi Yamamoto, Takayo Oba, Mizuha Haraguchi, Koichi Kobayashi, Teruaki Komatsu, Eishun Tsuchida
  • Organizer: ISOTT2008
  • Place of Presentation: Sapporo
  • Year and Date: 2008-08-05
• [Presentation] Molecular artificial oxygen carrier“albumin-heme"can en hance radiation response of solid tumor. Experimental in vivo study. (2008)
  • Author(s): Horinouchi H, Yamamoto H, Komatsu T, Yubin Huang, Tsuchida E, Kobayashi K.
  • Organizer: 36^<th> Annual Conference of International Sosiety on Oxygen Transport to Tissue
  • Place of Presentation: Sapporo Prince Hotel
  • Year and Date: 2008-08-05
• [Book] MOOK肺癌の臨床疫学・病理・発見・診断・治療2006-2006/高齢者肺癌の外科治療 (2006)
  • Author(s): 堀之内宏久, 小林紘一
  • Total Pages: 471
  • Publisher: 篠原出版新社