Nano Drag Delivery System using Tight Junction Control via Vascular Endothelial Cadherin

2008 Fiscal Year Final Research Report

• Project/Area Number: 18790920
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kansai Medical University
• Principal Investigator: KOMEMURA Atsushi Kansai Medical University, 医学部, 助教 (80360254)
• Research Collaborator: TANIGAWA Noboru 関西医科大学, 医学部, 講師 (90227215) ; KARIYA Shuji 関西医科大学, 医学部, 助教 (40368220) ; KOJIMA Hiroyuki 関西医科大学, 医学部, 助教 (30368229) ; SHOMURA Yuzo 関西医科大学, 医学部, 助教 (70298868) ; SAWADA Satoshi 関西医科大学, 医学部, 教授 (80121937)
• Project Period (FY): 2006 – 2008
• Keywords: 低侵襲治療システム

Research Abstract

凝血剤として知られるトロンビンには、血管内皮細胞同士の結合タンパクである血管内皮カドヘリン(VE-Cadherin)を抑制する事によって内皮細胞間のタイトジャンクションを急速に15〜20nm開大させ、血管透過性を著しく亢進させる作用がある事が注目されはじめた。本提案では、経カテーテル的な肝動注化学塞栓療法に使用する薬剤としてトロンビンと抗腫瘍薬の混合物を使用する。血管透過性亢進作用による抗腫瘍薬の高濃度暴露による濃度依存性効果増強と、自己凝血塊に含有された抗腫瘍薬の徐放効果による暴露時間延長による時間依存性効果増強を肝動脈塞栓術に応用する。
家兎の下腿部軟部腫瘍に対して、シスプラチン-リピオドールエマルジョンおよびトロンビン-シスプラチン-リピオドールエマルジョンの投与を行った。すなわち、家兎右大腿部にVX2腫瘍を移植し、2週間後に数cm大の腫瘍が発育していることを確認する。家兎左大腿動脈を外科的に露出させ、マイクロカテーテルを左大腿動脈から右外腸骨動脈に挿入する。右外腸骨動脈からの腫瘍への血流を確認した後、シスプラチン-リピオドールエマルジョンまたはトロンビン-シスプラチン-リピオドールエマルジョンの投与を行った。投与量としてシスプラチンは1mg/kg、リピオドールは0.1ml/kg、トロンビンは100u/kgの投与を行った。投与5分後および投与10分後の血清中シスプラチン濃度、および投与60分後の腫瘍組織内シスプラチン濃度を測定した。
トロンビンを投与した群において、血清中へのシスプラチンの流出が抑制され、また、組織内への高濃度のシスプラチンの残留傾向を認めた。

Research Products

• [Journal Article] Composite Material Stent Comprising Metallic Wire and Polylactic Acid Fibers, and its Mechanical Strength and Retrievability (2009)
  • Author(s): Shomura Y, Tanigawa N, Tokuda T, Kariya S, Kojima H, Komemushi A, Sawada S
  • Journal Title: Acta Radiol 20 Pages: 1-5
• [Journal Article] Transcatheter coil embolization for steal syndrome in patients with hemodialysis access (2009)
  • Author(s): Kariya S, Tanigawa N, Kojima H, Komemushi A, Shomura Y, Shiraishi T, Kawanaka T, Sawada S
  • Journal Title: Acta Radiol 50(1) Pages: 28-33
• [Journal Article] High-flow priapism undergoing arterial embolization : review of literature following American Urological Association guideline on the management of priapism (2009)
  • Author(s): Kojima H, Tanigawa N, Kariya S, Komemushi A, Shomura Y, Yanishi M, Murota T, Sawada S
  • Journal Title: Minim Invasive Ther Allied Technol 18(1) Pages: 1-5
• [Journal Article] Cerebral microembolisation during radiofrequency ablation of lung tumours : detection by carotid duplex ultrasound (2009)
  • Author(s): Tanigawa N, Kariya S, Kojima H, Komemushi A, Shomura Y, Ikeda K, Omura N, Tokuda T, Maehara M, Terada J, Sawada S
  • Journal Title: Br J Radiol 82(975) Pages: 249-53
• [Journal Article] Improvement in respiratory function by percutaneous vertebroplasty (2008)
  • Author(s): Tanigawa N, Kariya S, Kojima H, Komemushi A, Shomura Y, Tokuda T, Ueno Y, Kuwata S, Fujita A, Terada J,Sawada S
  • Journal Title: Acta Radiol 49(6) Pages: 638-43
• [Journal Article] Diffusion-weighted imaging for predicting new compression fractures following percutaneous vertebroplasty (2008)
  • Author(s): Sugimoto T, Tanigawa N, Ikeda K, Ohmura N, Maehara M, Kariya S, Kojima H, Komemushi A, Ha-Kawa SK, Saito Y, Tajika A, Kinoshita T, Sawada S
  • Journal Title: Acta Radiol 49(4) Pages: 419-26
• [Journal Article] Intraosseous Venography with Carbon Dioxide in Percutaneous Vertebroplasty : Carbon Dioxide Retention in Renal Veins (2008)
  • Author(s): Komemushi A, Tanigawa N, Kariya S, Kojima H, Shomura Y, Tokuda T, Nomura M, Terada J, Kamata M, Sawada S
  • Journal Title: Cardiovasc Intervent Radiol 31(6) Pages: 1174-7
• [Journal Article] Biochemical markers of bone turnover in percutaneous vertebroplasty for osteoporotic compression fracture (2008)
  • Author(s): Komemushi A, Tanigawa N, Kariya S, Kojima H, Shomura Y, Tokuda T, Nomura M, Terada J, Kamata M, Sawada S
  • Journal Title: CardioVascular & Interventional Radiology 31(2) Pages: 332-5
• [Journal Article] Relationship between cement distribution pattern and new compression fracture after percutaneous vertebroplasty (2007)
  • Author(s): Tanigawa N, Komemushi A, Kariya S, Kojima H, Shomura Y, Omura N, Sawada S
  • Journal Title: AJR Am J Roentgenol 189(6) Pages: W348-52
• [Journal Article] Lower limb ischaemia caused by fractured osteochondroma of the femur (2007)
  • Author(s): Tanigawa N, Kariya S, Kojima H, Komemushi A, Fujii H, Sawada S
  • Journal Title: Br J Radiol 80(952) Pages: 78-80
• [Journal Article] Primary Patency with Cutting and Conventional Balloon Angioplasty for Different Types of Hemodialysis Access Stenosis (2007)
  • Author(s): Kariya S, Tanigawa N, Kojima H, Komemushi A, Shomura Y, Shiraishi T, Kawanaka T, Sawada S
  • Journal Title: Radiology 243(2) Pages: 578-87
• [Journal Article] Clinical impact of multidetector row computed tomography on patients with pancreatic cancer (2007)
  • Author(s): Satoi S, Yamamoto H, Takai S, Tanigawa N, Komemushi A, Yanagimoto H, Toyokawa H, Matsui Y, Mergental H, Kamiyama Y
  • Journal Title: Pancreas 34(2) Pages: 175-9
• [Presentation] Effect of Percutaneous Vertebroplasty Combined with Intensity-modulated Radiotherapy : A Phantom Study (2008)
  • Author(s): Motoo Nomura, Atsushi Komemushi, Minoru Kamata, Noboru Tanigawa, Hiroyuki Kojima, Satoshi Sawada
  • Organizer: RSNA2008
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20081130-1205
• [Presentation] Comparison of embolic behavior and absorption process between gelatin sponge microspheres and water-soluble polyvinyl alcohol (PVA) microspheres in pig liver model (2008)
  • Author(s): Y.Shomura, N.Tanigawa, M.Shibutani, T.Tokuda, J.Terada, S.Kariya, H.Kojima, A.Komemushi, S.Sawada
  • Organizer: CIRSE 2008
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 20080913-17
• [Presentation] Transcatheter embolization of pseudoaneurysms in visceral and peripheral arteries (2008)
  • Author(s): T.Tokuda, N.Tanigawa, Y.Shomura, S.Kariya, H.Kojima, S.Sawada, A.Komemushi, J.Terada
  • Organizer: CIRSE 2008
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 20080913-17
• [Presentation] Does Bone Cement Injected to Vertebra Affect Radiotherapy Dose Distribution? (2008)
  • Author(s): M. Nomura, A. Komemushi, M. Kamata, N. Tanigawa, Y. Hori, S. Sawada, M. Arakawa, M. Nakashuji, S. Kariya, H.Kojima, Y. Shomura, T. Tokuda, J. Terada
  • Organizer: SIR 2008
  • Place of Presentation: Washington, D.C., U.S.A
  • Year and Date: 20080315-20
• [Presentation] The Location of Parotid Gland Tumors : Evaluation with Parotid Tractography Using 3-tesla MRI (2007)
  • Author(s): Koshi Ikeda, Naoto Ohmura, Hiroaki Kurokawa, Atsushi Komemushi, Yoko Harima, Satoshi Sawada
  • Organizer: RSNA2007
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20071125-30
• [Presentation] Prospective Analysis of Respiratory Function Following Percutaneous Vertebroplasty (2007)
  • Author(s): Noboru Tanigawa, Shuji Kariya, Hiroyuki Kojima, Atsushi Komemushi, Yuzo Shomura, Satoshi Sawada
  • Organizer: RSNA2007
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20071125-30
• [Presentation] Prediction of Progression and Metastasis of Advanced Cervical Cancers after Radiotherapy According to Expression Profiles of 69 Genes Selected by Microarray Analysis (2007)
  • Author(s): Yoko Harima, Minoru Kamata, Atsushi Komemushi, Koshi Ikeda, Satoshi Sawada
  • Organizer: RSNA2007
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20071125-30
• [Presentation] Yuzo Shomura, Takanori Tokuda, Noboru Tanigawa, Hiroyuki Kojima, Shuji Kariya, Atsushi Komemushi (2007)
  • Author(s): An Arterial Stent Graft Covered with an Electro-spun Nanofiber Sleeve : Structural Characteristics and in Vivo Behavior in Pig Model
  • Organizer: RSNA2007
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20071125-30
• [Presentation] Fistulography Using Carbon Dioxide in Percutaneous Transluminal Angioplasty for Hemodialysis Access Failure : A Prospective Evaluation (2007)
  • Author(s): Shuji Kariya, Noboru Tanigawa, Hiroyuki Kojima, Atsushi Komemushi, Yuzo Shomura, Hiroshi Yamamoto
  • Organizer: RSNA2007
  • Place of Presentation: McCormick Place, Chicago, U.S.A
  • Year and Date: 20071125-30
• [Presentation] Artificial blood vessel of composite material knitted core and electrospun nanofiber sleeve : evaluation of structural characteristics and biocompatibility in pig model (2007)
  • Author(s): T.Tokuda, Y.Shomura, A.Komemushi, S.Kariya, N.Tanigawa, S.Sawada
  • Organizer: CIRSE 2007
  • Place of Presentation: Athens, Greece
  • Year and Date: 20070908-12
• [Presentation] Cement leakage in percutaneous vertebroplasty for osteoporotic compression fracture with or without intravertebral clefts (2007)
  • Author(s): N. Tanigawa, A. Komemushi, S. Kariya, H. Kojima, Y. Shomura, T. Tokuda, H. Yamamoto, S. Sawada
  • Organizer: CIRSE 2007
  • Place of Presentation: Athens, Greece
  • Year and Date: 20070908-12
• [Presentation] Percutaneous vertebroplasty for osteoporotic compression fracture, First 500 levels of a single center : Long term evaluation of the technical and clinical outcomes (2007)
  • Author(s): N.Tanigawa, S.Kariya, Y.Shomura, T.Tokuda, S.Sawada, A.Komemushi
  • Organizer: SIR 2009
  • Place of Presentation: San Diego, CA, U.S.A
  • Year and Date: 20070307-12
• [Presentation] Biochemical markers of bone turnover in percutaneous vertebroplasty for osteoporotic compression fracture (2007)
  • Author(s): Atsushi Komemushi, Noboru Tanigawa, Shuji Kariya, Hiroyuki Kojima, Yuzo Shomura, Takanori Tokuda, Hiroshi Yamamoto, Satoshi Sawada
  • Organizer: SIR 2007 : 32nd Annual Scientific Meeting
  • Place of Presentation: Seattle, Washington, U.S.A
  • Year and Date: 20070301-06