The Mechanism of Novel Delta-like 4 neutralizing antibodies to lung cancer

• Project/Area Number: 19790553
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: ASADA Masanori Tohoku University, 病院, 助教 (20396477)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,660,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 肺癌 / 血管新生 / 腫瘍血管阻害抗体 / Delta-like-4中和抗体 / 癌治療 / 血管生阻害薬 / Delta-like4中和抗体 / Ephrin B2 / Dll4中和抗体 / Notchシグナル / VEGF

Research Abstract

肺癌治療では、抗VEGF抗体など血管新生阻害剤が進行性肺癌の化学療法に併用されるが、これらの血管新生阻害剤はすべての肺癌に効果はなく、また、効果があったとしてもいずれ再発する。本研究で明らかにできたことは、新規Delta-like 4 (D114) 中和抗体がマウス肺扁平上皮癌と腺癌において腫瘍縮小作用があること、NotchシグナルだけではなくEphrinB2をして非生産的血管形成をおこし腫瘍増殖を抑える作用である。D114中和抗体がヒトの様々な癌治療でも有効である可能性がある。

Research Products

• [Journal Article] Role of ephrinB2 in non-productive angiogcnesis induccd by Delta-like 4 blockade. (2009)
  • Author(s): 矢満田慎介, 海老原覚、浅田成紀他7名
  • Journal Title: Blood 2009 113 Pages: 3631-3639
  • Peer Reviewed
• [Journal Article] Depletion of serotonin and selective inhibition of 2B receptor supprcsscd tumor angiogenesis by inhibiting endothelial nitric oxide synthase and extraccllular signal-regulated kinase 1/2 phosphorylation. (2009)
  • Author(s): 浅田成紀他6名
  • Journal Title: Neoplasia 2009 4 Pages: 408-417
  • Peer Reviewed
• [Journal Article] Role of ephrinB2 in non-productive angiogenesis induced by Delta-like 4 blockade (2009)
  • Author(s): 矢満田慎介, 他
  • Journal Title: Blood 113 Pages: 3161-3169
  • Peer Reviewed
• [Journal Article] Depletion of serotonin and selective inhibition of 2B receptor supp ressed tumor angiogenesis by inhibiting endothelial nitric oxide sy-nthase and extracellular signal-regulated kinase 1/2 phosphorylation (2009)
  • Author(s): 浅田成紀, 他
  • Journal Title: Neoplasia 4 Pages: 408-417
  • Peer Reviewed
• [Journal Article] Erythropoictin promotes the growth of tumors lacking its receptor and decreases survival of tumor-bearing mice by enhancing angiogenesis. (2008)
  • Author(s): 岡崎達馬、海老原覚、浅田成紀他3名
  • Journal Title: Nooplasia 2008 9 Pages: 932-939
  • Peer Reviewed
• [Journal Article] Erythropoietin promotes the growth of tumors lacking its receptor and decreases survival of tumor-bearing mice by enhancing angiog-enesis (2008)
  • Author(s): 岡崎達馬, 他
  • Journal Title: Neoplasia 9 Pages: 932-939
  • Peer Reviewed
• [Journal Article] Macrophage colony-stimulating factor improves cardiac function after ischemic injury by inducing vascular endothelial growth factor production and survival of cardiomyocytes. (2007)
  • Author(s): Okazaki T, Ebihara S, Asada M, et. al.
  • Journal Title: Am J Pathol. 171 Pages: 1093-1103
  • Peer Reviewed
• [Presentation] Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter (2007)
  • Author(s): Masanori Asada, Satoru Ebihara, Yohtaro Numachi, et. al.
  • Organizer: 12th World Congress on Advances in Oncology and 10th International Symposium on Molecular Medicine
  • Place of Presentation: Creta Maris, Hersonissos, Crete, Greece
  • Year and Date: 2007-11-12
• [Presentation] Role of ephrinB2 in non-productive angiogenesis induced by Dclta-like 4 blockade. (2007)
  • Author(s): 矢満田慎介、浅田成紀他4名
  • Organizer: 米国胸部疾患学会
  • Place of Presentation: サンフランシスコ(米国)
  • Year and Date: 2007-05-20
• [Presentation] Dll4 neutralization antibody reduced tumor growth (2007)
  • Author(s): Shinsuke Yamanda, Masanori Asada, Satoru Ebihara, et. al.
  • Organizer: American Thoracic Society International Confarence San Francisco
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2007-05-18