Mechanism of tumor rebound after discontinuation of anti-VEGF treatment

• Project/Area Number: 15K21205
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science; Tumor biology
• Research Institution: Iwate University
• Principal Investigator: Ishiguro-Oonuma Toshina 岩手大学, 農学部, 准教授 (60452695)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血管新生 / 分子標的薬 / VEGF / 血管新生阻害薬 / 分子標的 / VEGF阻害剤 / in vivo イメージング / 腫瘍

Outline of Final Research Achievements

Mouse mammary tumor cell line 4T1 cell were used. BALB/c mice were injected with 4T1 cells and divided into 4 groups (group A: base line control, group B: 7-days treatment with sunitinib (40 mg/kg, QD), group C: 7-days treatment with sunitinib plus 7-days withdraw, group D: 7-days treatment with vehicle plus 7-days withdraw). Mice were perfused at Day1 (group A), Day7 (group B), and Day14 (group C and D) and analysed by immunohistochemistry. In the group B, a significant decrease of blood vessel density was observed. In the group C, blood vessel density was comparable with group A, that means that decreased blood vessels rapidly recovered after sunitinib withdrawal. The tumor invasiveness to surrounding tissue was much greater in group C than in group B. However, incidence of distant metastasis was comparable between group B and C.

Research Products

• [Journal Article] Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown (2017)
  • Author(s): Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A
  • Journal Title: JCI Insight Volume: 2 Issue: 3
  • DOI: 10.1172/jci.insight.90905
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ウシ栄養膜細胞系への効果的な遺伝子導入 (2016)
  • Author(s): 與座明祥，石黒（大沼）俊名，高橋 透，橋爪一善，木崎景一郎
  • Organizer: 第89回日本生化学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] ウシ栄養膜・胎膜に発現するmiRNAの探索 (2016)
  • Author(s): 與座明祥，石黒（大沼）俊名，高橋 透，橋爪一善，木崎景一郎
  • Organizer: 第109回日本繁殖生物学会大会
  • Place of Presentation: 麻生大学（神奈川県相模原市）
  • Year and Date: 2016-09-11
• [Presentation] 愛媛大学動物実験センター改修工事を経験して (2016)
  • Author(s): 石黒（大沼）俊名
  • Organizer: JCLAM Forum 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学生物資源科学部（神奈川県藤沢市）
  • Year and Date: 2016-09-06
• [Presentation] 血管新生制御因子バソヒビンのウシ子宮・胎盤における発現動態 (2016)
  • Author(s): 佐藤良平，石黒（大沼）俊名，高橋透，橋爪一善，木崎景一郎
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学生物資源科学部（神奈川県藤沢市）
  • Year and Date: 2016-09-06