Analysis of the effects of tumor microenvironment on the susceptibility of malignant tumors to anticancer drugs-its therapeutic application

Research Project

Project/Area Number	20591731
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Cerebral neurosurgery
Research Institution	Shimane University
Principal Investigator	TAKENAGA Keizo Shimane University, 医学部, 准教授 (80260256)
Project Period (FY)	2008 – 2010
Project Status	Completed (Fiscal Year 2010)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	脳腫瘍 / 薬剤抵抗性 / 微小環境 / アストロサイト / アストロサイ
Research Abstract	To examine whether tumor microenvironment (e.g., astrocytes and hypoxia) influence the susceptibility of glioblastoma and metastatic brain tumors to anticancer drugs, we tested cytotoxic activity of various anticancer agents against rat and human glioma cells and human mammary carcinoma cells in cocultures with rat astrocytesunder normoxic and hypoxic conditions. The results showed that temozolomide (TMZ) becomes less effective against glioma cells and metastatic brain tumor cells in the presence of astrocytes, which depends not on cellular interactions or soluble factors such as inflammatory cytokines but primarily on the ability of astrocytes to reduce the efficacy of TMZ.