Alterations of tumor microenvironment during antiangiogenic therapy in colorectal cancer
| Project/Area Number |
24390312
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Kinji 浜松医科大学, 医学部附属病院, 講師 (20324361)
OHTA Manabu 浜松医科大学, 医学部附属病院, 講師 (40397394)
KIKUCHI Hirotoshi 浜松医科大学, 医学部, 助教 (70397389)
MIYAZAKI Shinichiro 浜松医科大学, 医学部附属病院, 医員 (30571575)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
BABA Satoshi 浜松医科大学, 医学部附属病院, 准教授 (10242760)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
|
|---|
| Keywords | 抗血管新生治療 / 大腸癌 / 腫瘍微小環境 / 低酸素 / 癌悪性化 / 治療抵抗性 / 癌微小環境 / 癌幹細胞 / 分子標的治療 |
|---|
| Outline of Final Research Achievements |
Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A has been used for colorectal cancer treatment. However, a number of preclinical reports indicate the development of resistance to anti-angiogenic therapy. In this study, we addressed the effects of anti-VEGF antibodies on the growth and malignant behavior of colorectal cancer cells using an orthotopic implantation model of TK-4, a solid tumor strain derived from a colon cancer patient, into nude mice. Intratumoral hypoxia induced by anti-VEGF antibody treatment resulted in induction of stanniocalcin 2 (STC2), a target gene of hypoxia inducible factor-1 (HIF-1), to enhance colon cancer cell growth and migration. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti-VEGF antibodies and rebound phenomenon after withdrawal of bevacizumab.
|
Report
(4 results)
Research Products
(19 results)
-
-
-
[Journal Article] Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid Alterations in Gastric Cancer.2015
Author(s)
Uehara T, Kikuchi H, Miyazaki S, Iino I, Setoguchi T, Hiramatsu Y, Ohta M, Kamiya K, Morita Y, Tanaka H, Baba S, Hayasaka T, Setou M, Konno H
-
Journal Title
Ann Surg Oncol
Volume: In press
Issue: S2
Pages: 206-213
DOI
Related Report
Peer Reviewed
-
[Journal Article] Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts.2014
Author(s)
Miyazaki S, Kikuchi H, Iino I, Uehara T, Setoguchi T, Fujita T, Hiramatsu Y, Ohta M, Kamiya K, Kitagawa K, Kitagawa M, Baba S, Konno H
-
Journal Title
Int J Cancer
Volume: 135
Issue: 2
Pages: 295-307
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
