Mechanisms of resistance to antiangiogenic therapy in gastrointestinal cancers.
| Project/Area Number |
22791270
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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|---|
| Keywords | 消化器癌 / 抗血管新生 / 耐性機構 / 消火器癌 / 癌微小環境 / 低酸素 |
|---|
| Research Abstract |
We transplanted solid tumors derived from human colon carcinoma into the cecum wall of nude mice and treated them with anti-VEGF antibody or normal control IgG. Despite decreased microvessel density in the tumors with anti-VEGF treatment, tumor growth was incompletely impaired. Microarray analysis revealed 97 genes that were predominantly expressed in tumors treated with anti-VEGF antibody compared with untreated tumors. Among them, we further focused on stanniocalcin 2(STC2) which has been reported to be regulated by hypoxia inducible factor-1(HIF-1) under hypoxic condition and to induce epithelial mesenchymal transition. Gene Set Enrichment Analysis(GSEA) showed the activation of transforming growth factorβ(TGFβ) pathway in tumors treated with anti-VEGF antibody. These findings suggest that hypoxic conditions due to VEGF inhibition may induce EMT and stemness of transplanted tumors, resulting in enhanced invasive and metastatic potential. Immunohistochemistry of HIF-1αand HIF-2αrevealed that HIF-1αprotein was more likely to locate in the nucleus of tumors treated with anti-VEGF antibody compared with untreatedtumors. Immunohistochemistry of colon cancer stem cell markers, CD133, CD44 and ALDH1 revealed that expression levels of ALDH1 were higher in tumors treated with anti-VEGF antibody than those in tumors treated with control IgG.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] Near-infrared multichannel Raman spectroscopy with a 1064 nm excitation wavelength for ex vivo diagnosis of gastric cancer2011
Author(s)
Kawabata T, Kikuchi H(contributed equally), Okazaki S, Yamamoto M, Hiramatsu Y, Yang J, Baba M, Ohta M, Kamiya K, Tanaka T, Konno H
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Journal Title
J Surg Res
Volume: 169
Pages: 137-43
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[Journal Article] Microarray analysis identifies versican and CD9 as potent prognostic markers in gastric gastrointestinal stromal tumors2011
Author(s)
Setoguchi T, Kikuchi H, Yamamoto M, Baba M, Ohta M, Kamiya K, Tanaka T, Baba S, Goto-Inoue N, Setou M, Sasaki T, Mori H, Sugimura H, Konno H
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Journal Title
Cancer Sci
Volume: 102
Pages: 883-9
NAID
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[Presentation] Overexpression of LPCAT1 and concomitant lipid alterations in gastric cancer2012
Author(s)
Kikuchi H, Uehara T, Setoguchi T, Yamamoto M, Ohta M, Kamiya K, Baba B, Setou M, Sugimura H, Konno H.
Organizer
American Association for Cancer Research 103nd Annual Meeting
Place of Presentation
Chicago IL, USA
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