2007 Fiscal Year Final Research Report Summary
Proteomic approach for personalized Medicine in cancer chemotherapy
| Project/Area Number |
18390053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
TANIGAWARA Yusuke Keio University, School of Medicine, Professor (30179832)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Sayo Keio University, School of Medicine, Instructor (90424134)
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| Project Period (FY) |
2006 – 2007
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| Keywords | personalized medecine / proteome / metabolome / biomarker / chemosensitivity / protein chip / oxaliplatin / irinotecan |
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| Research Abstract |
To improve cancer chemotherapy, personalized medicine based on the individual tumor characteristics is urgently needed. Useful biomarkers that can predict the chemosensitivity is expected to be one of the strong tools to select the optimal treatment for each patient. Colorectal cancer is a common and lethal disease, and oxaliplatin (L-OHP), irinotecan (CPT-11) and fluorouracil (5-FU)are key drugs in the treatments for colorectal cancer. We aimed to discover useful biomarkers for predicting the sensitivity to chemotherapy by proteomic and metabolomic approach.
1. Discovery of biomarkers for L-OHP sensitivity: Using various types of 11 human colorectal cancer cell lines, we evaluated the oxaliplatin sensitivity as IC50 values, and analyzed their intracellular protein expression profiles by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). By Expression Difference Mapping analysis and linear regression analysis between oxaliplatin sensitivity and
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the peak intensity of each mass detected, we found a potential protein biomarker for predicting L-OHP sensitivity which expression is well associated with L-OHP sensitivity.
2. Discovery of biomarkers for CPT-11 sensitivity: To elucidate the responsiveness of cancer cells to CPT-11, human colorectal carcinoma with low sensitivity(HT-29)or high sensitivity (HCT-116) was implanted subcutaneously into nude mice, and their serum was analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). A characteristic peak was detected between low sensitivity and high sensitivity cancer cells in the serum metabolites. It might be a useful biomarker that can reveal sensitivity of cancer to CPT-11 therapy.
3. The metabolic responsiveness of cancer cells to 5-FU exposure: Human colorectal carcinoma LS174T cells were exposed to high (100 μM) or low (2 μM) 5-FU concentration. After 0, 4, 8, and 12 h exposure, all intracellular metabolites were extracted and analyzed by CE-TOFMS. We firstly showed the dynamics of intracellular metabolites flux after 5-FU exposure. Less
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Research Products
(59 results)
