Enhancing apoptosis of cancers using systems biology approach
| Project/Area Number |
25430184
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
System genome science
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| Research Institution | Keio University |
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Principal Investigator |
SELVARAJOO Kumar 慶應義塾大学, 政策・メディア研究科, 特任准教授 (40439253)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | TRAIL / Cancer / Computational Biology / Modeling / Computational Model / Apoptosis / Tumor Immunology / Systems Biology / PKC / Inflammation / TNF / RIP1 / Dynamical Approach |
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| Outline of Final Research Achievements |
Over the last decade, we have developed computational models to interpret instructive cell signaling and high-throughput transcriptome-wide behaviors of immune and cancer cells. Here, we focused to overcome cancer resistance. TRAIL (tumor necrosis factor related apoptosis-inducing ligand), a proinflammatory cytokine, has shown promising success in controlling cancer threat due to its ability to induce apoptosis in cancers specifically, while having limited effect on normal cells. Nevertheless, several malignant cancers, such as fibrosarcoma (HT1080), remain non-sensitive to TRAIL. To sensitize HT1080 to TRAIL treatment, we developed a dynamic computational model based on perturbation-response approach, to predict a crucial co-target to enhance cell death. The model simulations suggested that PKC inhibition together with TRAIL induce 95% cell death. Subsequently, we confirmed this result experimentally utilizing the PKC inhibitor, bisindolylmaleimide (BIM) I, and PKC siRNAs in HT1080.
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Report
(4 results)
Research Products
(21 results)
