2013 Fiscal Year Research-status Report
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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| 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, 特任講師 (40439253)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | Computational Model / Cancer / Inflammation / TNF / TRAIL / RIP1 / PKC / Dynamical Approach |
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| Research Abstract |
In major illnesses, such as rheumatoid arthritis and certain cancers, the expression of TNF is elevated. We developed a computational model of TNF signaling, and predicted RIP1 KO is key to down regulate key proinflammatory genes. Next, we experimentally inhibited RIP1 through Nec-1, and investigated 10 proinflammatory genes belonging to the 3 major groups of upregulated genes. As predicted by the model, all measured genes were significantly impaired. Overall, the results demonstrated that Nec-1 may potentially be used as a therapeutic target for inflammatory diseases [1].
Previously, we developed a dynamic computational model, based on perturbation-response approach, and predicted protein kinase C (PKC) as the most effective target, with over 95% capacity to kill human fibrosarcoma (HT1080) in TRAIL stimulation (Piras, V. et al. 2011). Here, to validate the prediction, which has significant implications for cancer treatment, we conducted experiments on HT1080 and HT29 cancers. Using PKC inhibitor Bisindolylmaleimide I, we demonstrate cell viability is significantly impaired with over 95% death of both cancers. Furthermore, our data suggests that PKCδ is the best single candidate for cancer suppression. [12].
To understand heterogeneous response and variability between single cells, we are now extending our research to analyze stochastic modeling of cancer cell response.
1. Hayashi K, Tabata S, Tomita M & Selvarajoo K (2014, submitted)
2. Hayashi K, Piras V, Tabata S, Tomita M & Selvarajoo K (2013) Cell Commun Signal; 11:84.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
To our delight, the project is moving ahead of time with 1 paper already published and 1 paper under review.
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| Strategy for Future Research Activity |
The plan written on the original research grant application is progressing as planned. No changes apart from the fact that we have progressed at a faster pace.
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| Expenditure Plans for the Next FY Research Funding |
The original approved budget was slightly lower than what was applied for the first year (applied for 400,000yen for equipment, 1,800,000yen for consumables and 600,000yen for travel, total = 2,700,000yen for FY2013). What was approved was for 2,300,000yen. Therefore, we reduced some consumables and travel cost to fit the lower budget. Incidentally, we spent lower than this (approx. 1,600,000 yen).
The usage plan for FY2014 is similar to the grant application (i.e. 500,000yen for consumables and 400,000yen for travel costs). We will follow this plan. The additional 688,133yen carried forward to FY2014 can be used for additional consumables or to invite international visitors for to provide talks for the next symposium on Complex Biodynamics and Networks (see Remarks section).
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Research Products
(8 results)
