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Study On Cell Apoptosis Based On Bifurcation And Sensitivity Analysis

Posted on:2020-07-05Degree:MasterType:Thesis
Country:ChinaCandidate:Y JiangFull Text:PDF
GTID:2370330599965001Subject:Applied Mathematics
Abstract/Summary:PDF Full Text Request
Apoptosis is a natural or physiological death process that occurs under the control of a series of endogenous genes.In cell death,apoptosis is a unique form of cell death.Apoptosis is different from cell necrosis.Apoptosis is not a passive process,but an active process involving the activation of a series of genes.The role of expression and regulation,etc.,is not a phenomenon of autologous injury under pathological conditions,but a death process that is actively sought to better adapt to the living environment.Apoptosis plays an important role in the growth and development of multicellular living organisms,maintaining the steady-state swelling of the body,and maintaining normal immune function.The uncontrolled proliferation of cells is closely related to the production of tumors.Many malignant tumors are free from the control of apoptosis and thus have the ability to proliferate indefinitely.In recent years,the development of anti-tumor drugs targeting the apoptotic pathway is a hot field in cancer research.Traditional medicines contain many anti-tumor active ingredients.Searching for highly effective,low-toxic and targeted apoptosis-inducing drugs will definitely be the new target of anti-cancer research.Therefore,studying the regulation mechanism of apoptosis signaling pathway is of great significance for the development of tumor drugs.Apoptosis plays an important role in embryonic development and adult tissue homeostasis.Existing studies have shown that there are multiple feedback loops that regulate apoptosis.However,how they coordinate apoptosis is still difficult to determine.Some publications have reported knockout of caspase 3 and 7 affects CytoC release,while others report inhibition of caspase activity does not affect BAX activation or mitochondrial release.Due to these inconsistencies,the model do not incorporate feedback from caspases to the amplifier module.The function of the amplifier module only transfers the signal from mitochondrial BAX to the caspase in the cytoplasm.We analyze the parameter sensitivity by the movement of the bifurcation point.For the amplifier module,bifurcation does not occur and therefore the bifurcation-based sensitivity analysis can not be performed.The intrinsic pathway of apoptosis is divided into three modules: the starter module,the amplifier module,and the actuator module.In this paper,the promoter module and actuator module are mainly analyzed based on bifurcation and single parameter sensitivity analysis to identify important regulation processes in apoptosis.It has been found through research that the network function of apoptosis is determined by the module or feedback loop,rather than by a specific parameter,and the activity of BH3 plays a more important role in the starter module and triggers the amplifier module.In addition,aC9 autocrine expression and C9 / XIAP feedback loops are more sensitive in the execution module.In addition,the three feedback loops of BH3AC/BH3 DR,MDM2/ARF/ASPP,and p53helper/p53 killer play a more important role in cell fate decision after DNA damage.The research results in this paper provide a reasonable basis for the design of clinical trials of anticancer drugs.
Keywords/Search Tags:Apoptosis, Sensitivity Analysis, Intrinsic Pathway, Bifurcation
PDF Full Text Request
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