Physical Dynamics of Cancer Response to Chemotherapy in 3D Microenvironments
3D 微环境中癌症对化疗反应的物理动力学
基本信息
- 批准号:9762592
- 负责人:
- 金额:$ 79.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-25 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAcidityAddressAffectApoptosisBiomedical EngineeringBiopsyBiopsy SpecimenBioreactorsBreastBreast Cancer cell lineCell Culture TechniquesCell LineCellular SpheroidsChemicalsClinical assessmentsComplexComputer SimulationCoupledDevelopmentDimensionsDiseaseDoseEngineeringExperimental ModelsExposure toExtracellular MatrixFeedbackGoalsGrowthGrowth and Development functionHumanIn VitroIntercellular FluidLab-On-A-ChipsMalignant NeoplasmsMammary NeoplasmsMeasurementMetabolicMethodologyMethodsMicrofluidic MicrochipsModelingMonitorMorphologyNecrosisNormal tissue morphologyNutrientOrganoidsOutcomeOutcome StudyPatientsPatternPharmaceutical PreparationsPharmacotherapyPrediction of Response to TherapyPrimary NeoplasmPropertyResolutionRunningSystemTechnologyTherapeuticThickTissuesTracerTumor TissueTumor-Derivedanticancer treatmentbasechemotherapydesigndrug efficacyimprovedin vitro Modelin vivoin vivo Modelmalignant breast neoplasmmathematical modelnovelorgan on a chippersonalized predictionspersonalized therapeuticphysical sciencepre-clinicalpredictive testpressurepublic health relevancereconstructionresponsesenescenceside effectsimulationtherapeutic developmentthree dimensional cell culturetreatment responsetumortumor growthtumor microenvironmenttumorigenic
项目摘要
DESCRIPTION (provided by applicant): These studies aim to develop a new computationally driven platform to examine complex physical and chemical microenvironments utilizing organ-on-chip microfluidic bioreactor technology coupled with a predictive mathematical model of tumor growth and therapeutic response. Malignant breast tumors are highly heterogeneous in terms of their cellular composition, varying levels of oxygenation, acidity, and nutrients, as well
as local changes in the extracellular matrix. Furthermore, tumor tissue and tumor microenvironment properties can dynamically evolve not only during tumor growth but also when anticancer treatments are administered. Despite this, nearly all pre-clinical assessments of drug efficacy and optimal dosing are performed using homogeneous 2D cell cultures that do not resemble the cellular, metabolic, and physical features manifest in tumors in vivo. Such approach suffered from overly reductionist ex vivo / in vitro studies may not fully recapitulate th complexity of cancers especially the physical and chemical microenvironment. To address these issues we propose to develop an integrated quantitative platform that combines the power of organ-on-chip 3D tissue bioreactor, developed to include non-uniform fully controlled physical and chemical microenvironments, together with a 3DMultiCel math model that allows predictive testing of a broad range of microenvironmental combinations around the experimentally validated baseline. To achieve this goal in a quantitative way we have formed a transdisciplinary team consisting of cancer biologists, biomedical engineers and mathematicians, who will develop an experimental platform for individualized anticancer treatment based on physical science principles. Our long-term goal is to provide a computationally driven "lab-on-chip" platform for 3D organotypic cultures derived from patients' tumor biopsies that will be exposed to fully controlled but dynamically variable microenvironments that will be used to optimize personalized therapeutic treatments that effectively provoke breast tumor regression with minimized harmful side effects for surrounding normal tissue. Outcomes of this study will be: (i) an improved experimental platform that combines 3D culture of tumor organoids coupled with validated predictive mathematical models for the growth and response of human breast tumor organoids within realistic microenvironments; and (ii) quantitative methods that allow one to assess the dynamics of breast tumor organoid development and response to anti-tumor treatments, using mathematical modeling. Our aims are: 1. Develop a predictive methodology to assess effects of defined microenvironments on the dynamics of normal and tumorigenic breast organoids and their sensitivity to therapeutics; 2. Construct and validate in silico model-guided complex spatial and temporal microenvironmental gradients established within TTb-G reactor, and assess breast tumor organoids response to chemotherapeutics. 3. Apply our integrated computational/engineering approach to guide therapy and predict therapeutic response ex vivo and in vivo.
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hyperpolarized NMR Spectroscopy: d-DNP, PHIP, and SABRE Techniques.
- DOI:10.1002/asia.201800551
- 发表时间:2018-05-23
- 期刊:
- 影响因子:0
- 作者:Kovtunov KV;Pokochueva EV;Salnikov OG;Cousin SF;Kurzbach D;Vuichoud B;Jannin S;Chekmenev EY;Goodson BM;Barskiy DA;Koptyug IV
- 通讯作者:Koptyug IV
Parahydrogen-Induced Magnetization of Jovian Planets?
- DOI:10.1021/acsearthspacechem.9b00326
- 发表时间:2020-04-16
- 期刊:
- 影响因子:3.4
- 作者:Chekmenev EY
- 通讯作者:Chekmenev EY
Microenvironmental Niches and Sanctuaries: A Route to Acquired Resistance.
- DOI:10.1007/978-3-319-42023-3_8
- 发表时间:2016
- 期刊:
- 影响因子:0
- 作者:Perez-Velazquez, Judith;Gevertz, Jana L.;Karolak, Aleksandra;Rejniak, Katarzyna A.
- 通讯作者:Rejniak, Katarzyna A.
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LISA Joy MCCAWLEY其他文献
LISA Joy MCCAWLEY的其他文献
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{{ truncateString('LISA Joy MCCAWLEY', 18)}}的其他基金
Organ-on-chip bioreactors for recreating breast to brain metastases
用于重建乳腺至脑转移瘤的器官芯片生物反应器
- 批准号:
10416014 - 财政年份:2021
- 资助金额:
$ 79.15万 - 项目类别:
Organ-on-chip bioreactors for recreating breast to brain metastases
用于重建乳腺至脑转移瘤的器官芯片生物反应器
- 批准号:
10173462 - 财政年份:2021
- 资助金额:
$ 79.15万 - 项目类别:
Physical Dynamics of Cancer Response to Chemotherapy in 3D Microenvironments
3D 微环境中癌症对化疗反应的物理动力学
- 批准号:
9150548 - 财政年份:2015
- 资助金额:
$ 79.15万 - 项目类别:
Physical Dynamics of Cancer Response to Chemotherapy in 3D Microenvironments
3D 微环境中癌症对化疗反应的物理动力学
- 批准号:
9024313 - 财政年份:2015
- 资助金额:
$ 79.15万 - 项目类别:
Physical Dynamics of Cancer Response to Chemotherapy in 3D Microenvironments
3D 微环境中癌症对化疗反应的物理动力学
- 批准号:
9543230 - 财政年份:2015
- 资助金额:
$ 79.15万 - 项目类别:
Matrix Metalloproteinase Regulation of Leukocyte Infiltration during Wound Repair
伤口修复过程中基质金属蛋白酶对白细胞浸润的调节
- 批准号:
8326164 - 财政年份:2010
- 资助金额:
$ 79.15万 - 项目类别:
Matrix Metalloproteinase Regulation of Leukocyte Infiltration during Wound Repair
伤口修复过程中基质金属蛋白酶对白细胞浸润的调节
- 批准号:
8727028 - 财政年份:2010
- 资助金额:
$ 79.15万 - 项目类别:
Matrix Metalloproteinase Regulation of Leukocyte Infiltration during Wound Repair
伤口修复过程中基质金属蛋白酶对白细胞浸润的调节
- 批准号:
8534852 - 财政年份:2010
- 资助金额:
$ 79.15万 - 项目类别:
Matrix Metalloproteinase Regulation of Leukocyte Infiltration during Wound Repair
伤口修复过程中基质金属蛋白酶对白细胞浸润的调节
- 批准号:
8145679 - 财政年份:2010
- 资助金额:
$ 79.15万 - 项目类别:
Matrix Metalloproteinase Regulation of Leukocyte Infiltration during Wound Repair
伤口修复过程中基质金属蛋白酶对白细胞浸润的调节
- 批准号:
7987568 - 财政年份:2010
- 资助金额:
$ 79.15万 - 项目类别:
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