Radiation Protectors and Radiation Therapy Coupled Chemoprevention
放射防护器和放射治疗联合化学预防
基本信息
- 批准号:7846235
- 负责人:
- 金额:$ 32.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2014-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcidsAcute Myelocytic LeukemiaAddressAdultAdverse effectsAffectAlkylating AgentsAlkylating Antineoplastic AgentsAmifostineAnimal TestingAnimalsAnticarcinogenic AgentsBase PairingBiological AssayBiological AvailabilityCancer PatientCarmustineCellsChemopreventionChemopreventive AgentChemoprotective AgentChemotherapy-Oncologic ProcedureChildhoodChronicCisplatinClinicalCombined Modality TherapyComplexCoupledCouples TherapyCyclophosphamideCytoprotectionCytoprotective AgentDNA DamageDescriptorDevelopmentDiagnosisDiseaseDoseDrug usageDysmyelopoietic SyndromesEffectivenessEthylnitrosoureaEvaluationExhibitsExperimental NeoplasmsExposure toFDA approvedFrameshift MutationGeneral PopulationGenomicsGoalsGrantGuanineHead and Neck CancerHealthHematopoieticHematopoietic stem cellsHourHumanHypoxanthinesIncidenceIndividualInduced MutationInvestigationIonizing radiationKidneyKnock-in MouseLaboratoriesLateralLesionLong-Term SurvivorsLungLung noduleLymphocyteMalignant - descriptorMalignant Childhood NeoplasmMalignant NeoplasmsMalignant neoplasm of ovaryMarketingMediatingMetastasis InductionModalityModelingMolecularMonitorMusMutagenesisMutationMyeloid LeukemiaNamesNeoplasm MetastasisNoduleNon-Small-Cell Lung CarcinomaNormal CellOralPackage InsertParotid GlandPatientsPeripheral Blood LymphocytePharmaceutical PreparationsPhasePilot ProjectsPopulationPostoperative PeriodPredictive ValuePredispositionPrimary NeoplasmProcessPropertyProtocols documentationRadiationRadiation therapyRadiation-Protective AgentsRadioRegimenRelative (related person)ResourcesRiskRisk FactorsScheduleSecond Primary CancersSystemTailTestingTherapeuticTherapeutic AgentsTherapy-Related Acute Myeloid LeukemiaTherapy-Related Acute Myeloid Leukemia and Myelodysplastic SyndromeTimeToxic effectTransferaseTreatment EfficacyTreatment ProtocolsTreatment-Related CancerValidationVeinsWild Type MouseWorkXerostomiaanalogartificial lungbasecancer cellcancer preventioncancer therapycarcinogenesiscell killingchemotherapeutic agentchemotherapycytotoxicdesigndosageeffective therapyimprovedirradiationkillingsleukemialeukemogenesismouse modelneoplasticneoplastic cellnoveloncologyoutcome forecastphosphorothioatepreventpromoterpublic health relevanceradiation effectresearch studyresponsestemsuccesstreatment strategytumortumor growth
项目摘要
DESCRIPTION (provided by applicant):
The use of radiation and chemotherapy has resulted in steadily improving cure rates in both childhood and adult cancer patients. This therapeutic success, however, has been limited by the frequent development of secondary cancers in long term survivors. Examples of therapy-related cancers include myelodysplastic syndrome and acute myeloid leukemia. These neoplastic disorders are a consequence of the therapy induced- DNA damage in hematopoietic stem cells. Patients with potentially curable cancers represent a critical population for the development of strategies for chemoprevention of secondary malignancies. The goals of this proposal are the identification, characterization, and validation of agents that can prevent mutational damage in hematopoietic stem cells while preserving the anti-tumor efficacy of radiation and chemotherapy regimens. This novel paradigm of radioprotector-mediated chemoprevention is known as therapy coupled chemoprevention (TCC). To facilitate these studies, we will use the MLL-ELL knock-in mouse model that closely recapitulates the multistep process of transformation observed in human-related acute myeloid leukemia. These MLL-ELL knock-in mice do not develop leukemia spontaneously, but exhibit a high susceptibility to leukemia following exposure to a DNA damaging agent. This model will provide a novel and unique resource to test and validate TCC strategies for patients at risk for secondary cancers. TCC agents to be examined are amifostine and phosphonol, which each possess anti-mutagenic properties at doses 4- to 16- fold lower than those required to demonstrate classical cytoprotection. We will determine the maximum non- cytoprotective doses of these TCC agents in mice having 4 day old FSa "artificial" micro lung metastases treated with ionizing radiation and an alkylating-chemotherapeutic agent such as cyclophosphamide. Using the Hprt mutation assay, we will assess the anti-mutagenic effectiveness of TCC agents in MLL-ELL knock-in mice and their wild type counterparts following exposure to ionizing radiation and alkylating agent therapy. Using the MLL-ELL knock-in mouse model, we will also evaluate the efficacy of TCC to prevent radiation- and alkylating agent-induced mutations at the Hprt locus and the development of therapy-related acute myeloid leukemia in the same anima system. PUBLIC HEALTH RELEVANCE: This grant addresses the growing health problem of cancer patients cured of their first cancer by radiation and chemotherapy only to be diagnosed in later years with a cancer induced by those therapies. By appropriately administering to patients at the time of their radiation and chemotherapies cancer prevention drugs that can prevent mutations and cancer development without affecting the direct killing of cancer cells, patients will continued to be cured but without the risk of developing new cancers due to their treatments.
描述(由申请人提供):
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID J. GRDINA其他文献
DAVID J. GRDINA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID J. GRDINA', 18)}}的其他基金
Radiation Protectors and Radiation Therapy Coupled Chemoprevention
放射防护器和放射治疗联合化学预防
- 批准号:
8070528 - 财政年份:2009
- 资助金额:
$ 32.37万 - 项目类别:
Radiation Protectors and Radiation Therapy Coupled Chemoprevention
放射防护器和放射治疗联合化学预防
- 批准号:
8245173 - 财政年份:2009
- 资助金额:
$ 32.37万 - 项目类别:
Radiation Protectors and Radiation Therapy Coupled Chemoprevention
放射防护器和放射治疗联合化学预防
- 批准号:
8450913 - 财政年份:2009
- 资助金额:
$ 32.37万 - 项目类别:
Radiation Protectors and Radiation Therapy Coupled Chemoprevention
放射防护器和放射治疗联合化学预防
- 批准号:
7728207 - 财政年份:2009
- 资助金额:
$ 32.37万 - 项目类别:
相似海外基金
Computing analysis of leukemic stem cell dynamics in acute myelocytic leukemia
急性粒细胞白血病白血病干细胞动力学的计算分析
- 批准号:
19K08356 - 财政年份:2019
- 资助金额:
$ 32.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia
在急性髓细胞白血病中使用超靶向单克隆抗体产生免疫毒素
- 批准号:
23501309 - 财政年份:2011
- 资助金额:
$ 32.37万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556971 - 财政年份:1980
- 资助金额:
$ 32.37万 - 项目类别:
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556968 - 财政年份:1980
- 资助金额:
$ 32.37万 - 项目类别:
ERADICATION OF ACUTE MYELOCYTIC LEUKEMIA CELLS BY MAB THERAPY
通过 MAB 疗法根除急性粒细胞白血病细胞
- 批准号:
3889304 - 财政年份:
- 资助金额:
$ 32.37万 - 项目类别: