MOLECULAR DETERMINANTS OF GEMCITABINE (Franklin Hays)
吉西他滨的分子决定因素 (Franklin Hays)
基本信息
- 批准号:9099947
- 负责人:
- 金额:$ 20.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至 2018-05-31
- 项目状态:已结题
- 来源:
- 关键词:5 fluorouridineAddressAdenocarcinomaAdverse effectsAmino Acid SequenceAntimetabolitesAntineoplastic AgentsAntisense DNABiological AssayBreastCancer cell lineCell LineCell SurvivalCellsChemotherapy-Oncologic ProcedureClinicalColorectalCombined Modality TherapyCrystallizationCrystallographyDataDetergentsDevelopmentDiagnosisDiseaseDrug EffluxDrug TransportDrug resistanceElementsEnvironmentExposure toFamilyGatekeepingGenesGoalsHumanIn VitroIndividualIntegral Membrane ProteinKnowledgeLarge Cell CarcinomaLifeLinkLiposomesMalignant NeoplasmsMalignant neoplasm of lungMediatingMembraneMembrane ProteinsMentorsMethodologyMicrofluidicsModelingMolecularMutateMutationNon-Small-Cell Lung CarcinomaNormal CellNucleoside TransporterNucleosidesOklahomaOligonucleotidesOncologistOutcomeOutcome StudyPatient-Focused OutcomesPatientsPeptide Sequence DeterminationPharmaceutical PreparationsPharmacotherapyPositioning AttributePropidium DiiodideProtein IsoformsProteinsPublishingRadioactiveRegulationResistanceResolutionSingle Nucleotide PolymorphismSquamous cell carcinomaStructural GenesStructureTestingTherapeuticTimeTreatment EfficacyUnited StatesUnresectableUridineVesicleVisionYeastsabsorptionanti-cancer therapeuticanticancer researchbasecancer cellcancer therapychemotherapycytotoxicdesigndrug efficacygemcitabinegemzarhuman tissueimprovedin vivoinsightkillingsknock-downmortalitymutantneoplastic cellnoveloverexpressionpersonalized medicineprotein expressionprotein functionproteoliposomesreconstitutionresearch studyresponsesolutestructural biologysuccessthree dimensional structureuptake
项目摘要
Systemic chemotherapy is one of the remaining avenues available to an oncologist treating unresectable non-small cell lung cancer (NSCLC). Unfortunately, NSCLC indicated anticancer therapeutics do not provide significant patient survival benefits and have toxic side effects. These drugs will extend the time-to-progression of metastatic disease by small margins yet do little to decrease NSCLC mortality. An underlying theme to the current proposal is that one can obtain significant improvements in NSCLC chemotherapy with a more detailed molecular understanding of drug disposition and response. To obtain this understanding we will use a combination of structural biology and functional assays to study a human integral membrane protein directly linked to gemcitabine uptake within normal and neoplastic cells. The equilibrative nucleoside transporter (hENT) family is broadly distributed in human tissues, is known to transport a wide array of nucleoside antimetabolites, and is directly linked to chemotherapeutic outcomes. Specific goals we seek to address in this proposal include (1) determine the structure of hENT at atomic resolution, (2) develop in vitro functional assays using purified protein, and (3) characterize hENT functional determinants using three human lung cancer cell lines. Outcomes from these studies will be tuned to determine the molecular basis by which hENT regulatoin and transport of therapeutics occus. The broad vision is that these novel molecular insights can be advanced to clinical outcomes that guide treatment decisions in nucleoside based drug treatment of NSCLC.
全身化疗是肿瘤学家治疗不可切除的非小细胞肺癌(NSCLC)的剩余途径之一。不幸的是,NSCLC适应症的抗癌治疗剂不提供显著的患者生存益处并且具有毒副作用。这些药物将延长转移性疾病的进展时间,但对降低NSCLC死亡率几乎没有作用。当前提案的一个基本主题是,通过对药物分布和反应的更详细的分子理解,可以显着改善非小细胞肺癌化疗。为了获得这种理解,我们将使用结构生物学和功能测定的组合来研究与正常细胞和肿瘤细胞内的吉西他滨摄取直接相关的人整合膜蛋白。平衡型核苷转运蛋白(hENT)家族广泛分布于人体组织中,已知可转运多种核苷类抗代谢物,并与化疗结果直接相关。我们在本提案中寻求解决的具体目标包括:(1)在原子分辨率下确定hENT的结构,(2)使用纯化的蛋白质开发体外功能测定,以及(3)使用三种人肺癌细胞系表征hENT功能决定簇。这些研究的结果将被调整,以确定hENT调节和治疗药物转运发生的分子基础。广泛的愿景是,这些新的分子见解可以推进到临床结果,指导基于核苷的药物治疗NSCLC的治疗决策。
项目成果
期刊论文数量(0)
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FRANKLIN Alan HAYS其他文献
FRANKLIN Alan HAYS的其他文献
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{{ truncateString('FRANKLIN Alan HAYS', 18)}}的其他基金
Deciphering ShcA-mediated ROS Production as a Novel Intervention Strategy in Diabetes Therapy
解读 ShcA 介导的 ROS 产生作为糖尿病治疗的新型干预策略
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9753262 - 财政年份:2016
- 资助金额:
$ 20.64万 - 项目类别:
Deciphering ShcA-mediated ROS Production as a Novel Intervention Strategy in Diabetes Therapy
解读 ShcA 介导的 ROS 产生作为糖尿病治疗的新型干预策略
- 批准号:
9349551 - 财政年份:2016
- 资助金额:
$ 20.64万 - 项目类别:
Deciphering ShcA-mediated ROS Production as a Novel Intervention Strategy in Diabetes Therapy
解读 ShcA 介导的 ROS 产生作为糖尿病治疗的新型干预策略
- 批准号:
9193886 - 财政年份:2016
- 资助金额:
$ 20.64万 - 项目类别:
MOLECULAR DETERMINANTS OF GEMCITABINE (Franklin Hays)
吉西他滨的分子决定因素 (Franklin Hays)
- 批准号:
8539821 - 财政年份:
- 资助金额:
$ 20.64万 - 项目类别:
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