Harnessing the Multipotency of Cancer Stem Cells for Differentiation Therapy
利用癌症干细胞的多能性进行分化治疗
基本信息
- 批准号:8692120
- 负责人:
- 金额:$ 22.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-18 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:2,4-thiazolidinedioneAdipocytesAdolescentAffectAgonistAutomobile DrivingBenignBiological AssayCell LineageCell ProliferationCellsChildChildhoodClinicDevelopmentDiabetes MellitusDifferentiation TherapyDiseaseDrug usageFDA approvedFatty acid glycerol estersGenesGrowthHumanIncidenceInsulinLeadMalignant Bone NeoplasmMalignant NeoplasmsMesenchymalMesenchymal Cell NeoplasmMesenchymal Stem CellsMetastatic OsteosarcomaMusOperative Surgical ProceduresOsteoblastsOutcomePPAR gammaPathway interactionsPatientsPeroxisome Proliferator-Activated ReceptorsPharmaceutical PreparationsPhenotypePioglitazonePopulationProliferatingPropertyRecurrenceRecurrent diseaseRegimenRelapseResearchSafetyStagingStem cellsSurvival RateTeenagersTestingTherapeuticThiazolidinedionesTissuesTumor SuppressionTumorigenicityUndifferentiatedWorkalternative treatmentbasebonebone cellcancer cellcancer stem cellclinically significantimprovedlimb amputationlipid biosynthesisneoplastic cellnovelnovel strategiesnovel therapeuticsosteoprogenitor cellosteosarcomaoutcome forecastprogenitorpublic health relevancerosiglitazonestemstem cell differentiationtumortumor growthtumorigenic
项目摘要
DESCRIPTION (provided by applicant): Osteosarcoma is an aggressive bone cancer that affects children and adolescents. Osteosarcoma is considered a disease of disrupted differentiation wherein tumor cells are unable to differentiate into proper bone-forming mature osteoblasts. Osteosarcoma is often advanced at presentation and current treatments consist primarily of chemotherapeutic regimens and surgery. Osteosarcoma has a high rate of recurrence and often leads to limb amputations in young patients. The survival rate for metastatic osteosarcoma remains around 30% and alternative treatments are badly needed for this devastating disease. In this collaborative study, we propose to test a novel approach for treating osteosarcoma by harnessing intrinsic multipotency features of the osteosarcoma cancer stem cells. Osteosarcomas arise from mesenchymal stem cells that normally have the ability to form bone and fat cells. Our differentiation therapy approach is to use agents that preferentially inhibit the growth of osteosarcoma cancer stem cells while steering them to become adipocytes. We will use a class of drugs, the TZDs, that are agonists for PPAR?, the master regulator of adipogenesis. Several TZDs are approved for their unrelated effect in insulin clearance and treatment of diabetes. We have found that TZDs can inhibit the growth of osteosarcoma cells and promote adipogenic differentiation. We will test the effects of TZD on primary mouse and human osteosarcoma cells in mice, and examine their effects on cells and tumors. In particular, we will determine whether the TZDs can activate genes needed for adipogenesis. If successful, this proposal will provide the basis for new strategies to treat osteosarcoma in the clinic.
描述(由申请人提供):骨肉瘤是一种侵袭性骨癌,影响儿童和青少年。骨肉瘤被认为是一种分化破坏的疾病,其中肿瘤细胞无法分化成适当的骨形成成熟成骨细胞。骨肉瘤就诊时通常已是晚期,目前的治疗主要包括化疗方案和手术。骨肉瘤复发率很高,经常导致年轻患者截肢。转移性骨肉瘤的生存率仍然在 30% 左右,这种毁灭性疾病急需替代治疗。 在这项合作研究中,我们建议通过利用骨肉瘤癌症干细胞的内在多能性特征来测试一种治疗骨肉瘤的新方法。骨肉瘤由间充质干细胞产生,通常具有形成骨和脂肪细胞的能力。我们的分化治疗方法是使用优先抑制骨肉瘤癌症干细胞生长同时引导它们变成脂肪细胞的药物。 我们将使用一类药物,即 TZD,它们是 PPAR(脂肪生成的主要调节剂)的激动剂。几种 TZD 因其在胰岛素清除和糖尿病治疗方面的不相关作用而被批准。我们发现TZDs可以抑制骨肉瘤细胞的生长并促进成脂分化。我们将测试TZD对小鼠原代和人骨肉瘤细胞的影响,并检查其对细胞和肿瘤的影响。特别是,我们将确定 TZD 是否可以激活脂肪生成所需的基因。如果成功,该提案将为临床治疗骨肉瘤的新策略提供基础。
项目成果
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Alka Mansukhani其他文献
Alka Mansukhani的其他文献
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{{ truncateString('Alka Mansukhani', 18)}}的其他基金
Harnessing the Multipotency of Cancer Stem Cells for Differentiation Therapy
利用癌症干细胞的多能性进行分化治疗
- 批准号:
8929179 - 财政年份:2014
- 资助金额:
$ 22.12万 - 项目类别:
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