Prostate Cancer Chemoprevention using a Natural Agent
使用天然药物化学预防前列腺癌
基本信息
- 批准号:8445062
- 负责人:
- 金额:$ 18.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-04-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAndrographisAnimalsAntibodiesApplications GrantsB-LymphocytesBiological AssayC57BL/6 MouseCancer PatientCell CountCell ProliferationCell SurvivalCell physiologyCell-Mediated CytolysisCellsChemopreventionChemopreventive AgentColorCytolysisCytoplasmic GranulesDataDendritic CellsDevelopmentDiseaseEffectivenessEnzyme-Linked Immunosorbent AssayFlow CytometryGrowthHost DefenseImageImmuneImmune responseImmune systemImmunohistochemistryImmunologic SurveillanceIn VitroIncidenceLuciferasesMalignant NeoplasmsMalignant neoplasm of prostateMature T-LymphocyteModelingMolecularMusNK Cell ActivationNatural Killer CellsNeoplasm MetastasisNeoplastic Cell TransformationOral AdministrationPTEN genePatientsPhenotypePreventionProductionProstatic NeoplasmsRecruitment ActivityRoleSerine ProteaseSerumSiteSystemT cell responseT-LymphocyteTestingToxic effectTranslatingTumor ImmunityTumor-Infiltrating Lymphocytesandrographolidebasebioluminescence imagingcancer cellcancer chemopreventionclinical applicationclinically relevantcytokinecytotoxicgranulysinin vivoinnovationinsightkillingslymphoblastmalemonocytemouse modelneoplastic cellnovelperforinprostate cancer cellprostate cancer modelprostate cancer preventionpublic health relevanceresearch studyrestorationtreatment strategytumortumor growthtumor progression
项目摘要
DESCRIPTION (provided by applicant): The long latency of prostate cancer (PCa) provides a window of opportunity for chemoprevention strategies. Most such strategies are focused on controling and/or reversing the mechanisms involved in neoplastic transformation and cancer progression. It is well accepted that, during development and progression, tumor cells evade the patient's defense system. In this regard, natural killer (NK) cells are cellular effectors of the innate immune system and are required for activation of the host defense system and for destruction of tumor cells. In PCa patients, however, the function of NK cells and their numbers are often compromised and/or depleted. Therefore, enhancing the function of NK cells by immunomodulatory compounds is a promising approach for PCa prevention. Recently, we demonstrated the immunomodulatory effects of andrographolide (AG), a natural compound isolated from Andrographis paniculata (AP), on NK cells and have established its antitumor effects in mice bearing PCa PTEN syngeneic tumors. Our preliminary results provide a rationale to investigate the function of AG in potentiating NK cells, which can act to eliminate PCa cells. Based on these encouraging preliminary data, we hypothesize that AG inhibits PCa growth by potentiating the anti-tumor activity of NK cells, thus offering an innovative, immune-based chemopreventive strategy for PCa. To test this hypothesis, we propose two specific aims. The first aim will use mouse models to determine the potential of AG in boosting NK cell activity against PCa. This will be achieved by establishing an interrelationship between the in vivo effects of AG through NK cel mobilization and cytotoxic activities and the effectiveness of AG in adaptive T cell responses through modulation of cytokine production by NK cells. In the second aim, we will establish the effects of AG on development, proliferation/survival, and cytotoxic function of NK cells. These studies, which will determine the effectiveness of AG in PCa chemoprevention achieved through boosting NK cell function, make the proposal clinically relevant and highly translational.
描述(由申请人提供):前列腺癌(PCa)的长潜伏期为化学预防策略提供了机会之窗。大多数此类策略集中于控制和/或逆转肿瘤转化和癌症进展中涉及的机制。众所周知,在发展和进展期间,肿瘤细胞逃避患者的防御系统。在这方面,自然杀伤(NK)细胞是先天免疫系统的细胞效应物,并且是激活宿主防御系统和破坏肿瘤细胞所需的。然而,在PCa患者中,NK细胞的功能和它们的数量通常受到损害和/或耗尽。因此,通过免疫调节化合物增强NK细胞的功能是预防PCa的有希望的方法。最近,我们证明了穿心莲(AG),从穿心莲(AP)中分离的天然化合物,对NK细胞的免疫调节作用,并建立了其在小鼠携带PCa PTEN同源肿瘤的抗肿瘤作用。我们的初步结果提供了一个理论基础,以调查AG在增强NK细胞,这可以消除PCa细胞的功能。基于这些令人鼓舞的初步数据,我们假设AG通过增强NK细胞的抗肿瘤活性来抑制PCa生长,从而为PCa提供了一种创新的基于免疫的化学预防策略。为了验证这一假设,我们提出了两个具体目标。第一个目标将使用小鼠模型来确定AG在增强NK细胞针对PCa的活性中的潜力。这将通过建立AG通过NK细胞动员和细胞毒性活性的体内作用与AG通过调节NK细胞产生的细胞因子在适应性T细胞应答中的有效性之间的相互关系来实现。在第二个目标中,我们将确定AG对NK细胞的发育、增殖/存活和细胞毒性功能的影响。这些研究将确定AG在通过增强NK细胞功能实现的PCa化学预防中的有效性,使该提案具有临床相关性和高度转化性。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Shailesh Singh其他文献
Shailesh Singh的其他文献
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{{ truncateString('Shailesh Singh', 18)}}的其他基金
Anti-CCL25 mAb to treat castration resistant prostate cancer
抗 CCL25 mAb 用于治疗去势抵抗性前列腺癌
- 批准号:
9264953 - 财政年份:2017
- 资助金额:
$ 18.47万 - 项目类别:
Anti-CXCL13 mAb to mitigate prostate cancer health disparities
抗 CXCL13 mAb 可减轻前列腺癌健康差异
- 批准号:
8998175 - 财政年份:2015
- 资助金额:
$ 18.47万 - 项目类别:
Role of chemokine receptor in disparities associated with prostate cancer progres
趋化因子受体在前列腺癌进展相关差异中的作用
- 批准号:
8918551 - 财政年份:2013
- 资助金额:
$ 18.47万 - 项目类别:
Role of chemokine receptor in disparities associated with prostate cancer progres
趋化因子受体在前列腺癌进展相关差异中的作用
- 批准号:
9340094 - 财政年份:2013
- 资助金额:
$ 18.47万 - 项目类别:
Role of chemokine receptor in disparities associated with prostate cancer progres
趋化因子受体在前列腺癌进展相关差异中的作用
- 批准号:
9137633 - 财政年份:2013
- 资助金额:
$ 18.47万 - 项目类别:
Role of chemokine receptor in disparities associated with prostate cancer progres
趋化因子受体在前列腺癌进展相关差异中的作用
- 批准号:
8585726 - 财政年份:2013
- 资助金额:
$ 18.47万 - 项目类别:
Role of chemokine receptor in disparities associated with prostate cancer progres
趋化因子受体在前列腺癌进展相关差异中的作用
- 批准号:
8728793 - 财政年份:2013
- 资助金额:
$ 18.47万 - 项目类别:
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