Impact of Vitamin D on the Chemopreventive Efficacy of Erlotinib against Oral Cancer
维生素 D 对厄洛替尼口腔癌化学预防效果的影响
基本信息
- 批准号:9257368
- 负责人:
- 金额:$ 42.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-07 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAnimalsBiologyCalcitriolCancer PatientCarcinogen exposureCarcinogensCaspaseCell SurvivalChemopreventionChemopreventive AgentCholecalciferolClinical Trials DesignCritical PathwaysDevelopmentDietDietary SupplementationDihydroxycholecalciferolsDiseaseDown-RegulationDysplasiaEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor Tyrosine Kinase InhibitorErlotinibEstheticsEventExhibitsFutureHead and neck structureHistologicIncidenceInvestigationKnowledgeLaboratoriesLesionMAP Kinase GeneMalignant - descriptorMalignant NeoplasmsModelingMolecularMolecular AnalysisMucous MembraneMultimodal ImagingMusOral StagePathway interactionsPatientsPerfusionPhosphorylationPlayPremalignantPreventionPrevention strategyPrimary NeoplasmQuality of lifeReceptor InhibitionReceptor SignalingRecurrenceRegimenResearchRiskRoleSafetyScheduleSecondary PreventionSignal PathwaySignal TransductionTestingTherapeuticTumor AngiogenesisVitamin DVitamin D DeficiencyWorkXenograft ModelXenograft procedureangiogenesisbasecancer preventioncarcinogenesisclinical investigationclinical translationdietary supplementsexperimental studyin vivointerestmalignant mouth neoplasmmouth squamous cell carcinomaneoplasticnon-invasive imagingnovelnovel strategiesoral cancer preventionoral carcinogenesispre-clinicalpreclinical trialpreventpublic health relevancereceptorresearch clinical testingresponsetertiary preventiontumortumor growth
项目摘要
DESCRIPTION (provided by applicant): Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, there has been increased interest in targeting EGFR for chemoprevention. However, given the redundancy in molecular signaling of tumors, it is unlikely that inhibition of EGFR signaling alone would inhibit
malignant progression of OSCC. In this regard, natural compounds or nutritional supplements with favorable safety profiles are particularly attractive for use as potential 'bio-adjuvants' for
cancer prevention. To this end, our novel approach involves the use of the nutritional supplement, Vitamin D3 (or its active metabolite calcitriol) as a bio-adjuvant to enhance the chemopreventive efficacy of the EGFR inhibitor, Erlotinib. Two of the main downstream effects of the EGFR pathway involve activation of the MAPK- Erk and the PI3K-Akt pathways that are critically involved in cell survival, proliferation and angiogenesis. Calcitriol induces cleavage o MEK in a caspase-dependent manner and also decreases phosphorylation of Erk and Akt, that is necessary for their activation. It is therefore our hypothesis that targeting these interacting signaling pathways with calcitriol (or vitamin D) in combination with Erlotinib will be more effective in preventing oral cancer. The focus of the present work is to conduct a comprehensive preclinical investigation into the chemopreventive potential of this mechanistically-driven against
oral cancer. Using carcinogen and PDX models, the proposed research plan will evaluate the chemopreventive efficacy (Aim 1 and 2) and dissect the molecular mechanisms (Aim 3) involved in the response of oral cancers to this combination regimen. Positive results would pave the way for use of vitamin D3 in combination with Erlotinib for the prevention of oral cancer.
描述(由申请人提供):表皮生长因子受体(EGFR)途径的激活是头颈部癌症发生的早期事件。因此,人们越来越有兴趣将EGFR作为化学预防的靶点。然而,考虑到肿瘤分子信号的冗余性,仅抑制EGFR信号不太可能抑制
口腔鳞癌的恶性进展。在这方面,具有良好安全性的天然化合物或营养补充剂尤其具有吸引力,可用作潜在的
癌症预防。为此,我们的新方法涉及使用营养补充剂维生素D3(或其活性代谢物骨化三醇)作为生物佐剂,以增强EGFR抑制剂Erlotinib的化学预防效果。EGFR通路的两个主要下游效应涉及MAPK-Erk和PI3K-Akt通路的激活,这两个通路在细胞生存、增殖和血管生成中起关键作用。骨化三醇以caspase依赖的方式诱导MEK的裂解,并降低ERK和Akt的磷酸化,这是激活ERK和Akt所必需的。因此,我们的假设是,以骨化三醇(或维生素D)与厄洛替尼联合作用于这些相互作用的信号通路将在预防口腔癌方面更有效。目前的工作重点是对这种机械驱动的抗病毒药物的化学预防潜力进行全面的临床前调查。
口腔癌。利用致癌物和PDX模型,拟议的研究计划将评估化学预防效果(目标1和2),并剖析口腔癌对这种联合方案反应的分子机制(目标3)。阳性结果将为联合使用维生素D3和厄洛替尼预防口腔癌铺平道路。
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 }}
Mukund Seshadri其他文献
Mukund Seshadri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('Mukund Seshadri', 18)}}的其他基金
Radiation-induced Salivary Gland Vascular Injury: Mechanisms and Interventions
辐射引起的唾液腺血管损伤:机制和干预措施
- 批准号:
10701306 - 财政年份:2022
- 资助金额:
$ 42.88万 - 项目类别:
Acquisition of a 7T MR scanner for Translational Imaging Research at Roswell Park
购买一台 7T MR 扫描仪用于罗斯威尔公园的转化成像研究
- 批准号:
10176803 - 财政年份:2021
- 资助金额:
$ 42.88万 - 项目类别:
Radiogenomic Credentialing of Head and Neck Cancer Models
头颈癌模型的放射基因组学认证
- 批准号:
10529301 - 财政年份:2020
- 资助金额:
$ 42.88万 - 项目类别:
Radiogenomic Credentialing of Head and Neck Cancer Models
头颈癌模型的放射基因组学认证
- 批准号:
10310511 - 财政年份:2020
- 资助金额:
$ 42.88万 - 项目类别:
Non-invasive assessment of salivary gland function: Translational Studies
唾液腺功能的无创评估:转化研究
- 批准号:
9082643 - 财政年份:2016
- 资助金额:
$ 42.88万 - 项目类别:
Impact of Vitamin D on the Chemopreventive Efficacy of Erlotinib against Oral Cancer
维生素 D 对厄洛替尼口腔癌化学预防效果的影响
- 批准号:
10215646 - 财政年份:2016
- 资助金额:
$ 42.88万 - 项目类别:
Photoacoustic Micro-Imaging system for Shared Tumor Imaging Resource at Roswell P
Roswell P 共享肿瘤成像资源的光声微成像系统
- 批准号:
8247498 - 财政年份:2012
- 资助金额:
$ 42.88万 - 项目类别:
DEVELOPMENT AND VALIDATION OF AN IMAGING-BASED BIOMARKER OF THERAPEUTIC EFFICACY
基于成像的治疗效果生物标志物的开发和验证
- 批准号:
8089501 - 财政年份:2010
- 资助金额:
$ 42.88万 - 项目类别:
DEVELOPMENT AND VALIDATION OF AN IMAGING-BASED BIOMARKER OF THERAPEUTIC EFFICACY
基于成像的治疗效果生物标志物的开发和验证
- 批准号:
7990122 - 财政年份:2010
- 资助金额:
$ 42.88万 - 项目类别:
相似海外基金
Learning from animals how to regenerate: multidisciplinary training programme in regenerative biology
向动物学习如何再生:再生生物学的多学科培训计划
- 批准号:
EP/X030350/1 - 财政年份:2023
- 资助金额:
$ 42.88万 - 项目类别:
Research Grant
BIORETS: Research Experiences for Teachers in the Biology of Plants, Animals, Microorganisms, and their Environments
BIORETS:植物、动物、微生物及其环境生物学教师的研究经验
- 批准号:
2146882 - 财政年份:2022
- 资助金额:
$ 42.88万 - 项目类别:
Standard Grant
NSF Postdoctoral Fellowship in Biology FY 2019: Using herbarium specimens and animal movement data to assess when animals will help plants track niches in a changing climate
2019 财年 NSF 生物学博士后奖学金:利用植物标本和动物运动数据来评估动物何时帮助植物追踪气候变化中的生态位
- 批准号:
1907348 - 财政年份:2020
- 资助金额:
$ 42.88万 - 项目类别:
Fellowship Award
Visual system and cognitive biology in normal animals versus in an animal model of Alzheimer's disease with or without diabetes treated with solo or dual inflammasome inhibitors
正常动物的视觉系统和认知生物学与单独或双重炎性体抑制剂治疗的患有或不患有糖尿病的阿尔茨海默病动物模型的比较
- 批准号:
10712956 - 财政年份:2020
- 资助金额:
$ 42.88万 - 项目类别:
NSF Postdoctoral Fellowship in Biology FY 2019: Transfer of Antimicrobial Resistance Genes between Humans, Animals, and the Environment in urban Bangladesh
2019 财年 NSF 生物学博士后奖学金:孟加拉国城市人类、动物和环境之间抗菌素耐药性基因的转移
- 批准号:
1906957 - 财政年份:2019
- 资助金额:
$ 42.88万 - 项目类别:
Fellowship Award
Meeting: The -omics of chemical interactions in simple extant animals ; Society for Integrative and Comparative Biology, Tampa, Florida, January 3-7, 2019
会议:简单现存动物化学相互作用的组学;
- 批准号:
1831860 - 财政年份:2018
- 资助金额:
$ 42.88万 - 项目类别:
Standard Grant
EAPSI: Determining the Biology and Ecology of One of Earth's Earliest animals: Dickinsonia
EAPSI:确定地球上最早的动物之一:狄更逊水母的生物学和生态学
- 批准号:
1414911 - 财政年份:2014
- 资助金额:
$ 42.88万 - 项目类别:
Fellowship Award
Microbial Ecology and Theory of Animals Center for Excellence in Systems Biology
微生物生态学和动物理论系统生物学卓越中心
- 批准号:
8368096 - 财政年份:2012
- 资助金额:
$ 42.88万 - 项目类别:
The biology of personality in wild animals
野生动物人格的生物学
- 批准号:
261454-2008 - 财政年份:2012
- 资助金额:
$ 42.88万 - 项目类别:
Discovery Grants Program - Individual
Microbial Ecology and Theory of Animals Center for Excellence in Systems Biology
微生物生态学和动物理论系统生物学卓越中心
- 批准号:
9130832 - 财政年份:2012
- 资助金额:
$ 42.88万 - 项目类别: