Immune dysregulation by psychosocial distress
心理社会困扰导致的免疫失调
基本信息
- 批准号:8434283
- 负责人:
- 金额:$ 51.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-03-01 至 2015-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAffectAmericanAnxietyBinding SitesBiopsyBreastCancer ControlCancer EtiologyCancer PatientCell NucleusCell physiologyCellsCessation of lifeChromatinDNADNA BindingDevelopmentDiagnosisDistressEpigenetic ProcessEpithelialExhibitsFrightFutureGene ExpressionGenesGlucocorticoidsGrowthHistone AcetylationHistonesHydrocortisoneImmuneImmune System DiseasesImmune responseImmune systemIndividualInterferon Type IIInvestigationLeadLinkMalignant NeoplasmsMediatingMethodologyModelingModificationMolecularMononuclearNatural Killer CellsNeoplasm MetastasisNervous system structureNuclearPatientsPatternPeripheral Blood Mononuclear CellPhosphorylationPrimary NeoplasmProductionPromoter RegionsPsychoneuroimmunologyRecoveryReportingRepressionRiskSECTM1 geneScienceStagingStressSymptomsTechnologyTestingTimeTranscription Factor AP-1Treatment/Psychosocial EffectsUncertaintyWhole BloodWomanWorkbasebiological adaptation to stressbreast cancer diagnosiscancer diagnosischromatin immunoprecipitationcohortcytokinedesigndisturbance in affectemotional distressexperiencehypothalamic-pituitary-adrenal axisimmune functioninsightmalignant breast neoplasmnovel strategiesperforinperipheral bloodprospectiveprotective effectpsychobiologicpsychosocialpublic health relevanceresponsetranscription factortranslational studytumortumor growthtumor initiation
项目摘要
DESCRIPTION (provided by applicant): Breast cancer is the second leading cause of cancer death in American women. It is no surprise that women respond to a diagnosis of breast cancer with substantial psychosocial distress. Evidence from psychoneuroimmunology demonstrates that psychosocial distress impairs immune function by reducing natural killer cell activity (NKCA) and the production of interferon (IFN) gamma. Both NKCA and IFN gamma contribute to protection from tumor initiation, primary tumor growth, and tumor metastasis. Of note, epithelial tumors, like those of the breast, are responsive to NK cells and IFN gamma; hence, reductions in these forms of immune defense are relevant to breast cancer. We show that women diagnosed with breast cancer experience psychosocial distress, which is accompanied by elevated levels of cortisol, decreased NKCA, and reduced IFN gamma production. The purpose of this project is to determine whether epigenetic pattern underlies the mechanism for the immune dysregulation that occurs with a diagnosis of breast cancer. Aim 1 will longitudinally assess women diagnosed with early stage breast cancer and evaluate the trajectory of their psychosocial, cortisol, and immune response with respect to their peripheral blood mononuclear (PBMC) epigenetic pattern. In Aims 2 and 3, these relationships will be investigated at the cellular and molecular level. Aim 2 will determine whether PBMC epigenetic pattern is associated with changes in the cellular levels of IFN gamma and/or perforin, two key effector molecules in cancer control. Aim 3 will determine whether PBMC epigenetic pattern is associated with changes in chromatin accessibility for the promoter regions of IFN gamma and/or perforin. Lastly, Aim 4 will evaluate an explanatory model that posits mediated relationships among the psychobiological variables. Latent growth curve analysis will be used to identify and evaluate the trajectories of the study variables with regard to PBMC epigenetic pattern. This project will provide a mechanistic understanding of immune dysregulation, consequent to psychosocial distress, and has the potential to spur development of new approaches to identify and manage individuals at risk for psychosocial distress mediated immune dysregulation.
描述(申请人提供):乳腺癌是美国女性癌症死亡的第二大原因。毫不奇怪,女性在被诊断出患有乳腺癌时会表现出巨大的心理压力。来自心理神经免疫学的证据表明,心理社会困境通过降低自然杀伤细胞活性(NKCA)和干扰素(干扰素)γ的产生来损害免疫功能。NKCA和干扰素-γ都有助于防止肿瘤的发生、原发肿瘤的生长和肿瘤的转移。值得注意的是,像乳腺肿瘤一样,上皮性肿瘤对NK细胞和干扰素-γ有反应;因此,这些形式的免疫防御的减少与乳腺癌有关。我们发现,被诊断为乳腺癌的女性经历了心理社会痛苦,伴随着皮质醇水平的升高,NKCA的减少,以及干扰素-γ的产生。这个项目的目的是确定表观遗传模式是否是乳腺癌诊断中发生的免疫失调的机制的基础。目的1将纵向评估被诊断为早期乳腺癌的妇女,并评估她们的心理社会、皮质醇和免疫反应与其外周血单核细胞(PBMC)表观遗传模式的轨迹。在目标2和目标3中,这些关系将在细胞和分子水平上进行研究。目的2将确定PBMC表观遗传模式是否与细胞水平的变化有关,干扰素和/或穿孔素是癌症控制中的两个关键效应分子。目的3将确定PBMC表观遗传模式是否与干扰素-γ和/或穿孔素启动子区域染色质可及性的变化有关。最后,目标4将评估一个假定心理生物学变量之间存在中介关系的解释性模型。潜在生长曲线分析将被用来识别和评估与PBMC表观遗传模式相关的研究变量的轨迹。该项目将提供对心理社会痛苦导致的免疫失调的机械性理解,并有可能促进新方法的发展,以识别和管理处于心理社会困境介导的免疫失调风险的个人。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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Linda Janusek其他文献
Linda Janusek的其他文献
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{{ truncateString('Linda Janusek', 18)}}的其他基金
Chromatin organization as a predictor of stress induced immune dysregulation
染色质组织作为应激引起的免疫失调的预测因子
- 批准号:
9245665 - 财政年份:2016
- 资助金额:
$ 51.04万 - 项目类别:
Mindfulness Based Stress Reduction for Psycho-Immune Dysregulation in Cancer
基于正念的减压治疗癌症心理免疫失调
- 批准号:
7916531 - 财政年份:2009
- 资助金额:
$ 51.04万 - 项目类别:
Mindfulness Based Stress Reduction for Psycho-Immune Dysregulation in Cancer
基于正念的减压治疗癌症心理免疫失调
- 批准号:
7940227 - 财政年份:2009
- 资助金额:
$ 51.04万 - 项目类别:
Mindfulness Based Stress Reduction for Psycho-Immune Dysregulation in Cancer
基于正念的减压治疗癌症心理免疫失调
- 批准号:
8080873 - 财政年份:2008
- 资助金额:
$ 51.04万 - 项目类别:
Mindfulness Based Stress Reduction for Psycho-Immune Dysregulation in Cancer
基于正念的减压治疗癌症心理免疫失调
- 批准号:
8281711 - 财政年份:2008
- 资助金额:
$ 51.04万 - 项目类别:
Mindfulness Based Stress Reduction for Psycho-Immune Dysregulation in Cancer
基于正念的减压治疗癌症心理免疫失调
- 批准号:
7623101 - 财政年份:2008
- 资助金额:
$ 51.04万 - 项目类别:
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