The Psychoneuroimmunological Consequences of Cancer and Cancer Survivorship

癌症和癌症生存的心理神经免疫学后果

• 批准号: 9018997
• 负责人: LEAH M PYTER
• 金额: $ 7.7万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-09 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018997
• 关键词: Address; Affect; Attenuated; Behavior; Behavioral; Brain; Breast Cancer Model; Cancer Etiology; Cancer Model; Cancer Survivor; Cancer Survivorship; Carcinogens; Central Nervous System Neoplasms; Chronic; Clinical; Cognition; Cognitive; Comorbidity; Data; Development; Disease; Excision; Foundations; Future; Goals; Harvest; Hospital Costs; Human; Immunocompetent; Impaired cognition; Impairment; Inflammatory; Intervention; Learning; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Measures; Mediating; Memory; Memory impairment; Mental Health; Mentorship; Messenger RNA; Methodology; Modeling; Morphology; Mus; Neural Pathways; Neurobiology; Neurosciences; Ohio; Outcome; Pathway interactions; Patients; Peripheral; Physiological; Physiology; Population; Primary Neoplasm; Psyche structure; Psychoneuroimmunology; Public Health; Publishing; Qualifying; Quality of life; Rattus; Research; Resected; Resolution; Resources; Rodent; Role; Scientist; Stress; Survivors; Symptoms; Techniques; Testing; Time; Universities; Work; anticancer research; base; behavior influence; behavior test; brain behavior; breast cancer survival; cancer survival; cancer therapy; cognitive change; cognitive performance; collaborative environment; cytokine; effective therapy; experience; human subject; improved; indolamine; innovation; insight; mRNA Expression; malignant breast neoplasm; mouse model; neurobehavioral; neuroinflammation; novel; physical conditioning; protein expression; public health relevance; relating to nervous system; standardize measure; tool; tumor; tumor growth

 DESCRIPTION (provided by applicant): Little is known about the duration, causes, or mechanisms underlying the enduring and prevalent consequences of a previous cancer experience on the brain and behavior. The long-term goal for this work is to determine how cancer outside of the CNS affects brain physiology and, therefore, brain function, both during cancer and after successful cancer resolution. The overall objective of this R03 project, as the first step in pursuit of our long-term goal, is to harvest preliminary data for the succeeding NCI R01 application and to develop an innovative extension of established tumor model methodology by creating a tumor resected "survivor" mouse mod- el. The central hypothesis for this project is that mouse mammary tumors induce microglial-mediated neuroinflammation and impair learning and memory, both of which are ameliorated by tumor resection. Two specific aims are proposed to test the central hypothesis using a non-metastatic mouse model of breast cancer and breast cancer "survival" (i.e., complete tumor resection). Aim 1 is to identify alterations in cognitive behavior during tumor development and post-tumor resection. Based on our preliminary data, the working hypothesis is that peripheral tumors induce specific learning and memory impairments as measured by standardized rodent behavioral tests, whereas tumor resection attenuates these impairments. Aim 2 will determine neural alterations relevant to cognition and coincident with tumor growth or following tumor resection. The working hypothesis for this aim is that peripheral tumors trigger microglial-mediated neuroinflammation (e.g., elevations in pro- inflammatory cytokines, NF-B, indolamine-2,3-deoxygenase mRNA and protein expression and activated microglial morphology) coincident with learning and memory impairments. The expected outcome for Aim 1 is the identification of specific types or components of cognitive behavior that are influenced solely by the presence of an extra-CNS tumor or which remain after tumor resection using a new tumor model. Aim 2 will provide the foundation for the mechanistic neural pathways underlying these behavioral changes. This contribution will be significant because it will provide insight into neuroinflammation-specific targets of intervention for cancer- and survivor-associated cognitive problems, which is not possible with human research. The proposed research is innovative, in our opinion, because it establishes a model of mammary cancer survivorship by which to investigate questions relevant to the rapidly expanding population of cancer survivors. The proposed research is also innovative because it will begin to delineate the roles of cancer, cancer treatment, and cancer-associated stress in cognitive changes related to cancer.

 描述（由适用提供）：关于以前癌症在大脑和行为上经历的持久和普遍后果的持续时间，原因或机制知之甚少。这项工作的长期目标是确定癌症之外的癌症在癌症和成功解决癌症后如何影响脑生理，因此，脑功能。作为追求我们的长期目标的第一步，该R03项目的总体目标是为依次的NCI R01应用收集初步数据，并通过创建切除的“幸存者”小鼠Mod-El来开发已建立的肿瘤模型方法的创新扩展。该项目的中心假设是小鼠乳腺肿瘤会诱导小胶质细胞介导的神经炎症和损害学习和记忆，这两者都通过肿瘤切除来改善。提出了两个具体目的，用于使用非转移性小鼠乳腺癌和乳腺癌“生存”（即完全肿瘤切除）测试中心假设。目的1是确定肿瘤发育和肿瘤切除后认知行为的改变。基于我们的初步数据，工作假设是外周肿瘤会诱导通过标准化啮齿动物行为测试来衡量的特定学习和记忆障碍，而肿瘤切除会减轻这些障碍。 AIM 2将确定与认知有关的神经改变，并与肿瘤生长或肿瘤切除后一致。此目的的工作假设是，外围肿瘤会引发小胶质细胞介导的神经炎症（例如，促炎性细胞因子，NF-B，吲哚胺-2,3-脱氧酶mRNA和蛋白质表达和蛋白质表达以及活化的小胶质细胞形态的升高）与学习和记忆力不一致。 AIM 1的预期结果是鉴定仅受外部CNS肿瘤的存在或使用新肿瘤模型后保留在肿瘤切除后的特定类型或成分。 AIM 2将为这些行为变化的基础提供基础。这项贡献将是重要的，因为它将提供对癌症和幸存者相关的认知问题的神经炎症特异性靶标的见解，这对于人类的研究是不可能的。在我们看来，拟议的研究具有创新性，因为它建立了乳腺癌生存模型，通过该模型调查与迅速扩大癌症生存人群相关的问题。拟议的研究也具有创新性，因为它将开始描述与癌症有关的认知变化中癌症，癌症治疗和相关压力的作用。