权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
9193069
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
项目类别：
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/9193069
关键词：
Address Affect Attenuated Behavior Behavioral Brain Breast Cancer Model Cancer Etiology Cancer Intervention 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 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 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 mouse model neurobehavioral neuroinflammation novel physical conditioning protein expression public health relevance relating to nervous system standardize measure tool tumor tumor growth

项目摘要

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-κB, 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（由申请人提供）：关于先前癌症经历对大脑和行为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中枢神经系统以外的癌症如何影响大脑生理学，从而影响癌症期间和癌症成功解决后的大脑功能。作为我们实现长期目标的第一步，该R 03项目的总体目标是为随后的NCI R 01申请收集初步数据，并通过创建肿瘤切除的“幸存者”小鼠模型，开发已建立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诱导小胶质细胞介导的神经炎症并损害学习和记忆，这两者都可以通过肿瘤切除得到改善。提出了两个具体的目的来使用乳腺癌的非转移性小鼠模型和乳腺癌“存活”（即，完全肿瘤切除）。目的1是确定肿瘤发展和肿瘤切除后认知行为的改变。根据我们的初步数据，工作假设是外周肿瘤诱导特定的学习和记忆障碍，如标准化啮齿动物行为测试所测量的，而肿瘤切除可减弱这些障碍。目标2将确定与认知相关的神经改变，并与肿瘤生长或肿瘤切除术一致。这一目标的工作假设是外周肿瘤触发小胶质细胞介导的神经炎症（例如，促炎性细胞因子、NF-κB、吲哚胺-2，3-脱氧酶mRNA和蛋白表达的升高以及活化的小胶质细胞形态）与学习和记忆障碍一致。目标1的预期结局是识别仅受CNS外肿瘤影响或使用新肿瘤模型切除肿瘤后保留的特定类型或认知行为成分。目标2将为这些行为变化背后的机制神经通路提供基础。这一贡献将是重要的，因为它将为癌症和幸存者相关的认知问题提供神经炎症特异性干预靶点，这在人类研究中是不可能的。在我们看来，这项研究是创新的，因为它建立了一个乳腺癌生存模型，通过该模型来调查与迅速扩大的癌症幸存者人口相关的问题。这项拟议中的研究也是创新的，因为它将开始描绘癌症、癌症治疗和癌症相关压力在与癌症相关的认知变化中的作用。