Adrenergic modulation of ovarian cancer progression and chemoresistance

卵巢癌进展和化疗耐药的肾上腺素调节

• 批准号: 9419236
• 负责人: GUILLERMO N ARMAIZ-PENA
• 金额: $ 7.81万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9419236
• 关键词: Adenosine Monophosphate; Adrenergic Agents; Affect; Aftercare; Apoptosis; Attenuated; Automobile Driving; BRCA1 Protein; BRCA1 gene; Biological; Biology; Breast; CDKN1C gene; Cancer Biology; Cancer Center; Cancer Patient; Cancer cell line; Cancer-Predisposing Gene; Cardiovascular Pathology; Catecholamines; Cells; Chronic stress; Cisplatin; Clinical; Code; Cognitive Therapy; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclin-Dependent Kinase Inhibitor; DNA Damage; DNA Nucleotidylexotransferase; DNA Repair; Data; Depressed mood; Disease; Distress; Emotional; Epinephrine; Exhibits; Future; Gene Expression; Gene Targeting; Generations; Genes; Genomics; Goals; Growth; Health Sciences; Hormones; Infiltration; Inflammatory; Joints; Label; Lead; Link; Maintenance; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Messenger RNA; Nerve; Norepinephrine; Outcome; Ovarian; Ovarian Serous Adenocarcinoma; Pathway interactions; Patient Self-Report; Patients; Periodicity; Platinum; Regulation; Research; Resistance; Risk; Risk Factors; Role; Signal Transduction; Social support; Stress; Sympathetic Nervous System; Testing; Transcriptional Regulation; Tumor Biology; Tumor Initiators; Universities; Work; base; cancer biomarkers; cancer cell; chemotherapy; chronic depression; cytokine; depressive symptoms; experimental study; macrophage; malignant breast neoplasm; neoplastic cell; outcome forecast; precision medicine; protein expression; psychologic; psychosocial; response; social; symptomatology; transcriptome; tumor; tumor microenvironment; tumor progression

PROJECT SUMMARY/ABSTRACT There is growing evidence for the role of stress in cardiovascular pathologies, cancer, and other diseases. Work from our group and others has shown that psychological states such as chronic stress or depression may accelerate growth of existing tumors and promote chemoresistance. Importantly, a significant number of ovarian cancer patients are clinically depressed or lack social support. These emotional states have been linked to sustained activation of the sympathetic nervous system and decreased survival. Our group has shown that activation of the sympathetic nervous system leads to increased levels of norepinephrine and epinephrine in the tumor microenvironment and ovarian cancer progression by inducing pro-tumoral pathways. Our preliminary data in cancer cell lines suggest that norepinephrine significantly changes the expression of genes implicated in ovarian cancer and attenuates cisplatin-induced ovarian cancer cell apoptosis. Given the importance of BRCA1-regulated DNA repair mechanisms in cisplatin response, adrenergic regulation of BRCA1 expression in tumors may also impact ovarian cancer progression and resistance to platinum-based therapy. However, the underlying mechanisms behind these observations are not completely understood. In this pilot we will test this hypothesis by achieving the following aims: 1) To dissect the effects of adrenergic signaling in ovarian cancer cells and 2) To explore the association between perceived stress and depressive symptomatology with tumor catecholamines, DNA damage, and BRCA1 protein expression. This proposal provides a unique approach to explore the link between stress and ovarian cancer outcomes at both the tumor level and the patient level. This proposal will provide the groundwork for additional research on precision medicine by linking psychological risk factors with underlying tumor biology.

项目总结/文摘