The primary objective of this methodological supplement is to relate psychosocial self-reports to measurements of catecholamines extracted from ovarian tumor tissue, to enable examination of norepineprine (NE) and epinephrine (E) that is biologically available to these tumor cells and would likely contribute to their production of pro-angiogenic cytokines. The rationale for this is as follows. We have documented that ovarian cancer patients with low levels of social support have higher levels of vascular endothelial growth factor (VEGF), a cytokine that promotes angiogenesis (blood vessel growth in tumors). We have also experimentally demonstrated that both NE and E can induce increases in VEGF in ovarian cancer cell lines and that NE increases the invasive potential of ovarian cancer cells. We have documented the presence of beta-adrenergic receptors on ovarian tumor cell lines. These findings suggest that ovarian cancer would be a highly relevant model to study stress-catecholamine-angiogenesis relationships. Our working hypothesis is that stress hormones such as catecholamines can promote blood vessel growth in tumors by increasing the levels of proangiogenic cytokines. Dr. Lutgendorf is Principal Investigator on a 5 year RO1 grant entitled """"""""Biobehavioral Cytokine Interactions in Ovarian Cancer"""""""" (10/1/03-9/30/08) that prospectively examines relationships of psychosocial factors such as stress and social support to angiogenic cytokines and time to recurrence among ovarian cancer patients. It would be ideal in a project such as this to be able to measure stress hormones as possible mediators of the hypothesized effects on angiogenic cytokines of the psychosocial factors being measured by self-report. Pre-surgery, when subjects complete psychosocial surveys, there is no feasible way to measure peripheral catecholamines without inducing excessive patient burden. Furthermore it is not known what the catecholamine concentrations are in the microenvironment of the tumor. This proposal enables direct measurement within the tumor environment of the proposed endocrine mediators of the psychosocial factors measured by self-report. We will also measure these angiogenic mediators within the tumor. Thus with very little additional effort or expense, understanding of mechanisms underlying the hypothesized relationships between stress and tumor growth can be achieved, thus vastly enhancing the understanding that can be drawn from the parent grant. This proposal is responsive to the measurement aspect of the RFA in that it examines the assessment of the relationship of self-report measures to an innovative biological measure. To our knowledge, self-report psychosocial data has never been related to levels of catecholamines that are biologically available to tumor cells. Thus the measurement model we are proposing is highly innovative and could enhance methodology in biobehavioral studies in cancer control. ? ?
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