- Email: [email protected]
4. Stress management effects on biobehavioral processes in breast cancer
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Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64
the three astrocyte cell lines; CXCL-1 was induced in C8-D1A, C8D30, and bEnd.3. In the EOC2 cell line, iNos, IL-1beta, TNF-alpha, and MCP-1 were constitutively expressed and were not induced by IL-1 stimulation. These results suggest that IL-1 induces distinct gene expression patterns in different cell types of the CNS. doi:10.1016/j.bbi.2009.06.008
4. Stress management effects on biobehavioral processes in breast cancer M.H. Antoni 5665 Ponce DeLeon Blvd., Department of Psychology, University of Miami, Coral Gables, FL 33124, United States Sylvester Cancer Center, United States We used a stress management paradigm to illuminate biobehavioral processes underlying health outcomes in women undergoing treatment for breast cancer (BCa). A cognitive behavioral stress management (CBSM) intervention was designed to modulate psychosocial processes using relaxation/anxiety reduction, cognitive restructuring, coping effectiveness training, and interpersonal skills in a supportive group to improve psychosocial adaptation, and examine parallel changes in biobehavioral parameters that could explain health benefits. Two randomized controlled trials recruited women <8 weeks after surgery before beginning adjuvant therapy for Stages I–III BCa. Women assigned to CBSM revealed improvements in psychosocial adaptation (positive and negative mood, quality of life, interpersonal disruption) and biobehavioral parameters (PM serum cortisol, lymphocyte proliferative response, and Th1 and Th2 cytokine production) at follow-up compared to controls. CBSM-specific (relaxation skills) and non-CBSM-specific (emotional expression) changes and number of intervention sessions attended related to magnitude of effects. A third study tested the efficacy of CBSM delivered later in medical treatment (3–12 months post-adjuvant therapy), and found similar effects. To address intervention mechanism and dose a fourth study experimentally separates CBSM processes in abbreviated form (5-week relaxation vs. 5-week CBT vs. 5-week health education) and tests effects on psychosocial adaptation, di-urnal cortisol regulation, and cytokine production. We are following these cohorts to examine whether biobehavioral processes modulated during CBSM predict quality of life and health outcomes at longer-term follow-up. doi:10.1016/j.bbi.2009.06.009
5. Molecular mechanisms of Src activation in chronic stressinduced cancer growth G.N. Armaiz-Pena a, G.J. Villares d, L.Y. Han a, Y.G. Lin a, A.M. Sanguino e, M.T. Deavers f, G.E. Gallick d, M. Bar-Eli d, G. Lopez-Berestein e, S.W. Cole b, S.K. Lutgendorf c, A.K. Sood a a
Department of Gynecologic Oncology, U.T. M.D. Anderson Cancer Center, Houston, United States b Division of Hematology–Oncology, Department of Medicine, University of California School of Medicine, Los Angeles, United States c Department of Psychology, University of Iowa, Iowa City, United States d Department of Cancer Biology, U.T. M.D. Anderson Cancer Center, United States e Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer Center, United States f Department of Pathology, U.T. M.D. Anderson Cancer Center, United States
Clinical studies demonstrate that chronic stress, depression and other behavioral factors can influence cancer progression. The underlying mechanisms, however, are not fully understood. In this study, we show that catecholamines activate Src in ovarian, breast, melanoma and prostate cancer cells. Treatment with different ADRB agonists and blockers determined that ADRB1/2 receptors are required for SrcY419 phosphorylation. Treatment with a cAMP or PKA agonist/antagonists demonstrated that cAMP/PKA signaling is required for NE-induced Src activation. The unexpected tyrosine phosphorylation via cAMP/PKA activation was found to be mediated by direct phosphorylation of SrcS17 following NE treatment. In Src / cells transiently expressing Src, NE caused SrcY419 phosphorylation, which was absent in the SrcS17 A (mutated) cells. Functionally, we demonstrate that catecholamine-induced Src activation promotes tumor cell migration and invasion. Furthermore, in orthotopic models of ovarian carcinoma, chronic stress resulted in increased Src activation and Src silencing blocked the stress induced increases in tumor growth. In patients with ovarian cancer, high pSrcY419 levels correlated with worse mean patient survival, increased depressive symptoms and high tumoral NE levels. Collectively, these findings demonstrate that Src activation is a critical step in stress-induced cancer growth. To our knowledge this work is the first to dissect the critical molecular link between Src activation and stress-mediated cancer growth, and ultimately provide a biologically plausible and potent way of inhibiting tumor progression among patients with cancer.
doi:10.1016/j.bbi.2009.06.010
6. Acute and long term adaptation of thyrotropin (TSH) and prolactin to restricted sleep and recovery J. Axelsson a, K. Brismar a, T. Akerstedt a,b, M. Lekander a a b
Karolinska Institutet, Stockholm, Sweden Stockholm University, Stockholm, Sweden
Disturbed sleep has recently been acknowledged as a major risk factor for a wide range of diseases. To obtain a better understanding of how disturbed sleep induces its harmful effects, we investigated how endocrine markers adapt to chronic sleep restriction and subsequent recovery. Nine subjects spent 12 days/nights in the sleep laboratory, three baseline days (sleep 23–07 h), five days with restricted sleep (03–07 h) and four recovery days (23–07 h). Blood was drawn 14 times/day during 9 days, and were analysed with respect to thyrotropin (thyroid stimulating hormone, TSH) and prolactin. The levels of TSH increased abruptly in response to acute sleep restriction, but decreased gradually with oncoming days with restricted sleep and were close to normal after five days with restricted sleep (p < .05). TSH levels were strongly reduced the first recovery day, but increased gradually the following days (p < .05). Sleep restriction had reversed effects on prolactin with an acute decrease the first nights with restricted sleep, but thereafter increased gradually (p < .05). Prolactin was further increased the first recovery day, but returned to baseline thereafter (p < .05). Both sleep restriction (4 h) and recovery sleep (8 h) hade strong acute effects on TSH and prolactin regulation. However, the strong acute effects were followed by a gradual adaptation to the new sleep pattern with levels returning to baseline. The adaptation seemed to be somewhat faster for prolactin than TSH. doi:10.1016/j.bbi.2009.06.011
Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64
the three astrocyte cell lines; CXCL-1 was induced in C8-D1A, C8D30, and bEnd.3. In the EOC2 cell line, iNos, IL-1beta, TNF-alpha, and MCP-1 were constitutively expressed and were not induced by IL-1 stimulation. These results suggest that IL-1 induces distinct gene expression patterns in different cell types of the CNS. doi:10.1016/j.bbi.2009.06.008
4. Stress management effects on biobehavioral processes in breast cancer M.H. Antoni 5665 Ponce DeLeon Blvd., Department of Psychology, University of Miami, Coral Gables, FL 33124, United States Sylvester Cancer Center, United States We used a stress management paradigm to illuminate biobehavioral processes underlying health outcomes in women undergoing treatment for breast cancer (BCa). A cognitive behavioral stress management (CBSM) intervention was designed to modulate psychosocial processes using relaxation/anxiety reduction, cognitive restructuring, coping effectiveness training, and interpersonal skills in a supportive group to improve psychosocial adaptation, and examine parallel changes in biobehavioral parameters that could explain health benefits. Two randomized controlled trials recruited women <8 weeks after surgery before beginning adjuvant therapy for Stages I–III BCa. Women assigned to CBSM revealed improvements in psychosocial adaptation (positive and negative mood, quality of life, interpersonal disruption) and biobehavioral parameters (PM serum cortisol, lymphocyte proliferative response, and Th1 and Th2 cytokine production) at follow-up compared to controls. CBSM-specific (relaxation skills) and non-CBSM-specific (emotional expression) changes and number of intervention sessions attended related to magnitude of effects. A third study tested the efficacy of CBSM delivered later in medical treatment (3–12 months post-adjuvant therapy), and found similar effects. To address intervention mechanism and dose a fourth study experimentally separates CBSM processes in abbreviated form (5-week relaxation vs. 5-week CBT vs. 5-week health education) and tests effects on psychosocial adaptation, di-urnal cortisol regulation, and cytokine production. We are following these cohorts to examine whether biobehavioral processes modulated during CBSM predict quality of life and health outcomes at longer-term follow-up. doi:10.1016/j.bbi.2009.06.009
5. Molecular mechanisms of Src activation in chronic stressinduced cancer growth G.N. Armaiz-Pena a, G.J. Villares d, L.Y. Han a, Y.G. Lin a, A.M. Sanguino e, M.T. Deavers f, G.E. Gallick d, M. Bar-Eli d, G. Lopez-Berestein e, S.W. Cole b, S.K. Lutgendorf c, A.K. Sood a a
Department of Gynecologic Oncology, U.T. M.D. Anderson Cancer Center, Houston, United States b Division of Hematology–Oncology, Department of Medicine, University of California School of Medicine, Los Angeles, United States c Department of Psychology, University of Iowa, Iowa City, United States d Department of Cancer Biology, U.T. M.D. Anderson Cancer Center, United States e Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer Center, United States f Department of Pathology, U.T. M.D. Anderson Cancer Center, United States
Clinical studies demonstrate that chronic stress, depression and other behavioral factors can influence cancer progression. The underlying mechanisms, however, are not fully understood. In this study, we show that catecholamines activate Src in ovarian, breast, melanoma and prostate cancer cells. Treatment with different ADRB agonists and blockers determined that ADRB1/2 receptors are required for SrcY419 phosphorylation. Treatment with a cAMP or PKA agonist/antagonists demonstrated that cAMP/PKA signaling is required for NE-induced Src activation. The unexpected tyrosine phosphorylation via cAMP/PKA activation was found to be mediated by direct phosphorylation of SrcS17 following NE treatment. In Src / cells transiently expressing Src, NE caused SrcY419 phosphorylation, which was absent in the SrcS17 A (mutated) cells. Functionally, we demonstrate that catecholamine-induced Src activation promotes tumor cell migration and invasion. Furthermore, in orthotopic models of ovarian carcinoma, chronic stress resulted in increased Src activation and Src silencing blocked the stress induced increases in tumor growth. In patients with ovarian cancer, high pSrcY419 levels correlated with worse mean patient survival, increased depressive symptoms and high tumoral NE levels. Collectively, these findings demonstrate that Src activation is a critical step in stress-induced cancer growth. To our knowledge this work is the first to dissect the critical molecular link between Src activation and stress-mediated cancer growth, and ultimately provide a biologically plausible and potent way of inhibiting tumor progression among patients with cancer.
doi:10.1016/j.bbi.2009.06.010
6. Acute and long term adaptation of thyrotropin (TSH) and prolactin to restricted sleep and recovery J. Axelsson a, K. Brismar a, T. Akerstedt a,b, M. Lekander a a b
Karolinska Institutet, Stockholm, Sweden Stockholm University, Stockholm, Sweden
Disturbed sleep has recently been acknowledged as a major risk factor for a wide range of diseases. To obtain a better understanding of how disturbed sleep induces its harmful effects, we investigated how endocrine markers adapt to chronic sleep restriction and subsequent recovery. Nine subjects spent 12 days/nights in the sleep laboratory, three baseline days (sleep 23–07 h), five days with restricted sleep (03–07 h) and four recovery days (23–07 h). Blood was drawn 14 times/day during 9 days, and were analysed with respect to thyrotropin (thyroid stimulating hormone, TSH) and prolactin. The levels of TSH increased abruptly in response to acute sleep restriction, but decreased gradually with oncoming days with restricted sleep and were close to normal after five days with restricted sleep (p < .05). TSH levels were strongly reduced the first recovery day, but increased gradually the following days (p < .05). Sleep restriction had reversed effects on prolactin with an acute decrease the first nights with restricted sleep, but thereafter increased gradually (p < .05). Prolactin was further increased the first recovery day, but returned to baseline thereafter (p < .05). Both sleep restriction (4 h) and recovery sleep (8 h) hade strong acute effects on TSH and prolactin regulation. However, the strong acute effects were followed by a gradual adaptation to the new sleep pattern with levels returning to baseline. The adaptation seemed to be somewhat faster for prolactin than TSH. doi:10.1016/j.bbi.2009.06.011