|Grant Number:||5R01CA104825-05 Interpret this number|
|Primary Investigator:||Lutgendorf, Susan|
|Organization:||University Of Iowa|
|Project Title:||Biobehavioral-Cytokine Interactions in Ovarian Cancer|
DESCRIPTION (provided by applicant): Ovarian cancer is the second most common gynecologic cancer. Because of low rates of survival for the majority of ovarian cancer patients, identification of factors contributing to tumor growth and progression is of paramount importance. Although relationships between psychosocial factors and immunity have been extensively documented, there has been little investigation of relationships between psychosocial factors and cytokines involved in angiogenesis, the formation of new blood vessels that enhance tumor growth. These cytokines include Interleukin-8 (IL-8), Interleukin-12 (IL-12), Interleukin-6 (IL-6), and Vascular Endothelial Growth Factor (VEGF). VEGF, one of the key promoters of tumor angiogenesis, is associated with poorer ovarian cancer survival. VEGF is influenced by a variety of cytokines, hormones including cortisol, and by sympathetic activation. We have reported that ovarian cancer patients reporting greater social support had significantly lower serum VEGF pre-surgery, whereas those reporting greater feelings of distress had higher VEGF. Additionally, in an in vitro model, we have observed that stress hormones, such as norepinephrine, induce production of VEGF from an ovarian tumor cell line and that these tumor cells also express beta-adrenergic receptors. These effects are further augmented by cortisol. These novel findings, coupled with known hormonal modulation of other angiogenic cytokines, highlight the possibility that psychosocial factors may directly influence angiogenesis, and thus tumor progression in ovarian cancer. This 5-year prospective longitudinal study will investigate relationships among psychosocial factors and 4 angiogenic cytokines: VEGF, IL-6, IL-8, and IL-12, among 154 ovarian cancer patients in a clinical setting. We have selected these cytokines because of their critical role in ovarian cancer growth and progression. Measurements of cytokines and psychosocial factors will be taken pre-surgery and at intervals up to 9 months post-surgery; disease progression will be assessed until 18 months post-surgery. The significance of these findings is that they will investigate a novel mechanism by which biobehavioral factors in ovarian cancer patients may contribute to tumor growth and disease progression. Findings will have implications for innovative behavioral and pharmacological intervention strategies for ovarian cancer patients.
Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer.
Authors: Watkins JL, Thaker PH, Nick AM, Ramondetta LM, Kumar S, Urbauer DL, Matsuo K, Squires KC, Coleman RL, Lutgendorf SK, Ramirez PT, Sood AK
Source: Cancer, 2015 Aug 24;null, p. null.
EPub date: 2015 Aug 24.
Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.
Authors: Nagaraja AS, Dorniak PL, Sadaoui NC, Kang Y, Lin T, Armaiz-Pena G, Wu SY, Rupaimoole R, Allen JK, Gharpure KM, Pradeep S, Zand B, Previs RA, Hansen JM, Ivan C, Rodriguez-Aguayo C, Yang P, Lopez-Berestein G, Lutgendorf SK, Cole SW, Sood AK
Source: Oncogene, 2015 Aug 10;null, p. null.
EPub date: 2015 Aug 10.
Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer.
Authors: Davis LZ, Slavich GM, Thaker PH, Goodheart MJ, Bender DP, Dahmoush L, Farley DM, Markon KE, Penedo FJ, Lubaroff DM, Cole SW, Sood AK, Lutgendorf SK
Source: Cancer, 2015 Jun 10;null, p. null.
EPub date: 2015 Jun 10.
Biobehavioral and neuroendocrine correlates of antioxidant enzyme activity in ovarian carcinoma.
Authors: Bayer JL, Spitz DR, Christensen D, McCormick ML, Farley D, DeGeest K, Damoush L, Aust S, Sood AK, Lutgendorf SK
Source: Brain Behav Immun, 2015 May 16;null, p. null.
EPub date: 2015 May 16.
Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth.
Authors: Armaiz-Pena GN, Gonzalez-Villasana V, Nagaraja AS, Rodriguez-Aguayo C, Sadaoui NC, Stone RL, Matsuo K, Dalton HJ, Previs RA, Jennings NB, Dorniak P, Hansen JM, Arevalo JM, Cole SW, Lutgendorf SK, Sood AK, Lopez-Berestein G
Source: Oncotarget, 2015 Feb 28;6(6), p. 4266-73.
Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions.
Authors: Lutgendorf SK, Andersen BL
Source: Am Psychol, 2015 Feb-Mar;70(2), p. 186-97.
Diurnal cortisol and survival in epithelial ovarian cancer.
Authors: Schrepf A, Thaker PH, Goodheart MJ, Bender D, Slavich GM, Dahmoush L, Penedo F, DeGeest K, Mendez L, Lubaroff DM, Cole SW, Sood AK, Lutgendorf SK
Source: Psychoneuroendocrinology, 2015 Mar;53, p. 256-67.
EPub date: 2015 Jan 20.
Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer.
Authors: Stone RL, Baggerly KA, Armaiz-Pena GN, Kang Y, Sanguino AM, Thanapprapasr D, Dalton HJ, Bottsford-Miller J, Zand B, Akbani R, Diao L, Nick AM, DeGeest K, Lopez-Berestein G, Coleman RL, Lutgendorf S, Sood AK
Source: Cancer Biol Ther, 2014 Jul;15(7), p. 919-29.
EPub date: 2014 Apr 23.
Non-cancer life stressors contribute to impaired quality of life in ovarian cancer patients.
Authors: Lutgendorf SK, Slavich GM, Degeest K, Goodheart M, Bender D, Thaker PH, Penedo F, Zimmerman B, Lucci J 3rd, Mendez L, Collins K, Sood AK
Source: Gynecol Oncol, 2013 Dec;131(3), p. 667-73.
EPub date: 2013 Oct 3.
Sleep disturbance, distress, and quality of life in ovarian cancer patients during the first year after diagnosis.
Authors: Clevenger L, Schrepf A, Degeest K, Bender D, Goodheart M, Ahmed A, Dahmoush L, Penedo F, Lucci J 3rd, Thaker PH, Mendez L, Sood AK, Slavich GM, Lutgendorf SK
Source: Cancer, 2013 Sep 1;119(17), p. 3234-41.
EPub date: 2013 Jun 24.
Src activation by ?-adrenoreceptors is a key switch for tumour metastasis.
Authors: Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG, Han LY, Mangala LS, Villares GJ, Vivas-Mejia P, Rodriguez-Aguayo C, Nagaraja AS, Gharpure KM, Wu Z, English RD, Soman KV, Shahzad MM, Zigler M, Deavers MT, Zien A, Soldatos TG, Jackson DB, Wiktorowicz JE, Torres-Lugo M, Young T, De Geest K, Gallick GE, Bar-Eli M, Lopez-Berestein G, Cole SW, Lopez GE, Lutgendorf SK, Sood AK
Source: Nat Commun, 2013;4, p. 1403.
Why stress is BAD for cancer patients.
Authors: Nagaraja AS, Armaiz-Pena GN, Lutgendorf SK, Sood AK
Source: J Clin Invest, 2013 Feb;123(2), p. 558-60.
EPub date: 2013 Jan 25.
Psychoneuroimmunology and cancer: a decade of discovery, paradigm shifts, and methodological innovations.
Authors: Green McDonald P, O'Connell M, Lutgendorf SK
Source: Brain Behav Immun, 2013 Mar;30 Suppl, p. S1-9.
EPub date: 2013 Jan 16.
Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability.
Authors: Schrepf A, Clevenger L, Christensen D, DeGeest K, Bender D, Ahmed A, Goodheart MJ, Dahmoush L, Penedo F, Lucci JA 3rd, Ganjei-Azar P, Mendez L, Markon K, Lubaroff DM, Thaker PH, Slavich GM, Sood AK, Lutgendorf SK
Source: Brain Behav Immun, 2013 Mar;30 Suppl, p. S126-34.
EPub date: 2012 Aug 5.
Social influences on clinical outcomes of patients with ovarian cancer.
Authors: Lutgendorf SK, De Geest K, Bender D, Ahmed A, Goodheart MJ, Dahmoush L, Zimmerman MB, Penedo FJ, Lucci JA 3rd, Ganjei-Azar P, Thaker PH, Mendez L, Lubaroff DM, Slavich GM, Cole SW, Sood AK
Source: J Clin Oncol, 2012 Aug 10;30(23), p. 2885-90.
EPub date: 2012 Jul 16.
Neuroendocrine influences on cancer progression.
Authors: Armaiz-Pena GN, Cole SW, Lutgendorf SK, Sood AK
Source: Brain Behav Immun, 2013 Mar;30 Suppl, p. S19-25.
EPub date: 2012 Jun 21.
Sleep disturbance, cytokines, and fatigue in women with ovarian cancer.
Authors: Clevenger L, Schrepf A, Christensen D, DeGeest K, Bender D, Ahmed A, Goodheart MJ, Penedo F, Lubaroff DM, Sood AK, Lutgendorf SK
Source: Brain Behav Immun, 2012 Oct;26(7), p. 1037-44.
EPub date: 2012 Apr 21.
Paraneoplastic thrombocytosis in ovarian cancer.
Authors: Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, Rupairmoole R, Armaiz-Pena GN, Pecot CV, Coward J, Deavers MT, Vasquez HG, Urbauer D, Landen CN, Hu W, Gershenson H, Matsuo K, Shahzad MM, King ER, Tekedereli I, Ozpolat B, Ahn EH, Bond VK, Wang R, Drew AF, Gushiken F, Lamkin D, Collins K, DeGeest K, Lutgendorf SK, Chiu W, Lopez-Berestein G, Afshar-Kharghan V, Sood AK
Source: N Engl J Med, 2012 Feb 16;366(7), p. 610-8.
Biobehavioral factors and cancer progression: physiological pathways and mechanisms.
Authors: Lutgendorf SK, Sood AK
Source: Psychosom Med, 2011 Nov-Dec;73(9), p. 724-30.
EPub date: 2011 Oct 21.
Stress influences on anoikis.
Authors: Sood AK, Lutgendorf SK
Source: Cancer Prev Res (Phila), 2011 Apr;4(4), p. 481-5.
Cancer induces inflammation and depressive-like behavior in the mouse: modulation by social housing.
Authors: Lamkin DM, Lutgendorf SK, Lubaroff D, Sood AK, Beltz TG, Johnson AK
Source: Brain Behav Immun, 2011 Mar;25(3), p. 555-64.
EPub date: 2010 Dec 21.
Impact of stress on cancer metastasis.
Authors: Moreno-Smith M, Lutgendorf SK, Sood AK
Source: Future Oncol, 2010 Dec;6(12), p. 1863-81.
Biobehavioral influences on cancer progression.
Authors: Costanzo ES, Sood AK, Lutgendorf SK
Source: Immunol Allergy Clin North Am, 2011 Feb;31(1), p. 109-32.
Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients.
Authors: Lutgendorf SK, DeGeest K, Dahmoush L, Farley D, Penedo F, Bender D, Goodheart M, Buekers TE, Mendez L, Krueger G, Clevenger L, Lubaroff DM, Sood AK, Cole SW
Source: Brain Behav Immun, 2011 Feb;25(2), p. 250-5.
EPub date: 2010 Oct 16.