|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.
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 1;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.
Host factors and cancer progression: biobehavioral signaling pathways and interventions.
Authors: Lutgendorf SK, Sood AK, Antoni MH
Source: J Clin Oncol, 2010 Sep 10;28(26), p. 4094-9.
EPub date: 2010 Jul 19.
Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer.
Authors: Weinrib AZ, Sephton SE, Degeest K, Penedo F, Bender D, Zimmerman B, Kirschbaum C, Sood AK, Lubaroff DM, Lutgendorf SK
Source: Cancer, 2010 Sep 15;116(18), p. 4410-9.
Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis.
Authors: Sood AK, Armaiz-Pena GN, Halder J, Nick AM, Stone RL, Hu W, Carroll AR, Spannuth WA, Deavers MT, Allen JK, Han LY, Kamat AA, Shahzad MM, McIntyre BW, Diaz-Montero CM, Jennings NB, Lin YG, Merritt WM, DeGeest K, Vivas-Mejia PE, Lopez-Berestein G, Schaller MD, Cole SW, Lutgendorf SK
Source: J Clin Invest, 2010 May;120(5), p. 1515-23.
EPub date: 2010 Apr 12.
Care of the caregiver: stress and dysregulation of inflammatory control in cancer caregivers.
Authors: Lutgendorf SK, Laudenslager ML
Source: J Clin Oncol, 2009 Jun 20;27(18), p. 2894-5.
EPub date: 2009 May 11.
Glucose as a prognostic factor in ovarian carcinoma.
Authors: Lamkin DM, Spitz DR, Shahzad MM, Zimmerman B, Lenihan DJ, Degeest K, Lubaroff DM, Shinn EH, Sood AK, Lutgendorf SK
Source: Cancer, 2009 Mar 1;115(5), p. 1021-7.