Grant Details
Grant Number: |
5R01CA104825-05 Interpret this number |
Primary Investigator: |
Lutgendorf, Susan |
Organization: |
University Of Iowa |
Project Title: |
Biobehavioral-Cytokine Interactions in Ovarian Cancer |
Fiscal Year: |
2007 |
Abstract
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.
Publications
Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens.
Authors: Nagaraja A.S.
, Dood R.L.
, Armaiz-Pena G.
, Kang Y.
, Wu S.Y.
, Allen J.K.
, Jennings N.B.
, Mangala L.S.
, Pradeep S.
, Lyons Y.
, et al.
.
Source: Jci Insight, 2018-06-07 00:00:00.0; 3(11), .
EPub date: 2018-06-07 00:00:00.0.
PMID: 29889660
Related Citations
Sustained adrenergic signaling promotes intratumoral innervation through BDNF induction.
Authors: Allen J.K.
, Armaiz-Pena G.N.
, Nagaraja A.S.
, Sadaoui N.C.
, Ortiz T.
, Dood R.
, Ozcan M.
, Herder D.M.
, Haemerrle M.
, Gharpure K.M.
, et al.
.
Source: Cancer Research, 2018-04-16 00:00:00.0; , .
EPub date: 2018-04-16 00:00:00.0.
PMID: 29661830
Related Citations
Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer.
Authors: Cuneo M.G.
, Schrepf A.
, Slavich G.M.
, Thaker P.H.
, Goodheart M.
, Bender D.
, Cole S.W.
, Sood A.K.
, Lutgendorf S.K.
.
Source: Psychoneuroendocrinology, 2017 Oct; 84, p. 139-142.
EPub date: 2017-06-30 00:00:00.0.
PMID: 28711723
Related Citations
Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens.
Authors: Nagaraja A.S.
, Dood R.L.
, Armaiz-Pena G.
, Kang Y.
, Wu S.Y.
, Allen J.K.
, Jennings N.B.
, Mangala L.S.
, Pradeep S.
, Lyons Y.
, et al.
.
Source: Jci Insight, 2017-08-17 00:00:00.0; 2(16), .
EPub date: 2017-08-17 00:00:00.0.
PMID: 28814667
Related Citations
Changes in spiritual well-being and psychological outcomes in ovarian cancer survivors.
Authors: Davis L.Z.
, Cuneo M.
, Thaker P.H.
, Goodheart M.J.
, Bender D.
, Lutgendorf S.K.
.
Source: Psycho-oncology, 2017-06-21 00:00:00.0; , .
EPub date: 2017-06-21 00:00:00.0.
PMID: 28637083
Related Citations
SSRI use and clinical outcomes in epithelial ovarian cancer.
Authors: Christensen D.K.
, Armaiz-Pena G.N.
, Ramirez E.
, Matsuo K.
, Zimmerman B.
, Zand B.
, Shinn E.
, Goodheart M.J.
, Bender D.
, Thaker P.H.
, et al.
.
Source: Oncotarget, 2016-05-31 00:00:00.0; 7(22), p. 33179-91.
PMID: 27121207
Related Citations
Adrenergic Stimulation Of Dusp1 Impairs Chemotherapy Response In Ovarian Cancer
Authors: Kang Y.
, Nagaraja A.S.
, Armaiz-Pena G.N.
, Dorniak P.L.
, Hu W.
, Rupaimoole R.
, Liu T.
, Gharpure K.M.
, Previs R.A.
, Hansen J.M.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2016-04-01 00:00:00.0; 22(7), p. 1713-24.
PMID: 26581245
Related Citations
Biobehavioral And Neuroendocrine Correlates Of Antioxidant Enzyme Activity In Ovarian Carcinoma
Authors: Bayer J.L.
, Spitz D.R.
, Christensen D.
, McCormick M.L.
, Farley D.
, DeGeest K.
, Damoush L.
, Aust S.
, Sood A.K.
, Lutgendorf S.K.
.
Source: Brain, Behavior, And Immunity, 2015 Nov; 50, p. 58-62.
PMID: 25989110
Related Citations
Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer.
Authors: Davis L.Z.
, Slavich G.M.
, Thaker P.H.
, Goodheart M.J.
, Bender D.P.
, Dahmoush L.
, Farley D.M.
, Markon K.E.
, Penedo F.J.
, Lubaroff D.M.
, et al.
.
Source: Cancer, 2015-10-01 00:00:00.0; 121(19), p. 3543-50.
EPub date: 2015-10-01 00:00:00.0.
PMID: 26096769
Related Citations
Clinical Impact Of Selective And Nonselective Beta-blockers On Survival In Patients With Ovarian Cancer
Authors: Watkins J.L.
, Thaker P.H.
, Nick A.M.
, Ramondetta L.M.
, Kumar S.
, Urbauer D.L.
, Matsuo K.
, Squires K.C.
, Coleman R.L.
, Lutgendorf S.K.
, et al.
.
Source: Cancer, 2015-10-01 00:00:00.0; 121(19), p. 3444-51.
PMID: 26301456
Related Citations
Sympathetic Nervous System Regulation Of The Tumour Microenvironment
Authors: Cole S.W.
, Nagaraja A.S.
, Lutgendorf S.K.
, Green P.A.
, Sood A.K.
.
Source: Nature Reviews. Cancer, 2015 Sep; 15(9), p. 563-72.
PMID: 26299593
Related Citations
Sustained Adrenergic Signaling Leads To Increased Metastasis In Ovarian Cancer Via Increased Pge2 Synthesis
Authors: Nagaraja A.S.
, Dorniak P.L.
, Sadaoui N.C.
, Kang Y.
, Lin T.
, Armaiz-Pena G.
, Wu S.Y.
, Rupaimoole R.
, Allen J.K.
, Gharpure K.M.
, et al.
.
Source: Oncogene, 2015-08-10 00:00:00.0; , .
PMID: 26257064
Related Citations
Diurnal cortisol and survival in epithelial ovarian cancer.
Authors: Schrepf A.
, Thaker P.H.
, Goodheart M.J.
, Bender D.
, Slavich G.M.
, Dahmoush L.
, Penedo F.
, DeGeest K.
, Mendez L.
, Lubaroff D.M.
, et al.
.
Source: Psychoneuroendocrinology, 2015 Mar; 53, p. 256-67.
PMID: 25647344
Related Citations
Adrenergic Regulation Of Monocyte Chemotactic Protein 1 Leads To Enhanced Macrophage Recruitment And Ovarian Carcinoma Growth
Authors: Armaiz-Pena G.N.
, Gonzalez-Villasana V.
, Nagaraja A.S.
, Rodriguez-Aguayo C.
, Sadaoui N.C.
, Stone R.L.
, Matsuo K.
, Dalton H.J.
, Previs R.A.
, Jennings N.B.
, et al.
.
Source: Oncotarget, 2015-02-28 00:00:00.0; 6(6), p. 4266-73.
PMID: 25738355
Related Citations
Biobehavioral Approaches To Cancer Progression And Survival: Mechanisms And Interventions
Authors: Lutgendorf S.K.
, Andersen B.L.
.
Source: The American Psychologist, 2015 Feb-Mar; 70(2), p. 186-97.
PMID: 25730724
Related Citations
Focal Adhesion Kinase: An Alternative Focus For Anti-angiogenesis Therapy In Ovarian Cancer
Authors: Stone R.L.
, Baggerly K.A.
, Armaiz-Pena G.N.
, Kang Y.
, Sanguino A.M.
, Thanapprapasr D.
, Dalton H.J.
, Bottsford-Miller J.
, Zand B.
, Akbani R.
, et al.
.
Source: Cancer Biology & Therapy, 2014 Jul; 15(7), p. 919-29.
PMID: 24755674
Related Citations
From Childhood Trauma To Elevated C-reactive Protein In Adulthood: The Role Of Anxiety And Emotional Eating
Authors: Schrepf A.
, Markon K.
, Lutgendorf S.K.
.
Source: Psychosomatic Medicine, 2014 Jun; 76(5), p. 327-36.
PMID: 24933013
Related Citations
Non-cancer life stressors contribute to impaired quality of life in ovarian cancer patients.
Authors: Lutgendorf S.K.
, Slavich G.M.
, Degeest K.
, Goodheart M.
, Bender D.
, Thaker P.H.
, Penedo F.
, Zimmerman B.
, Lucci J.
, Mendez L.
, et al.
.
Source: Gynecologic Oncology, 2013 Dec; 131(3), p. 667-73.
PMID: 24096110
Related Citations
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.
, Thaker P.H.
, et al.
.
Source: Cancer, 2013-09-01 00:00:00.0; 119(17), p. 3234-41.
EPub date: 2013-09-01 00:00:00.0.
PMID: 23797955
Related Citations
Biologic Effects Of Dopamine On Tumor Vasculature In Ovarian Carcinoma
Authors: Moreno-Smith M.
, Lee S.J.
, Lu C.
, Nagaraja A.S.
, He G.
, Rupaimoole R.
, Han H.D.
, Jennings N.B.
, Roh J.W.
, Nishimura M.
, et al.
.
Source: Neoplasia (new York, N.y.), 2013 May; 15(5), p. 502-10.
PMID: 23633922
Related Citations
Neuroendocrine Influences On Cancer Progression
Authors: Armaiz-Pena G.N.
, Cole S.W.
, Lutgendorf S.K.
, Sood A.K.
.
Source: Brain, Behavior, And Immunity, 2013 Mar; 30 Suppl, p. S19-25.
PMID: 22728325
Related Citations
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 M.J.
, Dahmoush L.
, Penedo F.
, Lucci J.A.
, et al.
.
Source: Brain, Behavior, And Immunity, 2013 Mar; 30 Suppl, p. S126-34.
PMID: 22884960
Related Citations
Psychoneuroimmunology And Cancer: A Decade Of Discovery, Paradigm Shifts, And Methodological Innovations
Authors: Green McDonald P.
, O'Connell M.
, Lutgendorf S.K.
.
Source: Brain, Behavior, And Immunity, 2013 Mar; 30 Suppl, p. S1-9.
PMID: 23333846
Related Citations
Why Stress Is Bad For Cancer Patients
Authors: Nagaraja A.S.
, Armaiz-Pena G.N.
, Lutgendorf S.K.
, Sood A.K.
.
Source: The Journal Of Clinical Investigation, 2013 Feb; 123(2), p. 558-60.
PMID: 23348736
Related Citations
Src Activation By ¿-adrenoreceptors Is A Key Switch For Tumour Metastasis
Authors: Armaiz-Pena G.N.
, Allen J.K.
, Cruz A.
, Stone R.L.
, Nick A.M.
, Lin Y.G.
, Han L.Y.
, Mangala L.S.
, Villares G.J.
, Vivas-Mejia P.
, et al.
.
Source: Nature Communications, 2013; 4, p. 1403.
PMID: 23360994
Related Citations
Sleep disturbance, cytokines, and fatigue in women with ovarian cancer.
Authors: Clevenger L.
, Schrepf A.
, Christensen D.
, DeGeest K.
, Bender D.
, Ahmed A.
, Goodheart M.J.
, Penedo F.
, Lubaroff D.M.
, Sood A.K.
, et al.
.
Source: Brain, Behavior, And Immunity, 2012 Oct; 26(7), p. 1037-44.
PMID: 22543257
Related Citations
Social influences on clinical outcomes of patients with ovarian cancer.
Authors: Lutgendorf S.K.
, De Geest K.
, Bender D.
, Ahmed A.
, Goodheart M.J.
, Dahmoush L.
, Zimmerman M.B.
, Penedo F.J.
, Lucci J.A.
, Ganjei-Azar P.
, et al.
.
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2012-08-10 00:00:00.0; 30(23), p. 2885-90.
EPub date: 2012-08-10 00:00:00.0.
PMID: 22802321
Related Citations
Paraneoplastic Thrombocytosis In Ovarian Cancer
Authors: Stone R.L.
, Nick A.M.
, McNeish I.A.
, Balkwill F.
, Han H.D.
, Bottsford-Miller J.
, Rupairmoole R.
, Armaiz-Pena G.N.
, Pecot C.V.
, Coward J.
, et al.
.
Source: The New England Journal Of Medicine, 2012-02-16 00:00:00.0; 366(7), p. 610-8.
PMID: 22335738
Related Citations
Biobehavioral factors and cancer progression: physiological pathways and mechanisms.
Authors: Lutgendorf S.K.
, Sood A.K.
.
Source: Psychosomatic Medicine, 2011 Nov-Dec; 73(9), p. 724-30.
PMID: 22021459
Related Citations
Stress Influences On Anoikis
Authors: Sood A.K.
, Lutgendorf S.K.
.
Source: Cancer Prevention Research (philadelphia, Pa.), 2011 Apr; 4(4), p. 481-5.
PMID: 21464029
Related Citations
Cancer Induces Inflammation And Depressive-like Behavior In The Mouse: Modulation By Social Housing
Authors: Lamkin D.M.
, Lutgendorf S.K.
, Lubaroff D.
, Sood A.K.
, Beltz T.G.
, Johnson A.K.
.
Source: Brain, Behavior, And Immunity, 2011 Mar; 25(3), p. 555-64.
PMID: 21182930
Related Citations
Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients.
Authors: Lutgendorf S.K.
, DeGeest K.
, Dahmoush L.
, Farley D.
, Penedo F.
, Bender D.
, Goodheart M.
, Buekers T.E.
, Mendez L.
, Krueger G.
, et al.
.
Source: Brain, Behavior, And Immunity, 2011 Feb; 25(2), p. 250-5.
PMID: 20955777
Related Citations
Biobehavioral influences on cancer progression.
Authors: Costanzo E.S.
, Sood A.K.
, Lutgendorf S.K.
.
Source: Immunology And Allergy Clinics Of North America, 2011 Feb; 31(1), p. 109-32.
PMID: 21094927
Related Citations
Common-sense Beliefs About Cancer And Health Practices Among Women Completing Treatment For Breast Cancer
Authors: Costanzo,E.S.
, Lutgendorf,S.K.
, Roeder,S.L.
.
Source: Psycho-oncology, 2011 Jan; 20(1), p. 53-61.
PMID: 20148441
Related Citations
Impact Of Stress On Cancer Metastasis
Authors: Moreno-Smith M.
, Lutgendorf S.K.
, Sood A.K.
.
Source: Future Oncology (london, England), 2010 Dec; 6(12), p. 1863-81.
PMID: 21142861
Related Citations
Stress Effects On Fosb- And Interleukin-8 (il8)-driven Ovarian Cancer Growth And Metastasis
Authors: Shahzad M.M.
, Arevalo J.M.
, Armaiz-Pena G.N.
, Lu C.
, Stone R.L.
, Moreno-Smith M.
, Nishimura M.
, Lee J.W.
, Jennings N.B.
, Bottsford-Miller J.
, et al.
.
Source: The Journal Of Biological Chemistry, 2010-11-12 00:00:00.0; 285(46), p. 35462-70.
PMID: 20826776
Related Citations
Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer.
Authors: Weinrib A.Z.
, Sephton S.E.
, Degeest K.
, Penedo F.
, Bender D.
, Zimmerman B.
, Kirschbaum C.
, Sood A.K.
, Lubaroff D.M.
, Lutgendorf S.K.
.
Source: Cancer, 2010-09-15 00:00:00.0; 116(18), p. 4410-9.
PMID: 20564155
Related Citations
Host factors and cancer progression: biobehavioral signaling pathways and interventions.
Authors: Lutgendorf S.K.
, Sood A.K.
, Antoni M.H.
.
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2010-09-10 00:00:00.0; 28(26), p. 4094-9.
EPub date: 2010-09-10 00:00:00.0.
PMID: 20644093
Related Citations
Adrenergic Modulation Of Focal Adhesion Kinase Protects Human Ovarian Cancer Cells From Anoikis
Authors: Sood A.K.
, Armaiz-Pena G.N.
, Halder J.
, Nick A.M.
, Stone R.L.
, Hu W.
, Carroll A.R.
, Spannuth W.A.
, Deavers M.T.
, Allen J.K.
, et al.
.
Source: The Journal Of Clinical Investigation, 2010 May; 120(5), p. 1515-23.
PMID: 20389021
Related Citations
Computational Identification Of Gene-social Environment Interaction At The Human Il6 Locus
Authors: Cole S.W.
, Arevalo J.M.
, Takahashi R.
, Sloan E.K.
, Lutgendorf S.K.
, Sood A.K.
, Sheridan J.F.
, Seeman T.E.
.
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010-03-23 00:00:00.0; 107(12), p. 5681-6.
PMID: 20176930
Related Citations
Care of the caregiver: stress and dysregulation of inflammatory control in cancer caregivers.
Authors: Lutgendorf S.K.
, Laudenslager M.L.
.
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2009-06-20 00:00:00.0; 27(18), p. 2894-5.
EPub date: 2009-06-20 00:00:00.0.
PMID: 19433678
Related Citations
Surgical Stress Promotes Tumor Growth In Ovarian Carcinoma
Authors: Lee J.W.
, Shahzad M.M.
, Lin Y.G.
, Armaiz-Pena G.
, Mangala L.S.
, Han H.D.
, Kim H.S.
, Nam E.J.
, Jennings N.B.
, Halder J.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2009-04-15 00:00:00.0; 15(8), p. 2695-702.
PMID: 19351748
Related Citations
Glucose as a prognostic factor in ovarian carcinoma.
Authors: Lamkin D.M.
, Spitz D.R.
, Shahzad M.M.
, Zimmerman B.
, Lenihan D.J.
, Degeest K.
, Lubaroff D.M.
, Shinn E.H.
, Sood A.K.
, Lutgendorf S.K.
.
Source: Cancer, 2009-03-01 00:00:00.0; 115(5), p. 1021-7.
PMID: 19156916
Related Citations
Depression, social support, and beta-adrenergic transcription control in human ovarian cancer.
Authors: Lutgendorf S.K.
, DeGeest K.
, Sung C.Y.
, Arevalo J.M.
, Penedo F.
, Lucci J.
, Goodheart M.
, Lubaroff D.
, Farley D.M.
, Sood A.K.
, et al.
.
Source: Brain, Behavior, And Immunity, 2009 Feb; 23(2), p. 176-83.
PMID: 18550328
Related Citations
Neuroendocrine Modulation Of Cancer Progression
Authors: Armaiz-Pena G.N.
, Lutgendorf S.K.
, Cole S.W.
, Sood A.K.
.
Source: Brain, Behavior, And Immunity, 2009 Jan; 23(1), p. 10-5.
PMID: 18638541
Related Citations
Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma.
Authors: Lutgendorf S.K.
, Lamkin D.M.
, Jennings N.B.
, Arevalo J.M.
, Penedo F.
, DeGeest K.
, Langley R.R.
, Lucci J.A.
, Cole S.W.
, Lubaroff D.M.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2008-11-01 00:00:00.0; 14(21), p. 6839-46.
PMID: 18980978
Related Citations
Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients.
Authors: Lutgendorf S.K.
, Weinrib A.Z.
, Penedo F.
, Russell D.
, DeGeest K.
, Costanzo E.S.
, Henderson P.J.
, Sephton S.E.
, Rohleder N.
, Lucci J.A.
, et al.
.
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2008-10-10 00:00:00.0; 26(29), p. 4820-7.
EPub date: 2008-10-10 00:00:00.0.
PMID: 18779606
Related Citations
Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients.
Authors: Lutgendorf S.K.
, Lamkin D.M.
, DeGeest K.
, Anderson B.
, Dao M.
, McGinn S.
, Zimmerman B.
, Maiseri H.
, Sood A.K.
, Lubaroff D.M.
.
Source: Brain, Behavior, And Immunity, 2008 Aug; 22(6), p. 890-900.
PMID: 18276105
Related Citations
Neuroendocrine Influences On Cancer Biology
Authors: Thaker P.H.
, Sood A.K.
.
Source: Seminars In Cancer Biology, 2008 Jun; 18(3), p. 164-70.
PMID: 18201896
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Effect Of Interleukin-8 Gene Silencing With Liposome-encapsulated Small Interfering Rna On Ovarian Cancer Cell Growth
Authors: Merritt W.M.
, Lin Y.G.
, Spannuth W.A.
, Fletcher M.S.
, Kamat A.A.
, Han L.Y.
, Landen C.N.
, Jennings N.
, De Geest K.
, Langley R.R.
, et al.
.
Source: Journal Of The National Cancer Institute, 2008-03-05 00:00:00.0; 100(5), p. 359-72.
PMID: 18314475
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