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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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