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Grant Details

Grant Number: 5R01CA109298-09 Interpret this number
Primary Investigator: Sood, Anil
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Ovarian Cancer: Mechanisms of Neuroendocrine Regulation
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): Ovarian cancer has the highest mortality rate among gynecologic malignancies. Due to poor survival of women with epithelial ovarian cancer, identification of factors responsible for accelerated cancer growth may have significance for clinical outcomes. Stress can elicit alterations of immunological, neurochemical, and endocrinological functions. While most of the research dealing with stress and accelerated tumor growth has focused on suppressed immunity, during our initial funding period we have uncovered new mechanisms by which chronic stress affects the tumor microenvironment. We established that sympathetic nervous system (SNS) activation in response to chronic stress resulted in increased production of pro- angiogenic factors by tumor cells. This increase was responsible for promoting tumor vascularity and perfusion. These effects were mediated by the 22-adrenergic receptors (ADRB2) on tumor cells and were blocked by beta-antagonists. However, there is third member of the catecholamine family, dopamine, which is known to have anti-angiogenic effects, but it is decreased in response to chronic stress. This project is designed to characterize dopamine levels in ovarian cancer using chronic stress models as well as human ovarian cancers. Furthermore, we will determine the expression levels of dopamine receptors in both ovarian cancer and endothelial cells. We will also analyze the biological effects of dopamine replacement using our well-characterized orthotopic model of ovarian carcinoma. Findings of this study could lead to identification of novel mechanisms underlying accelerated ovarian cancer growth and therefore may lead to new therapeutic approaches.

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Publications

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.
PMID: 26301456
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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.
PMID: 26257064
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Nanotechnology: Future of Oncotherapy.
Authors: Gharpure KM, Wu SY, Li C, Lopez-Berestein G, Sood AK
Source: Clin Cancer Res, 2015 Jul 15;21(14), p. 3121-30.
PMID: 26180057
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Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model.
Authors: Ravoori MK, Nishimura M, Singh SP, Lu C, Han L, Hobbs BP, Pradeep S, Choi HJ, Bankson JA, Sood AK, Kundra V
Source: PLoS One, 2015;10(6), p. e0131095.
EPub date: 2015 Jun 22.
PMID: 26098849
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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.
PMID: 25989110
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XPO1/CRM1 Inhibition Causes Antitumor Effects by Mitochondrial Accumulation of eIF5A.
Authors: Miyake T, Pradeep S, Wu SY, Rupaimoole R, Zand B, Wen Y, Gharpure KM, Nagaraja AS, Hu W, Cho MS, Dalton HJ, Previs RA, Taylor ML, Hisamatsu T, Kang Y, Liu T, Shacham S, McCauley D, Hawke DH, Wiktorowicz JE, Coleman RL, Sood AK
Source: Clin Cancer Res, 2015 Jul 15;21(14), p. 3286-97.
EPub date: 2015 Apr 15.
PMID: 25878333
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PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer.
Authors: Thanapprapasr D, Previs RA, Hu W, Ivan C, Armaiz-Pena GN, Dorniak PL, Hansen JM, Rupaimoole R, Huang J, Dalton HJ, Ali-Fehmi R, Coleman RL, Sood AK
Source: Mol Cancer Ther, 2015 Jun;14(6), p. 1466-75.
EPub date: 2015 Apr 1.
PMID: 25833835
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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.
PMID: 25738355
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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.
PMID: 25647344
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Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches.
Authors: Choi HJ, Armaiz Pena GN, Pradeep S, Cho MS, Coleman RL, Sood AK
Source: Cancer Metastasis Rev, 2015 Mar;34(1), p. 19-40.
PMID: 25544368
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New ways to successfully target tumor vasculature in ovarian cancer.
Authors: Yang X, Shen F, Hu W, Coleman RL, Sood AK
Source: Curr Opin Obstet Gynecol, 2015 Feb;27(1), p. 58-65.
PMID: 25502429
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Differential platelet levels affect response to taxane-based therapy in ovarian cancer.
Authors: Bottsford-Miller J, Choi HJ, Dalton HJ, Stone RL, Cho MS, Haemmerle M, Nick AM, Pradeep S, Zand B, Previs RA, Pecot CV, Crane EK, Hu W, Lutgendorf SK, Afshar-Kharghan V, Sood AK
Source: Clin Cancer Res, 2015 Feb 1;21(3), p. 602-10.
EPub date: 2014 Dec 3.
PMID: 25473001
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