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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

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, 2014 Dec 30;null, p. null.
EPub date: 2014 Dec 30.
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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Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer.
Authors: Wen Y, Graybill WS, Previs RA, Hu W, Ivan C, Mangala LS, Zand B, Nick AM, Jennings NB, Dalton HJ, Sehgal V, Ram P, Lee JS, Vivas-Mejia PE, Coleman RL, Sood AK
Source: Clin Cancer Res, 2015 Jan 15;21(2), p. 448-59.
EPub date: 2014 Nov 21.
PMID: 25416196
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Molecular Pathways: Translational and Therapeutic Implications of the Notch Signaling Pathway in Cancer.
Authors: Previs RA, Coleman RL, Harris AL, Sood AK
Source: Clin Cancer Res, 2014 Nov 11;null, p. null.
EPub date: 2014 Nov 11.
PMID: 25388163
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Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression.
Authors: Rupaimoole R, Wu SY, Pradeep S, Ivan C, Pecot CV, Gharpure KM, Nagaraja AS, Armaiz-Pena GN, McGuire M, Zand B, Dalton HJ, Filant J, Miller JB, Lu C, Sadaoui NC, Mangala LS, Taylor M, van den Beucken T, Koch E, Rodriguez-Aguayo C, Huang L, Bar-Eli M, Wouters BG, Radovich M, Ivan M, Calin GA, Zhang W, Lopez-Berestein G, Sood AK
Source: Nat Commun, 2014 Oct 29;5, p. 5202.
EPub date: 2014 Oct 29.
PMID: 25351346
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Therapeutic silencing of KRAS using systemically delivered siRNAs.
Authors: Pecot CV, Wu SY, Bellister S, Filant J, Rupaimoole R, Hisamatsu T, Bhattacharya R, Maharaj A, Azam S, Rodriguez-Aguayo C, Nagaraja AS, Morelli MP, Gharpure KM, Waugh TA, Gonzalez-Villasana V, Zand B, Dalton HJ, Kopetz S, Lopez-Berestein G, Ellis LM, Sood AK
Source: Mol Cancer Ther, 2014 Dec;13(12), p. 2876-85.
EPub date: 2014 Oct 3.
PMID: 25281617
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Hematogenous metastasis of ovarian cancer: rethinking mode of spread.
Authors: Pradeep S, Kim SW, Wu SY, Nishimura M, Chaluvally-Raghavan P, Miyake T, Pecot CV, Kim SJ, Choi HJ, Bischoff FZ, Mayer JA, Huang L, Nick AM, Hall CS, Rodriguez-Aguayo C, Zand B, Dalton HJ, Arumugam T, Lee HJ, Han HD, Cho MS, Rupaimoole R, Mangala LS, Sehgal V, Oh SC, Liu J, Lee JS, Coleman RL, Ram P, Lopez-Berestein G, Fidler IJ, Sood AK
Source: Cancer Cell, 2014 Jul 14;26(1), p. 77-91.
PMID: 25026212
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Platelet effects on ovarian cancer.
Authors: Davis AN, Afshar-Kharghan V, Sood AK
Source: Semin Oncol, 2014 Jun;41(3), p. 378-84.
EPub date: 2014 Apr 23.
PMID: 25023353
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RNAi therapies: drugging the undruggable.
Authors: Wu SY, Lopez-Berestein G, Calin GA, Sood AK
Source: Sci Transl Med, 2014 Jun 11;6(240), p. 240ps7.
PMID: 24920658
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Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer.
Authors: Reusser NM, Dalton HJ, Pradeep S, Gonzalez-Villasana V, Jennings NB, Vasquez HG, Wen Y, Rupaimoole R, Nagaraja AS, Gharpure K, Miyake T, Huang J, Hu W, Lopez-Berestein G, Sood AK
Source: Cancer Biol Ther, 2014 Aug;15(8), p. 1061-7.
EPub date: 2014 May 19.
PMID: 24841852
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Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer.
Authors: Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, Armaiz-Pena G, Jiang D, Achreja A, Win J, Roopaimoole R, Rodriguez-Aguayo C, Mercado-Uribe I, Lopez-Berestein G, Liu J, Tsukamoto T, Sood AK, Ram PT, Nagrath D
Source: Mol Syst Biol, 2014 May 5;10, p. 728.
EPub date: 2014 May 5.
PMID: 24799285
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