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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

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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Molecular biomarkers of residual disease after surgical debulking of high-grade serous ovarian cancer.
Authors: Tucker SL, Gharpure K, Herbrich SM, Unruh AK, Nick AM, Crane EK, Coleman RL, Guenthoer J, Dalton HJ, Wu SY, Rupaimoole R, Lopez-Berestein G, Ozpolat B, Ivan C, Hu W, Baggerly KA, Sood AK
Source: Clin Cancer Res, 2014 Jun 15;20(12), p. 3280-8.
EPub date: 2014 Apr 22.
PMID: 24756370
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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.
PMID: 24755674
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Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer.
Authors: Gharpure KM, Chu KS, Bowerman CJ, Miyake T, Pradeep S, Mangala SL, Han HD, Rupaimoole R, Armaiz-Pena GN, Rahhal TB, Wu SY, Luft JC, Napier ME, Lopez-Berestein G, DeSimone JM, Sood AK
Source: Mol Cancer Ther, 2014 Jul;13(7), p. 1750-7.
EPub date: 2014 Apr 22.
PMID: 24755199
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Notch3 pathway alterations in ovarian cancer.
Authors: Hu W, Liu T, Ivan C, Sun Y, Huang J, Mangala LS, Miyake T, Dalton HJ, Pradeep S, Rupaimoole R, Previs RA, Han HD, Bottsford-Miller J, Zand B, Kang Y, Pecot CV, Nick AM, Wu SY, Lee JS, Sehgal V, Ram P, Liu J, Tucker SL, Lopez-Berestein G, Baggerly KA, Coleman RL, Sood AK
Source: Cancer Res, 2014 Jun 15;74(12), p. 3282-93.
EPub date: 2014 Apr 17.
PMID: 24743243
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Antagonism of tumoral prolactin receptor promotes autophagy-related cell death.
Authors: Wen Y, Zand B, Ozpolat B, Szczepanski MJ, Lu C, Yuca E, Carroll AR, Alpay N, Bartholomeusz C, Tekedereli I, Kang Y, Rupaimoole R, Pecot CV, Dalton HJ, Hernandez A, Lokshin A, Lutgendorf SK, Liu J, Hittelman WN, Chen WY, Lopez-Berestein G, Szajnik M, Ueno NT, Coleman RL, Sood AK
Source: Cell Rep, 2014 Apr 24;7(2), p. 488-500.
EPub date: 2014 Apr 3.
PMID: 24703838
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Biologic effects of platelet-derived growth factor receptor ? blockade in uterine cancer.
Authors: Roh JW, Huang J, Hu W, Yang X, Jennings NB, Sehgal V, Sohn BH, Han HD, Lee SJ, Thanapprapasr D, Bottsford-Miller J, Zand B, Dalton HJ, Previs RA, Davis AN, Matsuo K, Lee JS, Ram P, Coleman RL, Sood AK
Source: Clin Cancer Res, 2014 May 15;20(10), p. 2740-50.
EPub date: 2014 Mar 14.
PMID: 24634380
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2'-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity.
Authors: Wu SY, Yang X, Gharpure KM, Hatakeyama H, Egli M, McGuire MH, Nagaraja AS, Miyake TM, Rupaimoole R, Pecot CV, Taylor M, Pradeep S, Sierant M, Rodriguez-Aguayo C, Choi HJ, Previs RA, Armaiz-Pena GN, Huang L, Martinez C, Hassell T, Ivan C, Sehgal V, Singhania R, Han HD, Su C, Kim JH, Dalton HJ, Kovvali C, Keyomarsi K, McMillan NA, Overwijk WW, Liu J, Lee JS, Baggerly KA, Lopez-Berestein G, Ram PT, Nawrot B, Sood AK
Source: Nat Commun, 2014 Mar 12;5, p. 3459.
EPub date: 2014 Mar 12.
PMID: 24619206
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