|Grant Number:||5R01CA109298-09 Interpret this number|
|Primary Investigator:||Sood, Anil|
|Organization:||Ut Md Anderson Cancer Ctr|
|Project Title:||Ovarian Cancer: Mechanisms of Neuroendocrine Regulation|
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.
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.
Monocyte subpopulations in angiogenesis.
Authors: Dalton HJ, Armaiz-Pena GN, Gonzalez-Villasana V, Lopez-Berestein G, Bar-Eli M, Sood AK
Source: Cancer Res, 2014 Mar 1;74(5), p. 1287-93.
EPub date: 2014 Feb 20.
Cross-talk between EphA2 and BRaf/CRaf Is a Key Determinant of Response to Dasatinib.
Authors: Huang J, Hu W, Bottsford-Miller J, Liu T, Han HD, Zand B, Pradeep S, Roh JW, Thanapprapasr D, Dalton HJ, Pecot CV, Rupaimoole R, Lu C, Fellman B, Urbauer D, Kang Y, Jennings NB, Huang L, Deavers MT, Broaddus R, Coleman RL, Sood AK
Source: Clin Cancer Res, 2014 Apr 1;20(7), p. 1846-55.
EPub date: 2014 Jan 31.
Platelet-derived growth factor receptor alpha (PDGFR?) targeting and relevant biomarkers in ovarian carcinoma.
Authors: Matsuo K, Nishimura M, Komurov K, Shahzad MM, Ali-Fehmi R, Roh JW, Lu C, Cody DD, Ram PT, Loizos N, Coleman RL, Sood AK
Source: Gynecol Oncol, 2014 Jan;132(1), p. 166-75.
EPub date: 2013 Oct 29.
Targeting SRC and tubulin in mucinous ovarian carcinoma.
Authors: Liu T, Hu W, Dalton HJ, Choi HJ, Huang J, Kang Y, Pradeep S, Miyake T, Song JH, Wen Y, Lu C, Pecot CV, Bottsford-Miller J, Zand B, Jennings NB, Ivan C, Gallick GE, Baggerly KA, Hangauer DG, Coleman RL, Frumovitz M, Sood AK
Source: Clin Cancer Res, 2013 Dec 1;19(23), p. 6532-43.
EPub date: 2013 Oct 7.
Predicting effects of kinase inhibitor in therapy for myeloid malignancies - the challenges in capturing disease heterogeneity.
Authors: Reikvam H, Nepstad I, Tamburini J
Source: Expert Opin Investig Drugs, 2013 Nov;22(11), p. 1365-70.
EPub date: 2013 Oct 7.
Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer.
Authors: Kang Y, Hu W, Ivan C, Dalton HJ, Miyake T, Pecot CV, Zand B, Liu T, Huang J, Jennings NB, Rupaimoole R, Taylor M, Pradeep S, Wu SY, Lu C, Wen Y, Huang J, Liu J, Sood AK
Source: J Natl Cancer Inst, 2013 Oct 2;105(19), p. 1485-95.
EPub date: 2013 Sep 23.
Impact of cardiovascular comorbidity on ovarian cancer mortality.
Authors: Shinn EH, Lenihan DJ, Urbauer DL, Basen-Engquist KM, Valentine A, Palmero L, Woods ML, Patel P, Nick AM, Shahzad MM, Stone RL, Golden A, Atkinson E, Lutgendorf SK, Sood AK
Source: Cancer Epidemiol Biomarkers Prev, 2013 Nov;22(11), p. 2102-9.
EPub date: 2013 Sep 17.
Tumour angiogenesis regulation by the miR-200 family.
Authors: Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, Bottsford-Miller J, Liu Y, Kim SB, Unruh A, Gonzalez-Villasana V, Huang L, Zand B, Moreno-Smith M, Mangala LS, Taylor M, Dalton HJ, Sehgal V, Wen Y, Kang Y, Baggerly KA, Lee JS, Ram PT, Ravoori MK, Kundra V, Zhang X, Ali-Fehmi R, Gonzalez-Angulo AM, Massion PP, Calin GA, Lopez-Berestein G, Zhang W, Sood AK
Source: Nat Commun, 2013;4, p. 2427.
Therapeutic synergy between microRNA and siRNA in ovarian cancer treatment.
Authors: Nishimura M, Jung EJ, Shah MY, Lu C, Spizzo R, Shimizu M, Han HD, Ivan C, Rossi S, Zhang X, Nicoloso MS, Wu SY, Almeida MI, Bottsford-Miller J, Pecot CV, Zand B, Matsuo K, Shahzad MM, Jennings NB, Rodriguez-Aguayo C, Lopez-Berestein G, Sood AK, Calin GA
Source: Cancer Discov, 2013 Nov;3(11), p. 1302-15.
EPub date: 2013 Sep 3.
Importance of adrenergic pathways in women's cancers.
Authors: Thaker PH, Sood AK, Ramondetta LM
Source: Cancer Biomark, 2013;13(3), p. 145-54.
Biologic effects of dopamine on tumor vasculature in ovarian carcinoma.
Authors: Moreno-Smith M, Lee SJ, Lu C, Nagaraja AS, He G, Rupaimoole R, Han HD, Jennings NB, Roh JW, Nishimura M, Kang Y, Allen JK, Armaiz GN, Matsuo K, Shahzad MM, Bottsford-Miller J, Langley RR, Cole SW, Lutgendorf SK, Siddik ZH, Sood AK
Source: Neoplasia, 2013 May;15(5), p. 502-10.
ATP11B mediates platinum resistance in ovarian cancer.
Authors: Moreno-Smith M, Halder JB, Meltzer PS, Gonda TA, Mangala LS, Rupaimoole R, Lu C, Nagaraja AS, Gharpure KM, Kang Y, Rodriguez-Aguayo C, Vivas-Mejia PE, Zand B, Schmandt R, Wang H, Langley RR, Jennings NB, Ivan C, Coffin JE, Armaiz GN, Bottsford-Miller J, Kim SB, Halleck MS, Hendrix MJ, Bornman W, Bar-Eli M, Lee JS, Siddik ZH, Lopez-Berestein G, Sood AK
Source: J Clin Invest, 2013 May 1;123(5), p. 2119-30.
EPub date: 2013 Apr 15.
Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer.
Authors: Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, Zhao Y, Reynolds S, Cheng H, Rupaimoole R, Cogdell D, Nykter M, Broaddus R, Rodriguez-Aguayo C, Lopez-Berestein G, Liu J, Shmulevich I, Sood AK, Chen K, Zhang W
Source: Cancer Cell, 2013 Feb 11;23(2), p. 186-99.
Latest research and treatment of advanced-stage epithelial ovarian cancer.
Authors: Coleman RL, Monk BJ, Sood AK, Herzog TJ
Source: Nat Rev Clin Oncol, 2013 Apr;10(4), p. 211-24.
EPub date: 2013 Feb 5.