Biochemistry and Molecular Biology, Pathology
Bressler Research Building,
My area of clinical interest is in genito-urinary malignancies, including developing multi-modal therapies in patients with high risk prostate cancer and recurrent prostate cancer. In addition, our aim is to help identify and develop active treatment regimens for advanced, hormone resistant prostate cancer and advanced bladder cancer. Another area of active ongoing work is related to the problem of bone metastasis, which is a particularly relevant issue in advanced prostate cancer. We are developing and testing several novel treatment combinations for all the above disease states of prostate cancer. Currently I am the Principal Investigator of ten active clinical trials in prostate cancer and bladder cancer.
My laboratory research is directed in two areas:
- We are using two pre-clinical mouse models of prostate cancer, including a xenograft model and a transgenic model (TRAMP) to study the antitumor effects of chemotherapy and hormone ablation, with the aim to determine optimal integration of these treatment modalities for therapeutic effect. These studies are being complimented with immunohistochemical analysis of various markers of apoptosis, angiogenesis and cell proliferation.
- The second area of research is to study mechanisms of drug resistance and cell signaling in human prostate cancer cells that have been selected for resistance to agents that disrupt cellular calcium homeostasis and microtubular stability.
Our research program has been supported by clinical grants, the National Institutes of Health and the Department of Veterans Affairs.
Medical Genito-Urinary Oncology
Selected Recent Publications
Tang, Y, Khan, MA, Goloubeva, O, Lee, DI, Jelovac, D, Brodie, AM, and Hussain, A. Docetaxel followed by castration improves outcomes in LNCaP prostate cancer-bearing SCID mice. Clin. Cancer Res, 12(1): 169-174, 2006.
O'Neill, J, Velalar, CN, Lee, DI, Zhang, B, Nakanishi, T, Tang, Y, Selary, F, Ross, D, Meltzer, SJ, and Hussain, A. Thapsigargin resistance in human prostate cancer cells. Cancer, 107(3): 649-659, 2006.
Lee, DI, Sumbilla, C, Lee, M, Velalar, CN, Klein, MG, Ross, DD, Inesi, G, and Hussain, A. Mechanisms of resistance and adaptation to thapsigargin in PC3 and DU145 prostate cancer cells. Arch. Biochem. Biophys., 464: 19-27, 2007.
Tang, Y, Wang, L, Goloubeva, O, Khan, MA, Zhang, B, and Hussain, A. Divergent effects of castration on prostate tumors in transgenic adenocarcinoma of mouse prostate mice: possible implications for therapy. Clin Cancer Res, 14:2936-2943, 2008.
Zafar, S, Hussain, A, Liu, D, and Inesi, G. Specificity of ligand binding to transport sites: Ca2+ binding to the Ca2+ transport ATPase and its dependence on H+ and Mg2+. Arch. Biochem. Biophy, 476(1): 87-94, 2008.
Hussain, A, DiPaola, R, Baron, A, Higano, C, Tchekmedyian, N, and Johri, A. Phase II trial of patupilone in castration resistant prostate cancer. Annals Oncol, 20(3):492-497, 2009.
Kouiavskaia, DV, Berard, CA, Datena, E, Hussain, A, Dawson, N, Klyushnenkova, EN, and Alexander, RB. Vaccination with agonist peptide PSA: 154-163(155L) derived from prostate specific antigen induced CD8 T-cell response to the native peptide PSA: 154-163 but failed to induce reactivity against tumor targets expressing PSA. A phase 2 study in patients with recurrent prostate cancer. J. Immunotherapy,32(6):655-66, 2009.
Smith, V, Dai, F, Spitz, M. Peters, G, Fiebey, H-H, Hussain, A, and Burger, A. Telomerase activity and telomere length in human tumor cells with acquired resistance to anticancer agents. J. Chemotherapy, 21: 542-549, 2009.
Tang, Y, Wang, L, Goloubeva, O, Khan, MA, Lee, DI, and Hussain, A. The relationship of neuroendocrine carcinomas to anti-tumor therapies in TRAMP mice. Prostate, 69: 1763-1773, 2009.
Tang Y, Hamburger A, Wang L, Khan MA, Hussain A. Androgen deprivation and stem cell markers in prostate cancer. Intl. J. Clin Exp Path, 3(2): 128-138, 2010.
Mullins, CD, Onukwugha, E, Seal, B, and Hussain, A. Trends in health disparities in staging of prostate cancer patients in the United States. Urology, 76(3): 566-572, 2010.
DiBiase, S, Hussain, A, Kataria, R, Amin, P, Dawson, N, Kwok, Y. Long term results of a prospective phase II study of long term androgen ablation, pelvic radiotherapy, brachytherapy boost and adjuvant docetaxel in patients with high risk prostate cancer. Intl. J. Rad. Oncol. Biol. Phys. (in press)
Hussain A, Wu Y, Mirmiran A, DiBiase S, Goloubeva O, Bridges B, Mannuel H, Engstrom E, Dawson N, Amin P, Kwok Y. Long term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation and androgen deprivation in high risk prostate cancer with or without prior prostatectomy. Intl. J. Rad. Oncol. Biol. Phys. (in press)
Onukwugha E, Mullins CD, Hsu VD, Seal B, Hussain A. Impact of urologists and medical oncologists on treatment in elderly men with stage IV prostate cancer. Urology (in press)
Mullins CD, Montgomery R, Abernethy AP, Hussain A, Pearson D, Tunis S. Recommendations for clinical trials of off-label drugs used to treat advanced stage cancer. J. Clin. Oncol. (in press)
Picus J, Halabi S, Monk J, Hussain A, Philips G, Kaplan E, Ahles T, Gu L, Vogelzang N, Kelly W, Small E. Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B 9782. Cancer (in press)