SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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C L I N I C A L O N C O L O G Y R E S E A R C H P R O G R A M currently are looking at novel agents against multiple myeloma (MM). The NCI-sponsored phase I/II clinical trial is examining arsenic trioxide + ascorbic acid in the treatment of refractory/ relapsed MM. Initial results demonstrate that this combination is effective against myeloma that is resistant to standard chemotherapy (including thalidomide) with acceptable toxicity. The laboratory component of these studies seeks to understand how arsenic kills myeloma, how ascorbic acid potentiates that killing, how myeloma cells become resistant to arsenic, and which host (i.e., patient) factors may help the myeloma survive in the bone marrow. SELECTED PUBLICATIONS 2002 Gray Parkin, K, Stephan, RP, Apilado, RG, Lill- Elghanian, DA, Lee, KP, Saha, B, and Witte, PL. Expression of CD28 by bone marrow stromal cells and its involvement in B lymphopoiesis. Journal of Immunology 169:2292-302, 2002. Baumgartner, R, Durant, P, van Gessel, Y, Chattopadhyay, S, Beswick, RL, Tadaki, DK, Lasbury, M, Lee, CH, Perrin, P, and Lee, KP. Evidence for the requirement of T cell costimulation in the pathogenesis of natural Pneumocystis carinii pulmonary infection. Microbial Pathogenesis 33:193-201, 2002. Strbo, N, Yamazaki, K, Lee, KP, Rujkavina, D and Podack, ER. Heat shock fusion protein gp96-Ig mediates strong CD8 CTL expansion in vivo. American Journal of Reproductive Immunology 48:220-25, 2002. 2003 Tadaki, DK, Williams, A, Lee, KP, Kirk, AD, and Harlan, DM. Porcine CD80: cloning, characterization, and evidence for its role in direct human T-cell activation. Xenotransplantation 10: 252- 58, 2003. Lindner. I, Kharfan-Dabaja, M, Ayala. E, Kolonias, D, Cejas, P, and Lee, KP. Induced differentiation of chronic myelogenous leukemia to dendritic cells down-regulates BCR-ABL gene expression. Journal of Immunology 171:1780-91, 2003. McCafferty-Grad, J, Bahlis, NJ, Krett, N, Reis, I, Lee, KP, and Boise, LH. Arsenic trioxide utilizes caspase dependent and caspase independent death pathways in myeloma cells. Molecular Cancer Therapeutics 2:1155-64, 2003. HIGHLIGHTS/DISCOVERIES • Direct activation of PKC causes normal human hematopoietic CD34 + stem cells to differentiate into DC. • PKC activation causes many myeloid leukemias to differentiate into immunologically functional “leukemic” DC. These cells have potential utility as “cellular” anti-leukemia vaccines. • Specific intracellular signaling pathways downstream of PKC activation control specific aspects of DC differentiation. • Arsenic trioxide + ascorbic acid is an effective combination in the treatment of refractory/relapsed myeloma. Bahlis, NJ, McCafferty-Grad, J, Jordan- McMurry, I, Neil, J, Reis, I, Kharfan-Dabaja, M, Eckman, J, Goodman, M, Fernandez, HF, Boise, LH, and Lee, KP. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clinical Cancer Research 8:3658-68, 2002. UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 43
C L I N I C A L O N C O L O G Y R E S E A R C H P R O G R A M STEVEN E. LIPSHULTZ, M.D. Professor and Chairman of Pediatrics DESCRIPTION OF RESEARCH Dr. Lipshultz’s research focuses on the prevention of cardiomyopathy and heart failure in children and young adults. He developed the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Pediatric Cardiomyopathy Registry (PCMR) to better understand genetic and metabolic cardiomyopathies; the NHLBI P2C2 HIV study to better understand infectious and inflammatory cardiomyopathies; and the NCI Dana-Farber Cancer Institute childhood leukemia and NCI Children’s Oncology Group childhood cancer survivor cohorts to better understand toxic cardiomyopathies from anthracycline chemotherapy and mediastinal irradiation. Further understanding of clinical phenotypes, human syndrome delineation, epidemiology, and the natural history of these pediatric diseases has resulted from these cohorts. SELECTED PUBLICATIONS 2002 Lipshultz, SE, Lipsitz, SR, Sallan, SE, Simbre, VC 2nd, Shaikh, SL, Mone, SM, Gelber, RD, and Colan, SD. Long-term enalapril therapy for left ventricular dysfunction in doxorubicintreated survivors of childhood cancer. Journal of Clinical Oncology 20:4517-22, 2002. Harmon, WG, Dadlani, GH, Fisher, SD, and Lipshultz, SE. Myocardial and pericardial disease in HIV. Current Treatment Options in Cardiovascular Medicine 4:497-509, 2002. Lipshultz, SE, Giantris, AL, Lipsitz, SR, Kimball, Dalton V, Asselin, BL, Barr, RD, Clavell, LA, Hurwitz, CA, Moghrabi, A, Samson, Y, Schorin, MA, Gelber, RD, Sallan, SE, and Colan, SD. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91- 01 Acute Lymphoblastic Leukemia protocol. Journal of Clinical Oncology 20:1677-82, 2002. 2003 Zareba, KM and Lipshultz, SE . Cardiovascular complications in patients with HIV infection. Current Infectious Disease Reports 5:513-20, 2003. Constine, LS, Hinkle, AS, French, CA, Kozlowski, AM, Proukou, C, Lipsitz, SR, Miller, TL, Vermilion, RP, Rifai, N, and Lipshultz, SE. Radiation-associated risk factors for premature cardiovascular disease in childhood cancer survivors include accelerated atherosclerosis. International Journal of Radiation Oncology Biology Physics 57(2 Supplement):S199-200, 2003. Adams, MJ, Lipshultz, SE, Schwartz, C, Fajardo, LF, Coen, V, and Constine, LS. Radiation-associated cardiovascular disease: manifestations and management. Seminars in Radiation Oncology 13:346-56, 2003. Lipshultz, SE, Fisher, SD, Lai, WW, and Miller, TL. Cardiovascular risk factors, monitoring, and therapy for HIV-infected patients. AIDS 17 Supplement 1:S96-122, 2003. Fisher, SD, Bowles, NE, Towbin, JA, and Lipshultz, SE. Mediators in HIV-associated cardiovascular disease: a focus on cytokines and genes. AIDS 17 Supplement 1:S29-35, 2003. Lipshultz, SE, Somers, MJ, Lipsitz, SR, Colan, SD, Jabs, K, and Rifai, N. Serum cardiac troponin and subclinical cardiac status in pediatric chronic renal failure. Pediatrics 112:79-86, 2003. Al-Attar, I, Orav, EJ, Exil, V, Vlach, SA, and Lipshultz, SE. Predictors of cardiac morbidity and related mortality in children with acquired immunodeficiency syndrome. Journal of the American College of Cardiology 41(9):1598-605, 2003. Benun, J, Fisher, SD, Orav, EJ, Schwartz, ML, Exil, V, Messere, C, and Lipshultz, SE . Cardiac management by pediatricians versus pediatric cardiologists in an inpatient academic center. American Heart Journal 145:424-9, 2003. 44 UM/Sylvester Comprehensive Cancer Center Scientific Report 2004
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