T U M O R I M M U N O L O G Y P R O G R A M • Currently studying the expression of IL-12 receptor in the T cells from tumor bearers, in order to determine if the decreased levels of IFN-gamma observed in T cells from tumor bearers might also be explained in part because of a low level of expression of this receptor, in addition to low levels of IL-12. IL-12 is known to stimulate the production of interferongamma (IFN-γ) in naïve T cells. VLADIMIR VINCEK, M.D., PH.D. Associate Professor of Pathology DESCRIPTION OF RESEARCH Progress in the understanding of molecular events involved in the development and progression of human disease is revolutionizing the way diseases are diagnosed and treated. Physicians and scientists now are harnessing the power of molecular techniques to diagnose and prognosticate pathologic disorders. Furthermore, it is now possible to direct therapeutic agents to specific products expressed by diseased cells without affecting normal tissues. On the other hand, while standard histopathologic methods maintain tissue architecture for morphologic assessment, they do not preserve macromolecules. The extraction of nucleic acids from formaldehyde-fixed, paraffinembedded tissue, the most widely available material for clinical studies, is a notoriously unreliable and irreproducible process. Therefore, macromolecules usually are extracted from fresh or snapfrozen tissue specimens. Fresh or frozen tissue specimens, however, have limited value for the assessment of histomorphology and cannot be utilized for long-term retrospective studies. Similarly, currently available tissue preservatives that protect nucleic acids cause considerable damage to the cell and tissue architecture and render them unsuitable for histomorphologic evaluation. Current studies in this laboratory show that it is feasible to simultaneously protect histomorphology and the integrity of macromolecules in fixed and processed tissue. The UMFIX reagent, developed in collaboration with other members of the Department of Pathology, seems to provide enormous advantage over the conventional fixation methods in allowing diagnosis, prognostication, and identification of treatment targets in patient samples. SELECTED PUBLICATIONS 2002 Malek, TR, Yu, A, Vincek, V, Scibelli, P, and Kong, L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17:167-78, 2002. Morales, A, Essenfeld, H, Dubane, C, Vincek, V, and Nadji, M. Continuous-specimen flow, highthroughput, 1-hour tissue processing. Archives of Pathology & Laboratory Medicine 126:584-90, 2002. 2003 Vincek, V, Knowles, J, and Nassiri, M. p63 mRNA expression in normal human tissue. Anticancer Research 23:3945-48, 2003. Jacob, SE, Nassiri, M, Kerdel, FA, and Vincek, V. Rapid measurement of multiple cytokines in psoriasis patients and correlation with disease severity. Mediators of Inflammation 12:309-13, 2003. Adkins, B, Bu, Y, Vincek, V, and Guevara, P. The primary responses of murine neonatal lymph node CD4 + cells are Th2-skewed and are sufficient for the development of Th2-biased memory. Clinical & Developmental Immunology 10:43- 51, 2003. Vincek, V, Nassiri, M, Nadji, M, and Morales, AR. A novel tissue preservative that protects macromolecules (DNA, RNA, protein) and histomorphology in clinical samples. Laboratory Investigation 83:1-9, 2003. UM/<strong>Sylvester</strong> <strong>Comprehensive</strong> <strong>Cancer</strong> <strong>Center</strong> Scientific Report <strong>2004</strong> 127
T U M O R I M M U N O L O G Y P R O G R A M Jacob, SE, Berman, B, Nassiri, M, and Vincek, V. Topical application of imiquimod 5% cream to keloids alters expression genes associated with apoptosis. The British Journal of Dermatology 149:1-4, 2003. HIGHLIGHTS/DISCOVERIES • Applied for a patent for an alcohol-based UMfix preservative that preserves histomorphology and macromolecules; the patent currently is pending. 128 UM/<strong>Sylvester</strong> <strong>Comprehensive</strong> <strong>Cancer</strong> <strong>Center</strong> Scientific Report <strong>2004</strong>