Tumor, CEUS

T-Lymphocytes (4,5) and other cellular components of the immune system also have equally wide implications in regulation of the normal immune system. The T-lymphocytes play a central role in the body s response to harmful antigens and tumor—host interaction (4). Responses involve antigens derived from vimses, bacteria, parasites, and tumors. T-ceUs also participate in the immune surveillance response, where self-antigens are recognized, but usually sequestered within the cell and, when exposed, become markers of cellular damage. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Direct. Some radionucHdes are packaged in solution for direct sampling (qv) via a septum and injection into the patient. GalHum-67 is a marker of inflammation, infection, and various tumor types. Its half-life is 78.3 h and it is suppHed as the gallium citrate salt. Indium-111 chloride is suppHed for the labeling of white blood ceUs. The In chloride is mixed with oxine (9-hydroxyquinoline) to form a lipophilic, cationic In oxine complex, which enters the white blood ceU. The complex dissociates within the ceU, and the cationic In " ion is trapped within the ceU, owing to its charge. 

Skladanowski, A., and Konopa, J., 1993, Adriamycin and daunomycin induce programmed ceU death (apoptosis) in tumor ceUs. Biochem. Pharmacol. 46 375-382 Slater, A.F.G., Nobel, C.S.L, Maelaro, E., Bustamante, J., Kimland, M., and Orrenius, S., 1995, Nitrone spin traps and a nitroxide antioxidant inhibit a common pathway in thymocyte apoptosis. Biochem. J. 306 771-778 Snyder, R., Jowa, L., Witz, G., Kalf, G., and Rushmore, T., 1987, Formation ofreactive metabolites from benzene. Arch. Toxicol. 60 61-64. 

Stoka, V., Turk, B., Schendd, S.L., Kim, T.-H., Cirman, T, Srripas, SJ., EUerby, L.M., Bredesen, L., Freeze, H, Abrahamson, M., Bromme, D., Krajewski, S., Reed, J.C., Yin, X.-M., Turk, V., and Salvesen G.S., 2001, Lysosomal Protease Pathways to Apoptosis. Cleavage of Bid, not pro-caspases, is the most likely route. J. Biol. Chem. 276 3149-3157 Srm, X. and Ross, D., 1996, Quinone-induced apoptosis in human colon adenocarcinoma ceUs via DT-diaphorase mediated bioactivation. Chem. Biol. Interact. 100 267-76 Taatjes, D.J. and Koch, T.H., 2001, Nuclear targeting and retention of anthracycUne antitumor dmgs in sensitive and resistant tumor ceUs. Curr. Med Chem. 8 15-29 Tarr, M. and van Helden, PT)., 1990, Inhibition of transcription by adriamycin is a... 

Xia, P., Wang, L, Gamble, J.R. and Vadas, M.A., 1999, Activation of sphingosine kinase by tumor necrosis factor-a inhibits apoptosis in human endothelial ceUs, J. Biol. Chem. 274 34499-34505. 

Silva et al., 1996). Furthermore, Leflimomide blocks tumor necrosis factor (TNF)-a-mediated cellular responses in T-ceUs by inhibiting nuclear factor kB, a mechanism that also depends on pyrimidine biosynthesis (Manna and Aggarwal,... 

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