Tumor cytotoxicity

Recently, considerable evidence has emerged that implicates the macrophage as a major effector of tumor cytotoxicity and/or cytostasis. Both synthetic... 

Catectin promotes tumor cytotoxicity activates macrophages and neutrophils enhances IL-2 receptor expression on T cells inhibits antibody secretion... 

Drugs used in cancer chemotherapy are cytotoxic drugs, hormones, plant derivatives, radioactive isotopes, and miscellaneous agents (e.g., procarbazine, hydroxyurea, mitotane). The plant-based drugs vincristine, vinblastine, vinorel-bine, etoposide, and campothecins. Radioactive isotopes, such as 131 iodine (131 I), are used in the treatment of thyroid tumors. Cytotoxic drugs (e.g., cis-platin, cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, and methotrexate are used for the treatment of cancer. 

The in vivo metabolism of capecitabine (1) to the active tumor cytotoxic substance 5-fluorouracil (5) is now fairly well understood. When capecitabine is administered orally it is delivered to the small intestine, where it is not a substrate for thymidine phosphorylase in intestinal tissue, and so passes through the intestinal mucosa as an intact molecule and into the bloodstream. When 1 reaches the liver, the carbamate moiety is hydrolyzed through the action of carboxylesterase enzymes, liberating 5 -deoxy-5-fluorocytidine (5 -DFCR, 10). DFUR is partially stable in systemic circulation, but eventually diffuses into tumor cell tissue where it is transformed into 5 -deoxy-5-fluorouridine (5 -DFUR, 9) by cytidine deaminase, an enzyme present in high concentrations in various types of human cancers compared to adjacent healthy cells (although it is present in significantly lower levels in the liver). Within the tumor, 5-... 

Therefore, we compared the tumor cytotoxicity between EPA ethylester and the accelerated test-formed by-products in in vitro models. The inhibitory effects of E-1 (EPA ethylester dimer) and E-2 (EPA hydroxyethylester) isolated from EPAD on DNA synthesis in LLC cells were stronger than those of EPA ethylester Fig. (9) . Furthermore, it was found that the effects of E-1 (EPA ethylester... 

Frei, K., Siepl, C., Groscurth, P, Bodmer, S., Schwerdel, C., and Fontana, A., Antigen presentation and tumor cytotoxicity by interferon-y-treated microglial cells, Eur. J. Immunol., 17, 1271, 1987. 

Chaplin, D. J. and Acker, B. (1987) The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069. Evidence for therapeutic gain. Int. J. Radiat. Oncol. Biol. Phys. 13, 579-585. 

Arakaki, N. et al., Involvement of oxidative stress in tumor cytotoxic activity of hepatocyte growth factor/scatter factor, J. 5io/. Chem., 274,13541,1999. 

TNFa Macrophage, B and Catectin promotes tumor cytotoxicity ... 

Lu GY, Huang SM, Liu ST, Liu PY, Chou WY, Lin WS. Caffeine induces tumor cytotoxicity via the regulation of alternative splicing in subsets of cancer-associated genes. Int J Biochem Cell Biol 2014 47 83-92. 

Figure 2. "Stimulated and "Activated" macrophage to non-cytotoxic and tumor-cytotoxic states.

Dominguez-Perles, R., Moreno, D.A., and Garcia-Viguera, C. 2012. Analysis ofthe tumoral cytotoxicity of green tea-infusions enriched with broccoli. Food Chemistry, 132(3), 1197-1206. doi 10.1016/j.foodchem.2011.11.076. 

Zhang HG, Kim H, Liu C, Yu S, Wang J, Grizzle WE, Kimberly RP, Barnes S. Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. Biochim Biophys Acta. 2007 1773 1116-23. 

NO donors have the potential to be tumor cytotoxic agents. Thus, nitric oxide donors have the dual functions of both sensitizing tumor cells to chemotherapy and immunotherapy and are also involved in the regulation and inhibition of metastasis. NO donors constitute a promising new class of mmor cytotoxic agents. In this section, we introduce some examples of the cytotoxic characteristic that have been reported. 

Anasagasti, M.J., Alvarez, A., Martin, J.J., Mendoza, L., and Vidal-Vanaclocha, F. (1997a). Sinusoidal endothelium release of hydrogen peroxide enhances very late antigen-4-mediated melanoma cell adherence and tumor cytotoxicity during interleukin-1 promotion of hepatic melanoma metastasis in mice. Hepatology 25(4), 840-846. 

Carretero, J., Obrador, E., Esteve, J.M., Ortega, A., Pellicer, J.A., Sempere, F.V., and Estrela, J.M. (2001). Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. J. Biol. Chem. 276(28), 25775-25782. 

Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic. Biol. Med. 31(5), 642-650. 

Carney, J.R. and Scheuer, P.J. (1993) Popolohuanone E, a topoisomerase-II inhibitor with selective lung tumor cytotoxicity from the Pohnpei sponge Dysidea sp. Tetrahedron Lett., 34, 3727—3730. 

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