Tumor natural killer cells

Follow-on studies are also recommended as needed. These include determination of potential test article effects on blood or tissue immunophenotypes (by flow cytometry or immunohistochemistry), natural killer cell, macrophage, or neutrophil function, host resistance to infection or tumors, and cell-mediated immunity. The important issue in all of these guidelines is this do not ignore signs of immunotoxicity, and assess these findings when observed. 

Takeda, K. et al., Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells, Nat. Med., 7, 94, 2001. 

Kalland, T., Forsberg, J.G. Natural killer cell activity and tumor susceptibility in female mice treated neonatally with diethylstilbestrol, Cancer Res. 51, 134, 1981. 

See D, Mason S, Roshan R. (2002) Increased tumor necrosis factor TNF-a and natural killer cell (NK) function using an integrative approach in late stage cancers. Immunol Invest 31 137-153. 

Bacillus Calmette-Guerin (BCG) is a viable attenuated strain of Mycobacterium bovis. Nonviable strains of the bacterium also have been shown to augment the immune response. The smallest active compound derived from BCG thus far has been identified as muramyl dipeptide. The T cell is a principal target for BCG. It also appears to stimulate natural killer cells, which in turn can kill malignant cells. It has been suggested that BCG cross-reacts immunologically with tumor cell antigens. 

The effect of echinacea on the immune system is controversial. In vivo human studies using commercially marketed formulations of E purpurea have shown increased phagocytosis, total circulating white blood cells, monocytes, neutrophils, and natural killer cells but not immunostimulation. In vitro, Epurpurea juice increased production of interleukins-1, -6, and -10, and tumor necrosis factor- by human macrophages. Enhanced natural killer cell activity and antibody-dependent cellular toxicity was also observed with E purpurea extract in cell lines from both healthy and immunocompromised patients. Studies using the isolated purified polysaccharides from Epurpurea have also shown cytokine activation. Polysaccharides by themselves, however, are unlikely to accurately reproduce the activity of the entire extract. 

Hoskin DW, Mader JS, Furlong SJ, Conrad DM, Blay J (2008) Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (review). Int J Oncol 32(3) 527-535... 

Marcus et al. reported that anti GM1 ganglioside antibody can be used as a T cell marker (11, 12, 13). In collaboration with Tada s group of the University of Tokyo we very recently found that antibody to asialoganglio-side GM1 specifically labels mouse natural killer cells and that the antibody selectively kills the cells in the presence of complement (14). Natural killer cells are known by their specific ability to attack tumor cells. We also have evidence that certain gangliosides are capable of eliciting autoimmune diseases experimentally which we called the ganglioside syndrome (JJ5). For example, some brain gangliosides produce autoimmune lesions in peripheral nerve in susceptible rabbits. This may correspond to the human... 

Melder, R.J., Koenig, G.C., Witwer, B.P., Safabakhsh, N., Munn, L.L. and Jain, R.K. (1996) During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Nat. Med., 2, 992-997. 

Recent studies further suggest that LF may have a role in the development and progression of tumors (Tsuda et al., 2002). Orally administered bovine LF has been found to inhibit the development of tumors in the colon, oesophagus and lung carcinogenesis in a rat or mouse model, but the mode of action remains to be resolved (Sekine et al., 1997 Ushida et al., 1999 Kuhara et al., 2000). The anti-tumor activity may be mediated by the enhanced cytokine production or the activating effect on natural killer cells and be independent of the iron-saturation level. 

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