Tumor mediated lysis

Gruber, M Schodin, B A., Wilson, E. R., and Kranz, D. M. (1994) Efficient tumor cell lysis mediated by a bispecific single-chain antibody expressed in Escherichia colt J Immunol. 152, 5368—5374. 

Role of NKG2D in tumor cell lysis mediated by human NK cells Cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin. Eur. J. Immunol. 31(4), 1076-1086. 

An important immune function to evaluate in the context of immuno-deficiency, and one that represents a form of nonspecific immunity/host resistance, is the function of natural killer (NK) cells. NK cells are lymphocytes distinct from either B-cells or T-cells, which contribute to immunocompetence by mediating major histocompatibility complex-independent cytotoxicity (Lotzova 1993). For the purposes of these studies, a combined measurement of both basal and augmented NK cell function was used. In this assay, murine splenoc5des were exposed for 24 hours to various concentrations of drugs in the presence or absence of an optimum concentration of recombinant IL-2 (Thomas et al. 1993). The cells were then washed and cocultured for 4 hours with radiolabeled YAC-1 tumor cells (a murine NK-sensitive cell line). Tumor cell lysis was quantitated as described above for the CTL procedure. 

El Ayachi N. Begin M. Mercier D, Ells G, OthD. 8usceptibility of RDM4 lymphoma cells to LAK-mediated lysis is decreased in tumor bearers fed fish oil high fat regimen. Cancer Lett 1990 49 217-224. 

Jenski LJ, Sturdevant LK, Ehringer WD, Stillwell W. Omega-3 fatty acid modification of membrane structure and function 1. Dietary manipulation of tumor cell susceptibility to cell and complement-mediated lysis. Nutr Cancer 1993 19 135-146. 

Tumor cell killing by granulocytes was most potently triggered by FcaRI-directed bispecific constructs [92]. Recent studies indicate that simultaneous engagement of FcaRI and FcyRI results in enhanced PMN-mediated tumor cell lysis [114], suggesting that new Ab cocktails, e.g. combinations of IgG and IgA Abs, may improve the efficacy of current clinical protocols. 

Gruber M, Schodin BA, Wilson ER, Kranz DM. Efficient tumor cell lysis mediated... 

The antibody-dependent lysis of tumor cells by PMNs exhibited some of the characteristics of damage mediated by products of the burst in the presence of tumor cells there was increased consumption of O2, increased formation of O and activation of the hexose monosphosphate shunt However, although a reduction in the concentration of O2 in the medium inhibited lysis neither catalase nor superoxide dismutase inhibited. The lack of effect on these enzymes was attributed to their inability to interpose themselves between the plasma membranes of the PMN and its target. Similar conclusions were reached by Clark, and Klebanoff whose data incriminated the products of the burst by the reduced killing of tumor cells by PMNs from patients with chronic granulomatous disease. Myeloperoxidase, however, appeared not to he required since neither azide or cyanide inhibited and killing by PMNs from patients with inherited deficiency of myeloperoxidase was normal. 

For complement-dependent cytotoxicity, a complex cascade of protein binding and cleavage occurs that culminates in final complement mediated effector functions of phagocytosis, recruitment and activation of leukocytes, and osmotic lysis. It has been reported that Rituximab (anti-CD20) utilizes a complement-dependent mechanism for tumor cell destruction [14], If the desired effect of a therapeutic antibody is complement-dependent activity, the isotype subgroup chosen should be one that binds to complement proteins (IgGl or IgG3). 

Monoclonal antibodies may be used as passive immunotherapy to treat malignancies. They react with specific antigens present on the surface of tumor cells and result in cell destruction. Rituximab was the first MoAb approved in the United States for the treatment of cancer. It is a chimeric MoAb directed against cluster differentiation 20 (CD20) markers, which are expressed on over 90% of B-cell NHL tumors. Rituximab is thought to result in B-cell depletion by a number of mechanisms, including complement-mediated and antibody-dependent cell lysis and induction of apoptosis. 

The modulation of the immune response is highly relevant in tumor cell destruction. The research of Guruvayoorappan and Kuttan[64] focused on the effect of amentoflavone (1) on cell-mediated immune responses in normal and tumor-bearing control animals. The treatment with amentoflavone (1) significantly enhanced the activity of natural killer cells in normal (42.8% cell lysis) and tumor-bearing animals (48.2% cell lysis) on the fifth day, which was... 

Morimoto, H. and Bonavida, B. (1992) Diphtheria toxin- and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha. J Immunol, 149, 2089-2094. 

Indications for renal replacement therapy in the acute setting and for other disease processes are different from those for ESRD. A common mode of ESRD therapy in the outpatient setting is intermittent hemodialysis (IHD) where a patient receives intense treatment over the course of a few hours several times a week. Acute renal failure in the inpatient setting is often treated with continuous renal replacement therapy (CRRT), which is applied for the entire duration of the patient s clinical need and relies upon hemofiltration to a higher degree than IHD (Meyer, 2000). Other nonrenal indications for CRRT are based on the theoretical removal of inflammatory mediators or toxins and elimination of excess fluid (Schetz, 1999). These illnesses include sepsis and systemic inflammatory response syndrome, acute respiratory distress syndrome, congestive heart failure with volume overload, tumor lysis syndrome, crush injury, and genetic metabolic disturbances (Schetz, 1999). 

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