Serum factor, cytotoxic

There is a long-standing hypothesis that the microvasculature plays a pathological role in forms of chronic inflammatory polyarthritis, particularly RA (Rothschild and Masi, 1982). One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. Blake et al. (1985) have su ested that the vascular abnormalities associated with RA may be linked to oxidized lipoproteins because they are cytotoxic to endothelial cells. 

Sinkovics JG, Cabiness JR, Shullenberger CC. Disappearance after chemotherapy of blocking serum factors as measured in vitro with lymphocytes cytotoxic to tumor cells. Cancer. 1972 30 1428-37. 

Sethi, K. K., and Brandis, H., 1972, In vitro cytotoxicity of normal serum factor(s) on neuraminidase-treated Ehrlich ascites cells, Z. Immun. Forsch. 143 426. 

Methotrexate is administered by the intravenous, intrathecal, or oral route. Up to 90% of an oral dose is excreted in the urine within 12 hours. The drug is not subject to metabolism, and serum levels are therefore proportionate to dose as long as renal function and hydration status are adequate. Dosages and toxic effects are listed in Table 55-3. The effects of methotrexate can be reversed by administration of leucovorin (citrovorum factor). Leucovorin rescue has been used with accidental overdose or experimentally along with high-dose methotrexate therapy in a protocol intended to rescue normal cells while still leaving the tumor cells subject to its cytotoxic action. 

Serum contains complement which may interfere in virus or cytotoxicity assays. This can be inactivated by heating the serum to 56°C for 30 min but this may also destroy some growth factors. 

Inflammatory mediators in biological fluids (e.g., BAL fluid and serum) can be measured with either bioassays or ELISA. A cytotoxicity bioassay using L929 cells has been used to measure TNF-a in biological fluids collected from rabbits (22). While the availability of rabbit specific reagents can be a limiting factor in the measurement of inflammatory mediators, rabbit specific immunoassays have been described for the chemokines IL-8, GRO, and MCP-1 (23-26). 

Constitutive activation of the PI3-K - Akt/PKB survival signaling pathway is a likely mechanism by which many cancers become refractory to cytotoxic therapy. In LNCaP prostate cancer cells, the PTEN is inactivated, leading to constitutive activation of Akt/PKB and resistance to apoptosis. However, apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment with PI3-K inhibitors. Surprisingly, androgen, epidermal growth factor, or serum can protect these cells from apoptosis, even in the presence of PI3-K inhibitors and without activation of Akt/PKB, indicating the activity of a novel, Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level prior to caspase 3 activation and release of cytochrome c from mitochondria (Carson et al., 1999)... 

Apart from the presence of proteins, several other factors can influence NM behavior in culture media, including the salt composition, the pH, or the buffer capacity. Using gold nanoparticles (AuNP) of three sizes Maiorano et al. [24] demonstrated that the nanoparticle-protein interactions are differendy mediated when AuNP are suspended in two common cell culture media (DMEM and RPMI) supplemented with fetal bovine serum. An increased protein coating and different size distribution were observed in AuNP suspended in DMEM in comparison to RPMI. Most impor-tantiy, differences were also found in the biological responses of two cell lines (HeLa and U937), as the intracellular internalization and cytotoxicity were higher in cells exposed to AuNP in RPMI, where the protein corona was less abundant. 

The compounds tested showed mitogenic effects,i.e. they stimulated lymphocyte proliferation. Astonishingly, a DIVEMA-DNP conjugate did not induce the production of DNP-specific antibodies. Our results suggest that this is due to the formation of DNP-specific active suppressor cells. Using serum free culture media, we could show for the first time that DIVEMA and derivatives stimulate macrophages to release cytotoxic factors into the supernatant. However, no significant release of lytic enzymes was detected. 

ZZ) this may be due to the fact that these authors used serum-containing culture media. Our results demonstrate that even chemically modified DIVEMA causes - at least in vitro - the same biological effect (release of cytotoxic factors) as DIVEMA itself. This aspect is especially important if one uses DIVEMA as a carrier polymer for antitumour agents hoping to retain immune stimulating properties. 

W3. Waage, A., Espevik, T., and Lamvik, J. Detection of tumor necrosis factor-like cytotoxicity in serum from patients with septicaemia but not from untreated cancer patients. Scand. J. Immunol. 24, 739-743 (1986). 

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