Anti-cancer drugs
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Cytotoxic as well as immunomodulatory effects of mistletoe extracts and their components have been described and seem to depend upon the host tree, the manufacturing process and the composition of the different components present in the extracts. In vitro studies showed that a fermented mistletoe extract derived from Viscum album L. grown on pine trees was less cytotoxic to peripheral blood mononuclear cells (PBMC) than other preparations. This finding could be related to its very low content of mistletoe lectins. ⋯ In the supernatants of stimulated PBMC from healthy individuals, type-1 (interferon-gamma and interleukin-2) and type-2 (interleukin-4 and interleukin-5) associated cytokines were detected in about 20%. In patients with colorectal tumours, however, reduced frequency, suggesting a functional impairment of certain immunocompetent cells in these patients. These studies may help to evaluate properties of the natural and the specific immune system.
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Extracts produced from Viscum album L. (mistletoe) as well as certain isolated components are able to stimulate different functions of the immune system. The natural killer cells have been suggested as one of the candidates for direct tumour cell destruction. These cells are defined by their ability to mediate non-major histocompatibility complex (MHC) restricted cytotoxicity without prior sensitization against a specific antigen. ⋯ In this regard it is interesting that mistletoe extracts are able to stimulate natural killer cell-mediated cytotoxicity in vitro directly as well as indirectly in a cytokine-like manner, with the active components being carbohydrates rather than lectins. Clinical application of mistletoe extracts or isolated lectins is reported to induce augmentation of both number and activity of natural killer cells in peripheral blood in a dose-dependent manner; however, non-responders also have been described. In future work it has to be clarified whether a mistletoe-derived modulation of the natural killer system is of benefit in the tumour defence of cancer patients.
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Methylcholanthrene-induced sarcoma formation in mice was found to be effectively inhibited by the intraperitoneal injection of mistletoe extract (Iscador M). Induction of sarcoma and sarcoma-induced death were inhibited completely at a concentration of 1 mg Iscador/dose. ⋯ Mistletoe extract was also found to inhibit lung metastasis induced by B16F10 melanoma cells in mice. Simultaneous administration of the Viscum album extract inhibited lung nodule formation by 92.0% and produced a 71.3% increase in life span.
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The aim of this study was to analyse whether Viscum album (mistletoe; Isorel) modulates the tumour-host relationship and whether this might be a basic mechanism of the antitumorous activity of the drug. The effects of a single intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of Isorel reduced the size of the tumour and caused abundant tumour necrosis with inflammatory response, oedema and destruction of the malignant tissue. ⋯ Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to the cytotoxic activity of the lymphocytes than the control tumour cells, particularly in the presence of the plasma of mistletoe extract-treated mice. The plasma itself, however, did not show any cytotoxic activity. These results indicate that the antitumour activity of the mistletoe drug is due to a modulation of the tumour-host relationship, mediated by direct cytotoxicity of the drug to tumour cells and/or through a potentiation of immune response by certain, as yet unidentified, growth modifying humoral factors of the host.
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The Viscum album (mistletoe) preparation Isorel is able to destroy tumour cells and to modify immune reactivity against a particular antigen in normal and in tumour-bearing animals. CBA/HZgr mice and methylcholanthrene-induced fibrosarcoma were used in these studies. A single dose of Isorel M (140 mg/kg or 1400 mg/kg body weight) significantly increased the number of plaque forming cells if applied at the time of injection of sheep red blood cells or 1 day earlier. ⋯ However, according to plaque forming cell numbers, a prolonged application of Isorel was significantly immunosuppressive in normal mice and particularly in tumour-bearing mice. It should be mentioned that the doses of Isorel used in this experiment were much higher than generally used in cancer patients. In view of the immunomodulating effects of Isorel, the monitoring of the immune response of the patients treated with mistletoe preparations is to be recommended.