Oncology
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Iscador, a mistletoe preparation widely used in cancer chemotherapy, was found to contain a toxic component which is structurally and functionally closely related to viscumin. When antiviscumin was present in the medium, Vero cells were strongly, but not completely protected against Iscador. ⋯ The main cytotoxic protein in Iscador was retained on a desialylated fetuin column and on an antiviscumin column. This material was found to have a molecular weight close to, but not identical to, that of viscumin.
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Over 160 cases of pleura carcinosis were treated systematically by local intrapleural instillation of Iscador, and the results were documented by cytomorphological examination of the punctate. The results show that, under these conditions, Iscador has two distinct activities, i.e. cytotoxic activity and immunostimulating activity.
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Comparative Study
Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells.
The bacterially fermented mistletoe preparation Iscador, used in cancer therapy for 30 years, and the recently prepared unfermented preparation, have been tested on rat hepatoma tissue culture (HTC) cells and human leukemia Molt 4 cells. As observed by phase-contrast microscopy, treatment of HTC cells with fermented or unfermented Iscador, at a concentration corresponding to 1 mg of fresh plant per milliliter culture, led to rapid lysis of cellular membranes. At a lower concentration, 0.1 mg/ml, unfermented Iscador led to the formation of polynucleated cells. ⋯ A purified mistletoe lectin produced effects on HTC and Molt 4 cells similar to those of unfermented preparations. HTC cells were 100 times less sensitive to this lectin than Molt 4 cells. These results are discussed in relation to the known biological effects of lectins.
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The newly isolated phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and viscotoxins were selected for a standardization of mistletoe extracts and drug preparation. The phenylpropanoids found in all alcoholic and aqueous extracts were suitable for an HPLC fingerprint analysis, and for quantitative determination. ⋯ As shown by the isoelectric focussing method, Iscador and fermented mistletoe extracts contain only the mistletoe lectins ML II/III, whereas the proteins of the ML I complex are missing. For identification and quantitative determination of viscotoxins, an HPLC method was designed.
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The relative efficacy of hormonal, chemical, or combined therapy was investigated in a prostate cancer animal model. 96 Copenhagen-Fischer hybrid rats were implanted with equal-sized fragments of the Dunning H strain transplantable prostatic adenocarcinoma. These animals were randomly assigned to 1 of 6 treatment groups: (1) control, (2) testosterone, (3) testosterone followed by cyclophosphamide, (4) cyclophosphamide, (5) orchiectomy or (6) orchiectomy followed by cyclophosphamide. Animals in the control group had the shortest survival, fastest tumor growth rate, and largest tumor size. ⋯ Testosterone administered prior to cyclophosphamide eliminated and shortened survival from cyclophosphamide. The best overall results were obtained by orchiectomy alone, orchiectomy plus cyclophosphamide, and testosterone plus cyclophosphamide. Although chemotherapy alone was effective in shrinking tumor size, it was highly toxic.