• E Kunze, H Schulz, and H J Gabius.
• Center of Pathology, Faculty of Medicine, Georg-August University, Göttingen, Germany.
• J. Cancer Res. Clin. Oncol. 1998 Jan 1; 124 (2): 73-87.

AbstractExtracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic activity through their toxicity at high doses or by immunomodulation by nanogram quantities of a lectin. They are used as an unconventional therapy modality in the management of a wide range of cancer diseases, although no anticancer potential has yet been demonstrated. This prompted us to study the effect of galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with immunomodulatory properties--on chemically induced tumor development in the urinary bladder of rats and on the local cellular immune response after long-term administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was administered in a single intravesical dose (7.5 mg/kg body weight). Highly purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body weight) twice a week over the total experimental period of 15 months. The incidences of epithelial bladder tumors were 25.0% following administration of MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to be significantly different (P = 0.81). Quantitative immunohistochemistry analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin-2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer cells, granulocytes and all leukocytes expressing the leukocyte common antigen (CD45), yielded no evidence for the ability of VAA to stimulate a substantial cellular immunological reaction in the wall of the normal urinary bladder or during urothelial carcinogenesis. In conclusion, the current experimental findings provide no support at all that the galactoside-specific mistletoe lectin is capable of inhibiting chemically induced bladder carcinogenesis and triggering a local cellular immune response after prolonged application. It thus seems highly improbable that commercial mistletoe preparations or VAA will be effective in the management of human bladder cancer by a cell-mediated immunological mechanism.

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