title: Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration.
abstract: Extracts 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.
authors.affiliation: Center of Pathology, Faculty of Medicine, Georg-August University, Göttingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Kunze
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: H J
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000283:Administration, Intravesical; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D006098:Granulocytes / Q000166:cytology; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000166:cytology; D037102:Lectins / Q000008:administration & dosage / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D008770:Methylnitrosourea; D014784:Mistletoe; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D014408:Biomarkers, Tumor; D037102:Lectins; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D008770:Methylnitrosourea