Therapeutic effects of the MLs were inconsistent and not very impressive in the reviewed experiments. However, in other tumour types, MLs have also shown substantial growth-inhibiting effects (e.g. [154–157]). Interestingly, in two experiments, the application of VAE-activated macrophages in mice not directly treated with VAE also showed tumour-growth inhibiting effects, while the application of non-activated macrophages had no effects . Similarly in melanoma, the application of VAE-activated splenocytes inhibited
metastasis [158, 159]. In general, the predictive reliability of the preclinical studies for clinical application is #OSI-906 supplier randurls[1|1|,|CHEM1|]# fairly limited in most instances. Clinical cancer disease is insufficiently mimicked by animal models, with major differences regarding age, general condition, co-morbidity, invasiveness, metastases, antigenicity, immune system etc. The results of preclinical screening, especially for treatment of solid tumours, have therefore been largely disappointing. The models currently regarded as best for cytotoxic substances use patient-derived tumours that grow subcutaneously or orthotopically in nude mice, as in several cases reviewed here. Immuno-active substances FK228 chemical structure may however still be insufficiently assessed in immune-deficient animals, as the main components of the immune system
are missing (nude mice, for instance, cannot generate mature T-lymphocytes). Nevertheless, these preclinical experiments can provide important additional information for detecting the possible anti-cancer effects of medicinal
plants, their active compounds, their mode of action and potential risks [20, 160–162]. Safety aspects Mistletoe therapy was well tolerated in the reviewed studies. Mild flu-like symptoms and local reactions at the injections sites are frequent, dose-dependent and self-limited. Allergic reactions can occur, and a few case reports of anaphylactic reactions exist [163–166]. A phase I study, conducted at the NCCAM/NCI, investigated safety, toxicity and drug interactions between VAE and gemcitabine see more  and reported good tolerability, with neither dose-limiting toxicity of the VAE nor any effects on the plasma concentration of gemcitabine . Combination of VAE with chemotherapy or radiotherapy did not negatively influence remission rate in clinical and in animal studies [56, 63, 118]. A higher prevalence of depression in VAE-treated patients in one study was observed in raw data of a self-selected population, without adjustment of baseline imbalances. This difference can be ascribed to variations in the patient population; for instance, they differed markedly in the prevalence of hormone treatment. No toxicity was observed in animal experiments.