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Antiproliferative activity of an aqueous mistletoe extract in human tumor cell lines and xenografts in vitro.

The in vitro antiproliferative activity of an aqueous mistletoe extract (AME) with a defined content of bioactive mistletoe lectin (ML) was tested in 25 human tumor cell lines, including 20 solid and 5 hematological malignancies and 47 human tumor xenografts. The antiproliferative activity of AME was compared to that of the standard cytotoxic agent doxorubicin (CAS 23214-92-8, adriamycin, ADR) using the sulforhodamin B, propidium iodide and soft agar colony forming assays, respectively. AME was highly cytotoxic in solid human tumors with mean IC70 values in the range of 0.17-1 ng ML/ml (2.8-17 pmol bioactive ML). On a molar basis, AME was 3 to 4 logs more potent than ADR and showed differential cytotoxicity towards tumors of the breast, small cell and non-small cell lung, prostate and renal cell cancers. AME was also highly active in hematological malignancies with steep dose response curves resulting in mean IC70 values of 0.12 ng ML/ml (2 pmol). The acute lymphoblastic leukemia cell line HL-60 was the most sensitive, the histiocytic lymphoma cell line U937 the most resistant hematological malignancy. It is important to stress that AME did not induce a biologically relevant increase of cell proliferation in any of the tumor cell lines tested. Our data suggest that AME has in vitro antitumor profiles similar to those of classical anticancer agents. Clear dose-response relationships were found in all of the performed experiments and interesting differential cytotoxicity patterns were observed. Experiments with sensitive tumor types identified in these in vitro studies are currently ongoing in order to demonstrate the anticancer activity of AME in different animal tumor models.

Animals↗

Modulation of mistletoe (Viscum album L.) lectins cytotoxicity by carbohydrates and serum glycoproteins.

Three D-galactose and/or N-acetyl-D-galactosamine specific mistletoe lectins, ML I, ML II and ML III, were purified by affinity chromatography followed by cation exchange chromatography. These lectins were toxic for Molt 4 cells in culture at concentrations in the pg/ml range, ML III being the most cytotoxic. Carbohydrates able to bind to the B-chain of these lectins inhibited their toxic activity. The digalactosides Gal beta 1,2Gal beta-allyl and Gal beta 1,3Gal beta-allyl were 60 and 30 times, respectively, more potent than D-galactose in their ability to protect the cells from the ML I cytotoxicity. N-acetyl-D-galactosamine and rho-nitrophenyl N-acetylgalactosamine protected mainly from the toxic effects of ML II and III. Protection from cytotoxicity varied in the same order as the affinity of the tested carbohydrates for lectins. Serum glycoproteins particularly haptoglobin, but also alpha 1-acid glycoprotein and transferrin, notably inhibited the cytotoxicity of the lectins. This effect was due to the binding of lectin to the sugar moiety of the glycoprotein because deglycosylated haptoglobin did not have a protective activity on Molt 4 cells. Inhibition of the cytotoxicity of lectins by serum glycoproteins explains why mistletoe extracts containing lectins can be administered to cancer patients without harmful effects.

Antineoplastic Agents↗

Roles of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in apoptosis of human monoblastic leukemia U937 cells by lectin-II isolated from Korean mistletoe.

The mitogen-activated protein kinase (MAPK) family members have been implicated in cell survival. We have previously demonstrated that cytotoxic lectin-II isolated from Korean mistletoe induces apoptotic cell death in the human monoblastic leukemia cell line, U937, via the activation of the stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK). In the present study, the roles of extracellular signal-regulated kinases (ERK1/2) and p38 MAPK in lectin-II-induced apoptosis have been investigated. Treatment of U937 cells with lectin-II resulted in apoptotic DNA fragmentation, which was preceded by the activation of ERK1/2, p38 MAPK and SAPK/JNK. This lectin-II-induced DNA fragmentation was significantly enhanced when ERK1/2 activation was selectively inhibited by PD098059. 12-O-tetradecanoylphorbol-13-acetate, which stimulates ERK activity in U937 cells, markedly reduced lectin-II-induced DNA fragmentation. Inhibition of p38 MAPK activity with p38-specific inhibitor, SB203580, partially inhibited lectin-II-induced DNA fragmentation. These results suggest that ERK1/2 and p38 MAPK may have opposite effects on cell survival in response to cytotoxic mistletoe lectin-II, which may contribute to the modulation of lectin-II-mediated cytotoxic activity.

Apoptosis↗

[Frequency of the common cold in healthy subjects during exposure to a lectin-rich and a lectin-poor mistletoe preparation in a randomized, double-blind, placebo-controlled study].

BACKGROUND/OBJECTIVE: Mistletoe preparations have immunomodulatory properties in vitro and in vivo. We wanted to investigate whether or not these properties have an effect on the frequency of the common cold in healthy subjects. PROBANDS AND METHODS: During a randomized, placebo-controlled, double-blind study 16 volunteers received the mistletoe lectin(ML)-poor preparation Iscador Pini(R) (IP), 16 the ML-rich preparation Iscador Quercus spezial(R) (IQ), and 16 placebo (physiological saline solution) twice a week subcutaneously for 12 weeks. Weekly during weeks 1-12 and finally at week 26, a careful history of common cold symptoms was taken. Because the frequency of the common cold was not the main outcome criterion in this study, the number of cases needed to treat was not adjusted to this criterion. RESULTS: The mean frequency of the common cold during the 12 weeks of injection was 1.5 in the placebo, 1.4 in the IP and 1.1 in the IQ group. During this period in 2.3 (placebo), 1.9 (IP) and 1.4 (IQ) weeks symptoms of common cold were present. The difference in favor to IQ lasted until the end of the observation period in week 26. It was, however, not significant. Leukocyte and granulocyte count as well as C-reactive protein were not different between the groups. CONCLUSIONS: The study showed a trend (p = 0.4, exact Kruskal- Wallis test) to reduced frequency and duration of the common cold in subjects who were exposed to IQ.

Adult↗

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. On Molt 4 cells, fermented Iscador also produced cytolysis but after a longer time of action. Unfermented Iscador showed a much stronger cytotoxic effect on these cells than on HTC cells. Fermented Iscador was slightly more potent than unfermented Iscador in inhibiting the growth of HTC cells, but on Molt 4 cells fermented Iscador was less active than unfermented Iscador. DNA synthesis, measured by [3H]thymidine incorporation in HTC and Molt 4 cells, was inhibited by fermented and unfermented Iscador with the same type of differences of action as on cell growth. Fermented Iscador contained a low amount of lectins, approximately 100 ng/ml, while unfermented Iscador contained about 10 times more. 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.

Animals↗

Heat shock treatment protects human HL-60 cells from apoptosis induced by lectin II isolated from Korean mistletoe, Visum album var. Coloratum.

Mistletoe lectin II (ML II) isolated from Korean mistletoe (Viscum album var. Coloratum), an effective therapeutic agent for cancers, is known to induce cell death via apoptosis. In the present study, we found the protective effect of heat shock treatment of human leukemia HL-60 cells against ML II-induced apoptosis. Exposure of HL-60 cells to ML II for 4 h resulted in apoptosis of the cells, which was evaluated by examining "DNA ladder" formation and DNA fragmentation assay. The DNA fragmentation was significantly reduced in the cells subjected to heat shock treatment by incubation at 42 degrees C for 1 h and subsequently allowed to recover for 2-16 h at 37 degrees C, prior to exposure to ML II. HL-60 cells transfected with heat shock protein (hsp) 70 gene exhibited resistance to ML II-induced apoptosis very similar to that seen when untransfected cells were heat-shocked. These results indicate that ML II-induced apoptosis in HL-60 cells is inhibited by heat shock treatment, at least in part, via a hsp 70-mediated mechanism.

Apoptosis↗

Protein kinase A or C modulates the apoptosis induced by lectin II isolated from Korean mistletoe, Viscum album var. Coloratum, in the human leukemic HL-60 cells.

Mistletoe lectins (MLs) are increasingly used as an anticancer drug in the treatment of human tumors. The cytotoxic activity of MLs against tumor cells is due to programmed cell death (apoptosis). The up- or down-regulation of protein kinase A (PKA) or C (PKC) is known to be associated with the regulation of drug-induced apoptosis. Previously, we isolated cytotoxic MLII from the extract of Korean mistletoe (Viscum album var. Coloratum) and characterized its biochemical properties. The present study was designed to investigate the role of PKA and PKC in MLII-induced apoptosis. Exposure of human leukemia HL-60 cells to various doses of MLII resulted in apoptosis. However, the treatment of these cells with dibutyl-cyclic AMP (DB-cAMP), PKA activator, or 12-O-tertadecanoyl phorbol 13-acetate (TPA), PKC activator, suppressed MLII-induced apoptosis. Furthermore, KT5720 and staurospoline, PKA and PKC inhibitors, respectively, reversed the suppression by DB-cAMP and TPA in the MLII-induced apoptosis of HL-60 cells. These results suggest that the activation of PKA or PKC was involved in the suppression of MLII-induced apoptosis in HL-60 cells. Collectively, these results indicate that activation of PKA or PKC in HL-60 cells may confer protection against MLII-induced apoptosis.

Apoptosis↗

Retrospective study of mistletoe ingestion.

BACKGROUND: There are limited data concerning accidental exposure to Phoradendron flavescens (Phoradendron serotinum, American Mistletoe). The only published reports include a review of 14 cases which revealed no symptoms and a single fatality from an intentional ingestion of an unknown amount of an elixir brewed from the berries. The risk of serious toxicity from accidental exposure to this plant appears to be minimal, yet it continues to be regarded as a dangerous plant. We reviewed charts for four years (1990-1993) from three poison centers where Phoradendron flavescens is indigenous. RESULTS: Ninety-two human cases were located. Age ranged from four months to 42 years, with a mean of six years (SD 8.8) and median of two years. There were 14 symptomatic cases of which 11 were determined to be related to mistletoe exposure. There were six gastrointestinal upset, two mild drowsiness, one eye irritation, one ataxia (21 months), one seizure (13 months). Treatments included gastrointestinal decontamination in 54 patients (59%), ocular irrigation in one and IV benzodiazepine in one. Decontamination did not appear to affect outcome. Amount ingested ranged from one berry or leaf to more than 20 berries or five leaves. In cases with a known amount ingested, eight of ten cases with > or = 5 berries remained symptom free. In the 11 cases with leaf-only ingestion (range 1-5 leaves), three patients had gastrointestinal upset. The one case with five leaves ingested remained asymptomatic. The infant with seizures was an unwitnessed exposure, found with both berries and leaves in the crib. No arrhythmias or cardiovascular changes were reported in any case. All symptomatic cases had onset of symptoms in < or = 6 hours. DISCUSSION: Symptoms are infrequent and in all but one case would not require direct medical supervision. Seizures have not previously been reported with Phoradendron flavescens exposure. CONCLUSION: Symptoms from Phoradendron flavescens exposure are infrequent, even with ingestion of 5-20 berries or 1-5 leaves, but may include seizures. Cardiovascular effects were not seen.

Adolescent↗

Viscotoxin-free aqueous extracts from European mistletoe (Viscum album L.) stimulate activity of human granulocytes.

BACKGROUND: Extracts from European mistletoe (Viscum album L., VAL) are used for complementary cancer treatment. Viscotoxins (VT) and whole plant extracts with high amounts of the VT have been shown to stimulate functional activity of granulocytes. MATERIALS AND METHODS: We stimulated neutrophils from healthy donors in vitro with aqueous VT-free VAL extracts and mistletoe lectins (ML) in the presence of E.coli and studied phagocytosis (via incorporation of FITC-labelled E.coli) and respiratory burst (via oxidation of dihydrorhodamine 123 to rhodamine 123) by flow cytometry. RESULTS: The VT-free VAL extract significantly stimulated granulocyte activity, and this effect correlated with the content of the ML, although the ML exerted no influence at relevant concentrations. Co-incubation of the cells with VAL in the presence of VT further increased granulocyte response. CONCLUSIONS: From these data it is suggested that (1) a non-VT non-ML component of the VAL extracts activated granulocytes and (2) different activation pathways may be involved in the stimulation by the whole plant extract and the VT.

Granulocytes↗

Toxic proteins from European mistletoe (Viscum album L.): increase of intracellular IL-4 but decrease of IFN-gamma in apoptotic cells.

BACKGROUND: Mistletoe lectins (ML), the major biologically active components of mistletoe extracts, which are used for adjuvant cancer therapy, induce apoptosis in lymphocytes and tumor cells. In addition, ML at toxic concentrations induce the release of cytokines, but it remains unclear as to whether dying or activated cells are responsible. MATERIALS AND METHODS: By flow cytometry, expression of IFN-gamma, IL-4, apoptosis marker Apo2.7 and anti-apoptotic Bcl-2 proteins were analyzed in response to ML or viscotoxins (VT) in PBMC from controls and plasmocytoma cells (U-266). RESULTS: While ML inhibited PMA/Ca-ionophore/monensin co-stimulated IFN-gamma production, they increased IL-4 expression in CD8+ and CD4+ T-cells. Thereby, IL-4 was mainly expressed in apoptotic cells with a low level of Bcl-2 proteins. In contrast, the cell membrane permeabilising VT induced complete loss of Bcl-2 proteins but did not stimulate IL-4 production within 24 hours, indicating that IL-4 expression is related to apoptosis but not to necrosis. CONCLUSION: Despite the role of IL-4 during activation of type2 T-helper cells, IL-4 expression may play an important yet undefined role during apoptosis of normal and tumor cells.

Apoptosis↗

Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study.

CONTEXT: In anthroposophical medicine, total extracts of Viscum album (mistletoe) have been developed to treat cancer patients. The oldest such product is Iscador. Although Iscador is regarded as a complementary cancer therapy, it is the most commonly used oncological drug in Germany. OBJECTIVE: To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon, rectum, or stomach; breast carcinoma with or without axillary or remote metastases; or small cell or non-small-cell bronchogenic carcinoma; and to explore synergies between Iscador treatment and psychosomatic self-regulation. DESIGN: Prospective nonrandomized and randomized matched-pair studies nested within a cohort study. SETTING: General community in Germany. PARTICIPANTS: 10,226 cancer patients involved in a prospective long-term epidemiological cohort study, including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product (control patients). INTERVENTION: Iscador. MAIN OUTCOME MEASURE: Survival time. RESULTS: In the nonrandomized matched-pair study, survival time of patients treated with Iscador was longer for all types of cancer studied. In the pool of 396 matched pairs, mean survival time in the Iscador groups (4.23 years) was roughly 40% longer than in the control groups (3.05 years; P < .001). Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation (56% relative to control group; P = .03) than for patients with poor self-regulation. Results of the 2 randomized matched-pair studies largely confirmed the results of the non-randomized studies. CONCLUSION: Iscador treatment can achieve a clinically relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation.

Antineoplastic Agents, Phytogenic↗

No evidence of stimulation of human tumor cell proliferation by a standardized aqueous mistletoe extract in vitro.

The in vitro antiproliferative or stimulatory activity of an aqueous mistletoe extract (AME) with a defined content of bioactive mistletoe lectin (ML) was investigated in 6 human tumor cell lines, including two melanomas and leiomyosarcomas, each of which had previously been reported to show evidence of growth stimulation if treated with low concentrations of isolated ML. The effects of AME were compared to that of the standard cytotoxic agent adriamycin (ADR) using the well established propidium iodide and sulforhodamin B proliferation assays. The AME concentrations used ranged from 0.5 pg to 5 ng (0.82 fMol-85 pM) bioactive ML/ml in melanoma (HT-144, SK-MEL-28) and leiomyosarcoma (SK-MLS-1, S-UT-1B) cell lines and from 0.1-100 ng ML/ml (1.7 pM-1.7 nM) in MCF-7 breast cancer and SW620 colon carcinoma cell lines, respectively. The influence of AME on cell growth was determined at various time-points from 24 hours to 6 days of exposure. We found a time- and cell line-dependent inhibition of tumor cell growth, but no reproducible stimulation of tumor cell proliferation. Inhibitory concentrations 50% (IC50) for e.g. the SK-MEL-28 melanoma cell line, decreased from 4.1 ng ML/ml at 24 hours to 0.16 ng ML/ml at 72 hours and 0.18 ng ML/ml at 5 days. Our data clearly demonstrate that, by applying scientifically valid methods and procedures, the standardized AME did not stimulate tumor cell proliferation but showed time- and concentration-dependent antiproliferative effects.

Cell Division↗

Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.

Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the "Intention to treat principle". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.

Antineoplastic Agents↗

Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations.

BACKGROUND: Medulloblastoma constitute more than 20% of all paediatric brain tumours and are the most common malignant brain tumours in children. Adjuvant chemotherapy has seen a strong increase in the use of complementary medicine for cancer treatment. Evidence for cytotoxic and apoptotic effects of Viscum album (Mistletoe) in vitro is available, however, no data concerning paediatric tumours, especially paediatric brain tumours, has been provided so far. MATERIALS AND METHODS: In order to compare the receptiveness of medulloblastoma cells to different Viscum album preparations, in vitro cytotoxic effects of eight Viscum album extracts on four different paediatric medulloblastoma cell lines were analysed by MTT-Tests. Lectin contents of the extracts were determined to correlate them with the mitochondrial activity of mistletoe-treated cells. Flowcytometric analyses with Annexin V-FITC staining were carried out to quantify the amount of apoptotic cells compared to necrotic and viable cells. RESULTS: Data obtained with the medulloblastoma cell lines, Daoy, D342, D425 and UW-288-2, treated with Viscum album preparations from eight dissimilar host trees (Iscucin Abietis, Pini, Populi, Mali, Salicis, Crataegi, Quercus and Tiliae), indicated a significant growth-inhibition of all cell lines, yet the cell susceptibility was dissimilar against the different extracts. The decrease in mitochondrial activity and increase in apoptosis correlated with the lectin content of the used preparation in a dose-dependent manner. CONCLUSION: These in vitro results show that paediatric medulloblastoma cells respond to Viscum album preparations, by undergoing cell death through apoptosis and that this growth-inhibition correlates with the lectin content of the used preparation.

Annexin A5↗

Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model.

The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was examined by established assays towards the human ductal breast carcinoma cell line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p < 0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In vivo experiments on the antitumor activity of ME-A and ME-M were performed in a BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were intratumorally administered according to an application schedule which was found to be optimal concerning dosage and time of administration. Standardized intratumoral application of ME-A and ME-M induced a significantly (p < 0.05) decreased tumor weight in experimental mice. Histological investigations were performed comprising analysis of mitosis and proliferation rates (Ki67 expression), as well as necrosis and apoptosis induction (ssDNA detection). As compared to tumors of control mice with intratumoral phosphate-buffered saline (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased cell proliferation rate, as well as an increased cell necrosis and apoptosis rate. Standardized mistletoe extracts, interfering with defined tumor cell functions, e.g., proliferation, necrosis and apoptosis, may have an impact on local cancer treatment.

Animals↗

Internalization and action of an immunotoxin containing mistletoe lectin A-chain.

An immunotoxin consisting of the enzymatically active A-chain of mistletoe lectin I and a monoclonal antibody against a surface protein on mouse leukemia L1210V cells was found to inhibit protein synthesis in these cells as efficiently as the native mistletoe toxin. The immunotoxin was somewhat more slowly endocytosed than the native toxin, but in both cases the endocytic uptake continued under conditions in which uptake from clathrin-coated pits was inhibited by mild acidification of the cytosol. This indicates that the toxin and the immunotoxin were at least partially internalized by a non-clathrin-dependent uptake mechanism and that uptake by this pathway is responsible for most of the toxic effect on the cells. The results indicate that efficient immunotoxins can be made with antibodies against cell surface epitopes that are endocytosed by a mechanism not involving clathrin-coated pits.

Animals↗

[Helixor--mistletoe preparation for cancer therapy. Documentation No. 19].

Helixor is an aqueous cold extract from fresh mistletoe, obtained from fir, pine and apple trees. A number of components with different possible effects were isolated: lectins, viscotoxins, alkaloids, etc. "Oncological therapy" and "stimulation of the bone marrow" are given as the main fields of indication. Pregnancy, hyperthyroidism and intolerances are given as contraindications. Depending on the type and the stage of the tumour, treatment based on a specific rhythmic schedule should be carried out for a period ranging from five years to a lifetime. A 7-ampoule pack costs 37 to 44 DM. Local inflammatory reactions occur as side effects. Fever is desirable. Helixor was developed by the Section for Leukemia and Cancer Therapy of the Gemein-schaft Fischermühle e. V. in Rosenfeld, FRG, and has been used since about 1968. It is produced and distributed by Helixor Heilmittel GmbH & Co. The origin of anticancer treatment with Helixor, a mistletoe preparation, is the anthroposophical medicine. In addition, Helixor supposedly bridges the dramatic gap between conventional and natural treatment of cancer in that it exerts both a selective cancerostatic and an immunostimulatory effect. Hardly any research has been done on the pharmacodynamics, the pharmacokinetics and the toxicity of the total extract Helixor. In vitro studies reveal a cytostatic effect on individual cell lines; animal experiments with freshly pressed juice are contradictory. Specific effects of Helixor on the immune system and its actual bearing on the tumour process have so far not been unequivocally elucidated. The three clinical-historical comparative studies contain methodological errors. They do not provide evidence of the clinical efficacy against tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents, Phytogenic↗

[Iscucin--mistletoe preparations for the pre- and postoperative treatment of malignancies. Documentation No. 21].

Iscucin-Viscum preparations contain mistletoe from eight different host-trees and are produced according to a particular 'rhythmic' procedure and additionally 'potentialized'. Sterilization should be achieved by the addition of oligodynamic silver. The indications given are: precancerous conditions, postoperative tumour prevention, operable tumours, and inoperable tumours. Each of the eight preparations (according to host-tree) has its own list of indications. Iscucin is supposed to be injected close to the tumour between 5 and 7 p. m.; the dosage and the frequency depend on body temperature. The annual costs of Iscucin treatment are DM 140.- to 280.-, not including doctor's visits, homeopathic drugs and special diet. Koehler began to develop Iscucin in 1958 on the basis of a personal communication of Steiner made in 1924. It is produced and distributed by Wala-Heilmittel GmbH, Eckwälden. Most Wala publications have been written by H. H. Vogel, the medical advisor of Wala. Vogel combines Fromme's mesenchymal theories with the anthroposophical ideas on carcinoma development in that he designates the mesenchyma as the organic vehicle of the 'ethereal body' (Atherleib). Carcinomas develop on depletion of the mesenchymal forces; mistletoe, on the other hand, activates the mesenchyma. No preclinical or clinical investigations are available. However, the performance of controlled clinical studies is hardly possible, since the supportive measures considered to be essential cannot be applied according to a specific schedule. Iscucin is not registered in Switzerland at the IKS.

Antineoplastic Agents, Phytogenic↗