Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mistletoe”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1986

Assessing mistletoe toxicity.

To assess the potential toxicity of mistletoe ingestion, data were collected on 14 cases of ingestion of one to three berries or one or two leaves of American mistletoe (Phoradendron sp) from 1982 to 1985. Eleven patients ingested berries and three ingested leaves; none became symptomatic. Nine patients were observed at home without intervention except poison center telephone follow-up. Five had induced emesis, including two who were referred to emergency departments for evaluation, where no findings other than ipecac-induced vomiting were noted. Also reviewed were data on a total of 318 cases of mistletoe ingestion reported to the Food and Drug Administration Poison Control case reporting system between 1978 and 1983 (n = 177) and the American Association of Poison Control Centers national data collection system (n = 141) in 1984. The majority remained asymptomatic and no deaths were recorded. These data allow the conclusion that ingestion of one to three mistletoe berries or one or two leaves is unlikely to produce serious toxicity.

Adolescent↗
PubMed1998

Cytotoxicity of heat-treated Korean mistletoe.

The cytotoxic effects of preparations of Korean mistletoe (Viscum album L. var. coloratum Ohwi) on non-tumorigenic A31 cells and tumorigenic MSV cells were investigated. While the aqueous extract from Korean mistletoe (<8 microg/ml) showed strong cytotoxicity on both cell lines, the heat-treated extract was much less cytotoxic with TD50 values of above 300 microg/ml. The heat-treated extract showed a growth-enhancing effect on non-tumorigenic cells and a cytotoxic effect on tumorigenic cells. The alkaloids fraction, which was isolated from the crude extract, was not cytotoxic to non-tumorigenic A31 cells up to 550 microg/ml, but was cytotoxic to tumorigenic MSV cells at 138 microg/ml. Heat treatment did not change the cytotoxic effects of the alkaloids fraction, indicating that the selective cytotoxicity of the heat-treated mistletoe extract on tumorigenic MSV cells might be due to its alkaloids. In order to study the changes in the cytotoxicity of fermented Korean mistletoe, the crude and heat-treated extracts were inoculated with Lactobacillus plantarum. During 7 days of fermentation, the cytotoxicity of the fermented heat-treated extract was increased while that of the fermented crude extract was not changed significantly.

Alkaloids↗
PubMed1997

American mistletoe exposures.

American mistletoe is generally considered to be extremely toxic. Although there are no data to support this contention, both the lay public and medical professionals often respond very aggressively after ingestion of any portion of this plant. To determine if American mistletoe is deserving of this reputation, the outcomes of 1,754 exposures to this plant were examined. All mistletoe data extracted from the American Association of Poison Control Centers national data collection system for the period of 1985 to 1992 were analyzed according to patient age, gastrointestinal decontamination therapy, patient outcome, and geographic region of the exposure. Pediatric exposures accounted for 92.1% of the cases, and 94.7% of the reported cases were accidental exposures. Of all cases, 99.2% had an outcome associated with no morbidity, and there were no fatalities. Apparently, patient outcome was not influenced by the use of gastrointestinal decontamination techniques-96.2% of treated patients remained asymptomatic versus 96.3% of patients who received no therapy. The accidental ingestion of American mistletoe is not associated with profound toxicity.

Humans↗
PubMed2000

Induction of apoptosis by mistletoe lectin I and its subunits. No evidence for cytotoxic effects caused by isolated A- and B-chains.

Type II ribosome inactivating proteins (RIP II) are generally known to induce apoptosis in human cells by the inhibition of protein biosynthesis. Recent data from mistletoe RIP II proteins (eg. mistletoe lectin I; ML1) suggest an additional mode of apoptosis induction through the binding of their lectin part to certain cell surface receptors as is known for some human galectins. In order to clarify this possibility, we used highly sensitive flow cytometric apoptosis assays and mistletoe hololectin subunits of proven purity to show that neither human lymphocytes nor Molt-4 cells undergo apoptosis after treatment with isolated lectin-type B-chains. In contrast to earlier investigations, only the hololectin was able to induce apoptosis in these assays. We conclude that direct apoptosis induction by mistletoe lectins occurs only after uptake of the molecules into the cell due to the action of the ribosome inactivating A-chain.

Apoptosis↗
PubMed1999

Characterization of recombinant and plant-derived mistletoe lectin and their B-chains.

Mistletoe lectin I (pML) and its isoforms ML II and III constitute the active principle in extract preparations from mistletoe, commonly used as immunomodulator in adjuvant tumour therapy. The heterodimeric disulfide-linked cytotoxic protein is classified as type II ribosome inactivating protein (RIP). Recently, the sequence coding for the mistletoe lectin prepro-protein was identified and the existence of a single intron-free gene was shown [Eck, J., Langer, M., Möckel, B., Baur, A., Rothe, M., Zinke, H. & Lentzen, H. (1999) Eur. J. Biochem. 264, 775-784]. The aim of this study was to prepare pure and homogeneous rMLB-chain as well as rML heterodimer for studying the carbohydrate binding specificity of recombinant versus natural protein and its contribution to the observed cytotoxic effect. Expression in E. coli resulted in the production of insoluble protein (inclusion bodies). A procedure for generating correctly folded, biochemically and biologically active rMLB was established starting from the insoluble single chain. Carbohydrate binding and specificity of pMLB and rMLB were analysed by a competitive enzyme linked lectin assay (ELLA). Asialofetuin was able to compete with binding of both chains (50% at 0.8 microM). The specificity of the B-chains to lactose was more distinct with halfmaximal competition at 4.9 mM (pMLB) and > 90 mM (rMLB), respectively. Furthermore, in a coassociation process rMLA- and rMLB inclusion bodies were associated in one step by defined dilution yielding active rML-heterodimer. The activities of recombinant (rML) and plant derived mistletoe lectin (pML) were compared. Cytotoxicity was determined using MOLT-4 cells and enzymatic rRNA N-glycosidase activity was measured in a coupled transcription/translation assay. The IC50 values of the two heterodimers were similar in both assays; rMLB-chain did not show any cytotoxic effect. In the ELLA with lactose as a competitor 50% competition of binding to asialofetuin was achieved at 1.6 mM (rML) and 1.8 mM (pML). Hence, using three different assays we found no significant differences between the recombinant protein and the glycosylated form of ML. Comparing the biological activities of the single chains with those of the heterodimer we conclude, that both, lectin activity and the rRNA N-glycosidase activity, are prerequisites for the cytotoxic effects on target cells.

Asialoglycoproteins↗
PubMed2002

Mistletoe and cancer: controversies and perspectives.

Extracts and preparations from the tree parasitic plant mistletoe (Viscum album L.) have been used in the treatment of cancer for decades. Numerous preclinical and in vitro studies have reported immunostimulatory, cytotoxic, and proapoptotic effects. Translation of these effects into clinical response continues to pose a problem. While a number of clinical studies have found improvement in quality of life (QOL), data on the efficacy of mistletoe to prolong survival are conflicting and of variable quality. Clinical trial data regarding the toxicity and pharmacokinetics of mistletoe components with known in vitro or preclinical activity are lacking. Mistletoe is a widely used form of complementary and alternative medicine (CAM) for cancer treatment, and research into its use poses the challenges of translation of preclinical data into demonstrable clinical efficacy and investigating CAM approaches as a component of complex cancer treatment systems.

Animals↗
PubMed1999

Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks.

Subcutaneous injections of fermented and unfermented aqueous extracts of Viscum album L. result in a local inflammatory reaction at the injection site. In this trial, the symptoms associated with this local reaction were investigated. Furthermore the occurrence of local reactions was tried to correlate with an increase in CD3/25- and CD8/38-positive lymphocyte counts, with eosinophilic granulocyte numbers, and with the formation of mistletoe lectin antibodies. Included in the trial were 30 HIV-antibody-positive patients and 17 healthy non-smokers, aged 24-51 years. The CD4 cell count in the HIV-negative subjects was > 800/microliter, compared with 200-600/microliter in the HIV-positive patients. All study participants had a Karnofsky score > or = 70. The trial subjects were observed over a period of 18 weeks. With escalation of the dose of a fermented and unfermented extract of Viscum album L. (Iscador Qu Spezial and Viscum album QuFrF), there was an increase in local reactions. Erythema at the injection site was the most frequently reported symptom. Between the doses and the symptoms induration, swelling and pruritus were marked correlations. Effects of the application of mistletoe extracts on the immune system were demonstrated by an increase in CD3/25-positive lymphocyte counts and antibodies against mistletoe-lectins. There were no changes in eosinophilic granulocytes or CD8/38-positive lymphocyte populations. For evaluation of the therapeutic applications of mistletoe extracts in HIV-positive patients it is advisable to assess primarily activation of CD3-positive lymphocytes and the patient response on the basis of the local reaction. The local inflammatory reaction at the injection site is desirable and well tolerated if the reaction is smaller than 5 cm in diameter.

Adjuvants, Immunologic↗
PubMed1998

[Subcutaneous manifestations of a centrocytic non-Hodgkin lymphoma at the injection site of a mistletoe preparation].

HISTORY AND CLINICAL FINDINGS: A 73-year-old man, first diagnosed as having centrocytic Non-Hodgkin lymphoma 5 years previously, presented with subcutaneous nodes of the abdominal wall at precisely the sites of previous regular injections of a mistletoe preparation. These nodes had first appeared 5 weeks after the first injection. Injections were stopped and he reported to the out-patient clinic. Except for the visible and easily nodes in the anterior wall no other subcutaneous nodes were palpated. Prominent cervical lymphomas and swelling of the epicranial aponeurosis and lower lip had, according to the patient, been present for some time. INVESTIGATIONS: There was a T-lymphocytopenia, lactate dehydrogenase activity was raised to 255 U/l. The subcutaneous nodes in the anterior abdominal wall were also demonstrated by ultrasound. Computed tomography showed them as having the density of connective tissue and being up to 5 cm in diameter. The excised nodes histologically revealed to be infiltrations by the centrocytic lymphoma. TREATMENT AND COURSE: Once the mistletoe injections had been discontinued no further subcutaneous infiltrates were seen despite the progression of the lymphoma. Six weeks later the patient died of bilateral pneumonia. CONCLUSION: There are pointers that high concentrations of mistletoe preparations subcutaneously injected can have a growth-promoting action on cells of a centrocytic lymphoma. As part of a leukaemic "wash-out", these cells reach the subcutaneous tissue. This proliferative stimulus may have been mediated by a high local concentration of interleukin-6 liberated from the skin by mistletoe lectins.

Abdominal Muscles↗
PubMed1997

Mistletoe extract-induced effects on immunocompetent cells: in vitro studies.

Cytotoxic as well as immunomodulatory effects of mistletoe extracts and their components have been described and seem to depend upon the host tree, the manufacturing process and the composition of the different components present in the extracts. In vitro studies showed that a fermented mistletoe extract derived from Viscum album L. grown on pine trees was less cytotoxic to peripheral blood mononuclear cells (PBMC) than other preparations. This finding could be related to its very low content of mistletoe lectins. Furthermore, this extract stimulated PBMC from healthy and especially allergic donors who had never received any mistletoe treatment. By analysing these in vitro reactions, an involvement of CD4+ T helper cells and CD14+ monocytes/macrophages was observed, suggesting an interaction of the specific and nonspecific immune system. In the supernatants of stimulated PBMC from healthy individuals, type-1 (interferon-gamma and interleukin-2) and type-2 (interleukin-4 and interleukin-5) associated cytokines were detected in about 20%. In patients with colorectal tumours, however, reduced frequency, suggesting a functional impairment of certain immunocompetent cells in these patients. These studies may help to evaluate properties of the natural and the specific immune system.

Adjuvants, Immunologic↗
PubMed1997

Mistletoe therapy for human cancer: the role of the natural killer cells.

Extracts produced from Viscum album L. (mistletoe) as well as certain isolated components are able to stimulate different functions of the immune system. The natural killer cells have been suggested as one of the candidates for direct tumour cell destruction. These cells are defined by their ability to mediate non-major histocompatibility complex (MHC) restricted cytotoxicity without prior sensitization against a specific antigen. However, their effectiveness in tumor defence in vivo is unclear. In general, natural killer cells are unable to lyse fresh autologous tumour cells in vitro unless activated by interleukin-2-preincubation. The results of clinical studies are contradictory, but there is evidence that they may contribute to the prevention of the development of recidives and metastases. In this regard it is interesting that mistletoe extracts are able to stimulate natural killer cell-mediated cytotoxicity in vitro directly as well as indirectly in a cytokine-like manner, with the active components being carbohydrates rather than lectins. Clinical application of mistletoe extracts or isolated lectins is reported to induce augmentation of both number and activity of natural killer cells in peripheral blood in a dose-dependent manner; however, non-responders also have been described. In future work it has to be clarified whether a mistletoe-derived modulation of the natural killer system is of benefit in the tumour defence of cancer patients.

Adjuvants, Immunologic↗
PubMed1997

Clinical relevance of immunoactive mistletoe lectin-I.

Recent investigations have shown that defined, non-toxic doses of the galactoside-specific mistletoe lectin (mistletoe lectin-I, a constituent of clinically approved plant extracts) have immunomodulatory potencies. The obvious ability of certain lectins (e.g. mistletoe lectin-I) to activate (non)-specific defence mechanisms supports the assumption that lectin-carbohydrate interactions may induce clinically beneficial immunomodulation. Initial clinical trials were promising and currently prospectively randomized multicentre trials are being performed to evaluate the ability of complementary mistletoe lectin-I treatment to reduce the rate of tumor recurrences and metastases, to improve the overall survival as well as the quality of life and to exert immunoprotection in cancer patients under tumor destructive therapy.

Adjuvants, Immunologic↗
PubMed2006

Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador).

BACKGROUND: Mistletoe preparations such as Iscador (Weleda, Schwäbisch Gmünd, Germany) are commonly used in complementary and alternative / anthroposophic medicine for many cancer indications, particularly for solid cancers. Efficacy of this complementary therapy is still controversial. OBJECTIVE: Does long-term therapy with Iscador show any effect on survival, tumor progression and psychosomatic self-regulation of patients with breast cancer? PATIENTS AND METHODS: Prospective recruitment and long-term follow-up of two controlled cohort studies: (1) Randomized matched-pair study (38 pairs): breast cancer patients without any recurrences or metastases and no mistletoe therapy were matched for prognostic factors. By pairwise random allocation, one of the patients was suggested mistletoe therapy to be applied by the attending physician. (2) Non-randomized matched-pair study (84 pairs): breast cancer patients without recurrences or metastases that already received mistletoe therapy were matched to control patients without Iscador therapy. RESULTS: For overall survival, the nonrandomized study shows significant effects in favor of Iscador therapy: hazard ratio HR estimate and 95% confidence interval CI: 0.43 (0.27-0.68). The effect of long-term Iscador therapy on tumor progression as measured by the time to local recurrences, lymphatic or distant metastases in breast cancer patients without any such events at first diagnosis, is in most cases significant in favor of the Iscador group, in the randomized as well as in the non-randomized study. Psychosomatic self-regulation in the Iscador group improves significantly within 12 months compared with the control group in the randomized as well as in the non-randomized study: estimate of the median difference and 95% CI: 0.35 (0.05-0.60), respectively 0.20 (0-0.35). CONCLUSION: Iscador shows a clinically relevant effect on breast tumor progression as measured by overall survival as well as by the time to recurrences, lymphatic or distant metastases. In the short term, psychosomatic self-regulation increases more markedly under complementary Iscador therapy than under conventional therapy alone.

Antineoplastic Agents, Phytogenic↗
PubMed1986

Mistletoe lectins and their A and B chains.

Mistletoe lectins are of high biological activity. The mistletoe lectin I (ML I) is a naturally occurring conjugate of an enzyme (A chain) and a lectin (B chain). Its cytotoxicity is caused by inhibiting the protein synthesis on the ribosomal level. Prominent properties of the A chain are mitogenicity and inhibition of the protein synthesis in cell-free systems. The A chain is also a candidate for the construction of immunotoxins. The B chain as well as the intact lectins activate macrophages and release lymphocytes. They both inhibit the allergen-induced histamine release from leukocytes and the collagen-induced serotonin release from platelets. It cannot be excluded that the combination of selectively cytotoxic and immunopotentiating properties of mistletoe lectins and their chains are decisive for the therapeutic effects of mistletoe preparations.

Animals↗
PubMed2006

Mistletoe lectin (Viscum album coloratum) modulates proliferation and cytokine expressions in murine splenocytes.

It is well documented that an extract of European mistletoe has a variety of biological effects, such as the stimulation of cytokine production from immune cells, and additional immunoadjuvant activities. While the European mistletoe has been studied intensively, we know less about Korean mistletoe as a therapeutic plant, especially as a possible immunomodulating drug. This study will investigated the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on murine splenocytes to investigate whether VCA acts as an immunomodulator, which could lead to improved immune responses in these cells. The results showed that VCA inhibited cell proliferation at higher concentrations (at 1-8 ng/ml) and enhanced cell proliferation at lower concentrations (at 4-32 pg/ml). Further studies were carried out to determine if the proproliferative or anti-proliferative activity exhibited by VCA was correlated with cytokine secretion. Consequently, interferon (IFN)-gamma secretion was decreased in concanavalin A (ConA)-stimulated murine splenocytes by VCA (4-64 ng/ml), but there was no change in IL-4 levels. This suggests that VCA has the ability to modulate murine splenocyte proliferation and can possibly act on the balance of Th1/Th2 cellular immune responses.

Animals↗
PubMedDate not supplied

Intracellular expression of IL-4 and inhibition of IFN-gamma by extracts from European mistletoe is related to induction of apoptosis.

BACKGROUND: Extracts from European mistletoe are used for adjuvant cancer treatment. Their influence on the intracellular expression of cytokines of the T-helper cells type-1 (Th1; IFN-gamma) or type-2 (Th2; IL-4) is still unknown. MATERIALS AND METHODS: Lymphocytes from controls were incubated with mistletoe extracts (ME) and mistletoe lectins (ML) for 24 hours and co-stimulated with PMA/Ca-ionophore/monensin during the last 6 hours. Apoptosis and intracellular cytokine expression were detected by flow cytometry, the cytokine release into the supernatants by ELISA. RESULTS: ME and ML significantly inhibited intracellular expression of IFN-gamma but stimulated IL-4. Thereby, IL-4 was mainly expressed in apoptotic (Apo2.7+) cells. However, IFN-gamma secretion into the supernatants of the cells was dose-dependently inhibited by ME and ML, while IL-4 was not detected at all. CONCLUSION: The intracellular expression of the 'Th2-cytokine' IL-4 in ME- and ML-exposed cells may not be related to a typical Th2-response but rather to cell death. This effect might be of great relevance e.g. after intratumoural injection of the mistletoe extracts and, in general, for the inhibition of an inflammatory response during apoptosis.

Apoptosis↗
PubMedDate not supplied

Antitumoral effects of an intravesically applied aqueous mistletoe extract on urinary bladder carcinoma MB49 in mice.

The objective of the present study was to investigate the effects of a locally applied aqueous mistletoe extract (AME) on the growth of urinary bladder carcinoma MB49 in an orthotopic murine model. On day 1, a total of 4 x 10(4) tumor cells was implanted into the bladder of female C57BL/6J mice. The animals were then randomly allocated to three groups of 13 mice each. From day 11 onwards, AME was given intravesically 3 days a week for 4 consecutive weeks at concentrations related to 30 or 300 ng bioactive mistletoe lectin (ML)/ml. The animals received a total volume of 0.1 ml. In the control group, 39% of the mice survived to the end of the scheduled study period in comparison to 69% and 85% in the groups treated with 30 or 300 ng ML/ml, respectively. At necropsy, 80% of the surviving control animals showed a visible solid bladder tumor, whereas only 56% and 18% had tumors in the treated groups. In both cases, the differences were statistically significant at the high concentration in comparison to controls (p < 0.05). A non-significant effect was observed regarding the formation of multiple metastases (40% in controls vs 33% and 18% in the treated groups). From the results, it was concluded that under the conditions described, AME shows antitumoral activity which is considered to be mainly due to the cytotoxic properties of mistletoe lectins, the main effective constituents of mistletoe extracts.

Administration, Intravesical↗
PubMed2003

Mistletoe in cancer - a systematic review on controlled clinical trials.

BACKGROUND: Mistletoe preparations are among the most widely used unconventional cancer therapies in Central Europe. Their clinical effectiveness, however, is controversial. OBJECTIVE: To investigate whether prospective controlled clinical trials provide evidence for efficacy of mistletoe therapy in cancer. DESIGN: Systematic review. MATERIAL AND METHODS: Search of 11 electronic databases, reference lists and expert consultations. Criteria based analysis was performed to assess methodological quality of the studies. RESULTS: Twenty-three studies were identified: 16 randomized, 2 quasi-randomized and 5 non-randomized. Cancer sites included breast, lung, stomach, colon, rectum, head and neck, kidney, bladder, melanoma, glioma, and genital. Among these studies, statistically significant positive outcomes were reported for survival (n = 8), tumor remission (n = 1), overall quality of life (QOL) (n = 3), and QOL in relation to side effects during cytoreductive therapy (n = 3). Further, positive trends were reported for survival (n = 8), disease-free-survival (n = 1), and tumor remission (n = 2). Several studies reported no effect on survival (n = 4), disease-free-survival (n = 1), recurrence (n = 2), remission (n = 3), and QOL (n = 1). One study showed a negative trend for disease-free-survival. However, methodological quality of the studies was sometimes far below the standard that is today regarded as optimal or necessary. In view of substantial heterogeneity of the studies and potential positive and negative biases, we considered effect size estimation by quantitative synthesis to be unreliable and decided on a non-quantitative synthesis and discussion. Mistletoe therapy was well tolerated, and no major side effects were noted. CONCLUSIONS: Among 23 identified studies evaluated for clinically relevant outcome measures, 12 studies showed one or more statistically significant, positive results, another 7 studies showed at least one positive trend, 3 showed no effect and 1 had a negative trend. All studies, however, suffered from methodological shortcomings to some degree, and many of the studies are not conclusive. As several reasonably well conducted studies indicate beneficial effects, further properly designed trials should be encouraged. Future controlled studies should take into account the methodological limitations and potential biases of these past mistletoe trials.

Antineoplastic Agents↗
PubMed1993

[The effect of mistletoe lectins on the limulus amebocyte lysate test].

Former reports about too high and from batch to batch changing endotoxin contents in mistletoe preparations and phytopharmaceuticals for parenteral administration correlated with clinically observed side effects led to investigations of the endotoxin content of ABNOBA-viscum. For that purpose the endotoxin levels of the raw materials, the equipment and the production steps were observed by using the limulus amebocyte lysate (LAL) test. The mean value found in the preparation containing the highest available concentration (dilution level 2 containing 15 mg of plant extract from 20 mg of fresh mistletoe in 1 ml) came to 66.7 endotoxin units (EU) per ml, corresponding to about one fifth of the commonly accepted limit value of 350 EU/ml, the human pyrogenic dose. Depending on their dilution level, lower concentrated preparations led also to lower LAL test results. It could be proved that lectins contained in mistletoe preparations cause false positive LAL tests. Such results implicate false too high contents of endotoxin. Different lysates, i.e. Limusate, Pyrogel, Pyrogent, and Pyroquant showed approximately the same results. Microbiological and LAL test results indicate that only 10% of the total amount of the LAL test result was caused by endotoxins. So it is necessary to form a new estimation of the former results of determination of the endotoxin content of mistletoe preparations.

Animals↗