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PubMed2000

[Oncologic mistletoe therapy: physicians' use and estimation of efficiency].

BACKGROUND AND OBJECTIVES: In the field of unorthodox therapies in oncology, mistletoe extracts represent the most important method in Germany. In spite of its use for decades, there is no sufficient evidence for its efficiency. Since physicians have been identified to be the main providers of unconventional cancer therapies, the question of what experiences they have made using mistletoe extracts and other methods. PERSONS AND METHODS: In a cross-sectional study, 202 physicians in their private practices answered a structured, pretested questionnaire on unconventional cancer therapies, including their attitudes towards them and their judgement on efficiency. Response rate 80.2%. RESULTS: 79.2% of the physicians reported to provide unconventional cancer therapies, especially older and more experienced doctors. Among these, the rate of physician with a special preference of mistletoe extracts was 44.4%. The average probability to achieve complete or partial remissions with mistletoe extracts, eventually in combination with other unconventional methods was estimated to be 6% and 15%, thus receiving slightly lower estimates than other methods. With respect to changes in quality of life, use of mistletoe extracts was judged to be inferior to other methods (pT-Test = 0.063; pT-Test = 0.059). Furthermore, mistletoe extracts were significantly less frequently used because the physician was convinced of its efficiency (p = 0.025). CONCLUSION: Clinical studies to prove possible benefits of mistletoe extracts are mandatory. It remains unclear why this method has become so popular in spite of providers moderate judgments on efficiency.

Adult↗
PubMed1997

Stimulation of the specific immune system by mistletoe extracts.

We have investigated the in vitro responsiveness of T cells from mistletoe-treated cancer patients and untreated donors to various preparations of mistletoe extracts. Proliferation of peripheral blood mononuclear cells from treated but not from untreated patients was observed in response to therapeutically used mistletoe extracts prepared from apple (mali) or pine (pini) host trees. The strongest proliferation was induced by vesicle preparation of mali extract. Using a newly developed flow cytometry assay (standard cell dilution assay), we determined that cell growth was restricted to CD4+ T cells. Analysis with a panel of monoclonal antibodies against variable regions of the T cell receptor beta chain (V beta) revealed an oligoclonal pattern of CD4+ T cell activation. These results indicate that therapeutic administration of mistletoe extracts sensitized a restricted set of CD4+ T lymphocytes in mistletoe-treated patients. Lymphocytes from untreated donors are only stimulated with heat-treated mistletoe extracts. The responding T cells are gamma delta T cells and express variable T cell receptor elements V gamma 9 and V delta 2. The gamma delta-stimulating activity of heat-treated mistletoe extracts is sensitive to treatment with alkaline phosphatase but not with proteinase K, indicating that the ligands are non-proteinaceous phosphate-containing compounds.

Adjuvants, Immunologic↗
PubMed2001

[Metaphorical aspects of mistletoe therapy in patients' experiences--a qualitative study].

OBJECTIVE: Mistletoe therapy is an item of research because of its immunological features. Nevertheless, mistletoe should be also an item of research because of its semiotics. Long before R. Steiner proposed mistletoe as an anticancer drug, this plant seemed to have its meaning not by pharmacodynamics but by pharmacosemiotics and magic. Thus, metaphorical aspects of mistletoe therapy should be described by processing the transcript and paintings from a therapeutic group session of cancer patients. Especially the relation between individually and historically coded metaphors should be looked at. MATERIAL AND METHODS: Sample of this qualitative study is the transcript of a therapeutic session of 12 female malignoma patients getting mistletoe infusions (Isorel(r)) since 1.5 years in a general practitioners' practice. Sequential coding of the transcript, inventory of themes, and structural hypothesis are the first steps. The structural hypothesis is triangulated by a textual corpus containing anthroposophic and ethnographic material; then a grounded theory is made. RESULTS: The material is divided. On the one hand, there is a huge amount of historically coded, stereotypic metaphors (sun, cancer, ritual). On the other hand, 'ritual' seems not only a stereotypic metaphor but also a container of individually coded metaphors concerning body experiences (proprioceptive etc.). Metaphors from anthroposophy are rare - the metaphors seem to stem from a deeper level of ethnographic sources. The whole session has a polyphone narrative structure. Categories of semiotics such as icon, index and symbol are only by the context of interaction a suitable description for mistletoe's metaphoric function. CONCLUSIONS: Problems of bias (denominator problem, valid but not reliable) are discussed, and a proposal is made for further forms of generalization of the results (semantic differentials). Moreover, it has to be asked if different preparations of mistletoe (e.g. lectine standard, draft from planta tota) make different halos of metaphors.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Treatment of advanced pancreatic cancer with mistletoe: results of a pilot trial.

Pancreatic cancer is a devastating disease with poor prognosis. It is characterized by its unresponsiveness to chemo- and/or radiotherapy. Therefore, many patients demand alternative drug therapy such as mistletoe treatment. However, there are no controlled data available analyzing the effect of mistletoe treatment in pancreatic cancer. In the present phase I/II study we evaluated the effect of mistletoe (Eurixor) treatment in 16 patients (7 women, 9 men) with histologically verified ductal pancreatic carcinoma. At the time when the patients were enrolled nine patients had lymph node metastases (stage III), and in 7 patients distant metastases (stage IV) were present. Mistletoe was administered twice a week by subcutaneous injection in a dosage of 1 ng per kg body weight. Monthly follow-ups included clinical status, multidimensional evaluation of quality of life, contrast enhanced computed axial tomography scan (CT scan) or ultrasonography, and determination of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Apart from one anaphylactic reaction, which necessitated suspension of treatment for a few days, no severe side effects were observed. No partial or complete remission was seen. Eight patients (50%) showed a CT-verified status of "no change" according to World Health Organization criteria for at least 8 weeks. Median survival time in all patients was 5.6 months (range 1.5 to 26.5 months). Analysis of multidimensional evaluation of quality of life showed a stable course of disease in 7 patients. All except two patients claimed that mistletoe had a positive effect on their quality of life, with an obvious decline only during the last weeks of life. These results indicate that mistletoe is not able to significantly influence tumor growth in advanced pancreatic carcinomas. However, mistletoe treatment can stabilize quality of life, and therefore may help patients to maintain adequate life quality in their few remaining months.

Aged↗
PubMed2006

Gene expression profiles of different breast cancer cells compared with their responsiveness to fermented mistletoe (Viscum album L.) extracts Iscador from oak (Quercus), pine (Pinus), white fir (Abies) and apple tree (Malus) in vitro.

Cytotoxicity assays in vitro (MTT test) showed that the different breast cancer cell lines Kpl-1, MCF-7 and Mfm-223 respond differently to the mistletoe (Viscum album L.) preparations Iscador. Quercus (Qu), Abies (A), Malus (M) and Pinus (P). In order to determine the differences in the responsiveness of the cells more exactly, the gene expression profiles were determined by cells, which were treated with Mistletoe extracts, compared with untreated control cells. Such differences can be analysed in more detail by looking at the gene expression using Human Whole Genome microarray chips (41,000 genes). The results of the transcriptome analyses suggested that Iscador preparations influenced the overregulation of genes regarding immune defense, stress response, apoptosis and cell-cell adhesion pathways. Within the Mfm-223-Zellen was the Genexpression in MCF-7 and Kpl-1. The MCF-7 cells were affected on the genes which are involved in cell-cell contacts whereas Kpl-1 responded to the mistletoe extracts by changing the mRNA levels of the immune and stress response pathways. Concerning the effects of the mistletoe extract, we conclude that Iscador Qu and M have a greater influence on the immune defense and stress response genes whereas Iscador A tends to affect the cell-cell adhesion and cytoskeleton pathways. In summary, cDNA microarray analyses give us information on whether a cancer cell is sensitive to mistletoe extracts in relation to how many genes are significantly overrepresented after mistletoe treatment, and whether a particular mistletoe extract is more effective on a specific cancer cell than the other preparation.

Abies↗
PubMed2005

Human cancer cells exhibit in vitro individual receptiveness towards different mistletoe extracts.

In vitro cytotoxic effects of three aqueous mistletoe extracts on cell physiology against different human tumor cell lines and primary cancer cells were investigated in order to compare the receptiveness of different cancer cells against different mistletoe products. Therefore cell proliferation (BrdU-incorporation assay), mitochondrial activity (MTT-testing) and necrotic cell toxicity (LDH assay) were assayed over serial dilutions of the test products. Data obtained with HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1 and VM-CUB1 tumor cell lines and Iscador M (20 mg/ml), Iscador Q (20 mg/ml) and Abnobaviscum Fraxini -2 (20 mg/ml) indicated significant growth-inhibition of all cell lines, but also different cell susceptibilities against the different extracts. These variations were not only monitored on established cell lines but also on primary mamma carcinoma cells from surgical resectates. Concerning cell proliferation and mitochondrial activity Abnobaviscum Fraxini exhibits stronger inhibitory effects compared to products from the Iscador series. In case the evaluation was standardized on the active contents of VAA-I within the different products, the Iscador extracts possess higher cytotoxic activity. Pure viscotoxins and mistletoe lectins exhibited less effects than the extracts. The simultaneous presence of pure mistletoe lectins and mistletoe polysaccharides diminished the VAA-mediated cytotoxic effects. The presence of fetal calf serum (FCS) in cultivation media during in vitro testing diminished the cytotoxic effects of mistletoe extracts. It was shown that in vivo application of mistletoe preparations led to the formation of antibodies against unknown compounds of the extracts, diminishing the cytotoxic effect.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts.

BACKGROUND: In single case observations, tumour remissions after intratumoral injections of mistletoe extracts have been described. MATERIALS AND METHODS: We investigated the antitumour activity of intratumorally (i.t.)-injected lectin-rich mistletoe extract at different dosages and i.t.-injected mistletoe lectin I in comparison to intravenous (i.v.) Gemcitabine and i.t. treatment with placebo in a human pancreatic cancer xenograft. RESULTS: In a preliminary dose-response experiment, the most marked tumour inhibition was induced when mistletoe extract was given at 8 mg/kg body weight (BW) and mistletoe lectin I at 5.3 microg/kg BW. In a second experiment, bi-weekly i.t. injections of mistletoe extract over 8 weeks resulted in a very high antitumour activity with an optimal T/C value (=median relative tumour volume of the test group vs. the control) of 0.4% combined with 3/8 partial and 3/8 complete remissions. Gemcitabine was less active with 2/8 partial and 1/8 complete remissions and an optimal TIC of 4.6%. CONCLUSION: I.t.-injected lectin-rich mistletoe extract should be further evaluated in patients with inoperable locally advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1996

Release of cytokines by a fermented lectin-1 (ML-1) free mistletoe extract reflects differences in the reactivity of PBMC in healthy and allergic individuals and tumour patients.

OBJECTIVE: Mistletoe extracts are used in adjuvant cancer treatment, but little is known concerning their mode of action. There is, however, evidence that antigens in these extracts may stimulate cells of the immune system, thereby modifying the altered immunological reactivity in tumour patients. METHODS: In order to find out whether the postulated immunomodulatory properties of mistletoe extracts are mediated by cytokines, a spectrum of different cytokines was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) from healthy (n = 23) and allergic (n = 16) individuals after stimulation with the fermented mistletoe lectin-1 (ML-1) free mistletoe extract Iscador Pini (IP) in vitro, and their cytokine patterns were compared to those from tumour patients with either breast cancer (n = 20) or colorectal tumours (n = 22). RESULTS: PBMC from healthy and allergic individuals produced high levels of TNF-alpha and IL-6 and to a lesser extent Th1- and Th2-related cytokines. This finding was in contrast to data obtained in tumour patients. Thus, the concentration of TNF-alpha was significantly lower in the cell cultures from breast cancer patients than in controls, and patients with colorectal tumours released IFN-gamma/IL-2 (5%) in the supernatants significantly less frequently than PBMC from healthy controls (26%). Similar results were obtained when the Th1- and monocyte/macrophage-related cytokines were analysed in the unstimulated cell cultures. CONCLUSIONS: These in vitro studies provide evidence that there is a reduced immunological reactivity to the fermented ML-1 free mistletoe extract in tumour patients and may give some clues as to how mistletoe-derived antigens could act on immune cells involved in the tumour defence.

Adult↗
PubMed1997

Effect of a mistletoe extract (Iscador QuFrF) on viability and migratory behavior of human peripheral CD4+ and CD8+ T lymphocytes in three-dimensional collagen lattices.

Migration and tissue distribution of immunocompetent cells may be critical prerequisites for efficient immune surveillance. The effect of various concentrations of the mistletoe extract Iscador QuFrF on the locomotory behavior and viability of immunomagnetically isolated human CD4+ and CD8+ T lymphocytes within three-dimensional collagen gels was investigated. Although variation in baseline activities of spontaneously migrating T cells was donor-dependent, a dose-dependent stimulation of the locomotory activity in both CD4+ and CD8+ T cells for noncytotoxic concentrations of Iscador QuFrF (0.25-1.25 micrograms/ml) was detected. The optimal concentration of mistletoe extract and time of maximal response were specific for each donor. As shown by cell tracking and subsequent data analysis, CD4+ T cells exposed to the mistletoe extract displayed a significant increase in mean velocity and time locomoting; total distance migrated was nearly doubled. In contrast, CD8+ T cells showed less pronounced changes in these critical parameters. Cytotoxic effects of the mistletoe preparation on T lymphocytes, which could at least partially be attributed to the induction of apoptosis, were drastically reduced in the presence of fetal calf serum in the culture system. Our data suggest that the direct stimulation of T-cell migration in the presence of mistletoe components may modulate in a dose-dependent manner the system of immune surveillance and recognition in patients under mistletoe therapy.

Adjuvants, Immunologic↗
PubMed2001

The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.

Adult↗
PubMed2003

Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation.

Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml(-1)). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.

Adenocarcinoma↗
PubMed2002

Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro.

Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins have been identified as the main active principle of mistletoe extracts. They have been shown to exhibit cytotoxic effects as well as immunomodulatory activities. The latter is exemplified by induction of cytokine secretion and increased activity of natural killer cells. Recent reports, however, indicated possible tumor growth stimulation by mistletoe extracts. Therefore, the three aqueous mistletoe extracts (Iscador M special, Iscador Qu special and Iscador P) were evaluated for antiproliferative and/or stimulatory effects in a panel of 16 human tumor cell lines in vitro using a cellular proliferation assay. The results show no evidence of stimulation of tumor growth by any of the three Iscador preparations, comprising central nervous system, gastric, non-small cell lung, mammary, prostate, renal and uterine cancer cell lines, as well as cell lines from hematological malignancies and melanomas. On the contrary, Iscador preparations containing a high lectin concentration (Iscador M special and Iscador Qu special) showed antitumor activity in the mammary cancer cell line MAXF 401NL at the 15 microg/ml dose level with a more than 70% growth inhibition compared to untreated control cells. In addition, a slight antitumor activity (growth inhibition 30-70%) was found in three tumor cell lines for Iscador M special and in seven tumor cell lines for Iscador Qu special, respectively. Iscador P, which contains no mistletoe lectin I, showed no antiproliferative activity.

Animals↗
PubMed1999

[Mistletoe therapy from the pharmacologic perspective].

Because of their cytostatic/apoptotic and immunomodulatory effects mistletoe extracts are often applied in tumour patients. Recent experimental data suggest that the mistletoe lectins Viscum album agglutinin (VAA)-I and -II are play an important role in the efficacy of mistletoe therapy. VAA-I and -II are members of the type-II ribosome-inactivating proteins. VAA-I has been shown to induce cytostatic effects in cultures of various eukaryotic cells in vitro. In 24-hour cultures of human peripheral lymphocytes, flow-cytometric investigations with propidium iodide (PI) in hypotonic buffer and quantitative assessment of DNA breaks with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay were carried out; they revealed a dose-dependent VAA-I-induced apoptosis (lectin concentrations between 10 ng/ml and 1 microg/ml). In 24-hour cultures of peripheral blood mononuclear cells (PBMC), VAA-I in non-cytotoxic concentrations (1+/-10 ng/ml) induced mRNA expression and enhanced the secretion of proinflammatory cytokines. The stimulation of NK cells by VAA-I in vitro was enhanced in additive manner by the combination of VAA-I with IL-2 and IL-12. In culture of PBMC and bone marrow CD34+ cells coincubation of VAA-I with other haematopoietic growth factors induced a dose-dependent increase in clonogenic growth. In cancer patients the mechanisms of natural immunity, believed to be essential for their survival, are often significantly decreased. VAA-I and standardized mistletoe extracts are able to stimulate the cellular parameters of natural immunity with a bell-shaped curve of efficacy. Studies in animal models suggest that application of 0.5-3 ng/kg VAA-I twice a week is effective in sustaining the elevation of the number and activity of peripheral blood NK cells. These parameters often exhibit high intrinsic fluctuations, in healthy persons, however, blind crossover studies reveal an optimal lectin dose of about 0.5 and 1 ng/kg bw, suggesting a potential use of mistletoe preparations as a modulator of the natural immune system. Selective apoptotic effects of VAA-I may represent a novel approach for pharmacological manipulation of the balance between cell growth and programmed cell death. Appropriate combination of immunomodulatory and cytotoxic doses may open new clinical perspectives in the mistletoe therapy.

Bone Marrow Cells↗
PubMed2000

Activation of c-Jun N-terminal kinase 1 (JNK1) in mistletoe lectin II-induced apoptosis of human myeloleukemic U937 cells.

Extracts of mistletoe (Viscum album var. coloratum) have been used for several decades as an anticancer immunomodulating agent in clinical fields. However, the mechanism by which the plant extracts kill tumor cells has remained elusive. We investigated the direct effects of beta-galactoside- and N-acetyl-d-galactosamine-specific mistletoe lectin II in inducing apoptotic death of U937 cells. Three distinct components of mistletoe, including beta-galactoside- and N-acetyl-D-galactosamine-specific lectin II (60 kDa), polysaccharides, and viscotoxin (5 kDa), induced apoptotic cell death, characterized by DNA ladder pattern fragmentation of U937 cells at 12 hr after treatment. Consistent with apoptosis of the cells, mistletoe extracts markedly increased the phosphotransferase activity of c-Jun N-terminal kinase 1 (JNK1)/stress-activated protein kinase (SAPK) in U937 cells. Among the three components, lectin II was the most potent in inducing apoptosis as well as JNK1 activation of U937 cells in a dose- and time-dependent manner. Catalytic activation of JNK1 induced by mistletoe lectin II was inhibited by the addition of peptide aC-DEVD-CHO, but not by aC-YVAD-CHO. In addition, mistletoe lectin II induced apoptosis in a variety of cell types including Jurkat T cells, RAW 264.7 cells, HL-60 cells, DLD-1 cells, and primary acute myelocytic leukemic cells.

Apoptosis↗
PubMedDate not supplied

Comparative analysis of phenolic acids in mistletoe plants from various hosts.

Phenolic acids present in mistletoe plants collected from various hosts were analysed with the use of HPLC. The following numbers of compounds were found in the mistletoe plant material gathered from respective hosts: Sorbus aucuparia- 12 compounds; Acer plantanoides--14 compounds: Malus domestica, Pyrus communis and Populus nigra--13 compounds each; Quercus robur--15 compounds. Altogether 21 phenolic acids were chromatographically identified in the tested material. The compounds were either free or combined as esters or glycosides. Comparative chromatography revealed qualitative differences in the investigated compounds between the various plant materials. For example o-coumaric acid was only found in mistletoe hosted by Quercus robur. Digallic acid was only found in the plant material hosted by Acer plantanoides. Qualitative and quantitative composition of mistletoes hosted by Malus domestica and Pyrus communis showed considerable similarities as far as phenolic acids were concerned. Moreover. vanillic acid. absent in all other batches of plant material, seemed to be characteristic of the above mistletoes. Quantitative HPLC analysis demonstrated a considerable content of salicylic acid (39.55 mg%) in mistletoe hosted by Sorbus aucuparia. Apart from the above material, this compound was only present in small quantities in plants hosted by Populus nigra (15.63 mg%) and Quercus robur (2.63 mg%).

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Patients are talking about ... Iscador (mistletoe).

Mistletoe generally is categorized as American mistletoe or European mistletoe. Despite its well-known potential for toxicity, mistletoe continues to be used as an herbal remedy and recently has received a great deal of media attention. The U.S. Food and Drug Administration classified mistletoe as a food additive that cannot be marketed unless proven safe for consumption (DerMarderosian, 1992). Several components of the plant have been found to possess antineoplastic activity and warrant further investigation for their clinical potential. At this time, however, mistletoe as a single-agent therapy has not been scientifically validated in the treatment of breast cancer.

Antineoplastic Agents↗
PubMed2006

Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis.

OBJECTIVE: Expanded presentation and re-analysis of previously published data of randomized and non-randomized studies on mistletoe therapy with breast cancer patients [3, 4]. The main question is: Does a re-analysis confirm the previously reported effects of prolonging the survival of patients with breast cancer under long-term application of a complementary/anthroposophic therapy with the European mistletoe preparation Iscador? DATA SOURCES: (1) Randomised matched-pairs study: Breast cancer patients with only lymphatic metastases (17 pairs) that had never used mistletoe therapy were matched for several prognostic factors. By paired random allocation, one patient of a pair received a suggestion of mistletoe therapy to be applied by the attending physician. (2) Non-randomised matched-pairs studies: Patients that had already received mistletoe (Iscador) therapy were matched to control patients from the same pool using the same prognostic criteria. Three groups were recruited by this procedure: breast cancer with local recurrences and no metastases (42 pairs), breast cancer with only lymphatic metastases (55 pairs), and breast cancer with distant metastases (83 pairs). ANALYSIS: Cox proportional hazard models and sensitivity analyses based on subsets of the original data sets according to strict or lose application of the matching criteria. RESULTS: The results of this re-analysis are consistent with the earlier results, even when comparing different methods and subsets. In the randomised study, the effect of long-term Iscador therapy on overall survival is significantly in favour of the Iscador therapy: Estimate of the median difference and 95 % confidence interval in years 2.5 (0.83, 4.50). The results for the non-randomised studies were also in favour of the Iscador therapy: Breast cancer with local recurrences and no metastases: estimate of hazard ratio and 95 % confidence interval 0.52 (0.23, 1.17); breast cancer with lymphatic metastases: 0.27 (0.15, 0.50); breast cancer with distant metastases: 0.53 (0.32, 0.88). As a short-term effect of this therapy, psychosomatic self-regulation noticeably increases within 3 months in the Iscador group in comparison to the control group in the randomised study: estimate of the median difference 0.90 (0, 1.75). CONCLUSION: The re-analysis demonstrates that the effects shown in the previously published data are consistent despite using different analytic methods and different subsets. Overall, the survival of patients receiving mistletoe treatment with Iscador is longer in these studies. In the short term, psychosomatic self-regulation, as a measure of autonomous coping with the disease, rises more under Iscador therapy than under conventional therapy alone.

Adult↗
PubMed2005

Complete structure determination of N-acetyl-D-galactosamine-binding mistletoe lectin-3 from Viscum album L. album.

The primary structure of the B chain of the N-acetyl-D-galactosamine-recognizing mistletoe lectin-3 (ML-3B) has been deduced from proteolytic digest peptides of the purified glycoprotein, their HPLC-separation and Edman degradation and confirmation of the peptide sequences by MALDI-MS. ML-3B consists of 262 amino acid residues including 10 cysteine moieties. The structure and linkage of the carbohydrate side chains, connected to two N-glycosylation sites at positions Asn(95) and Asn(135) of the lectin, were determined by a combination of glycosidase treatment and MALDI-MS of corresponding glycopeptide fragments. The sequence alignment reveals a high homology with other B chains of type-II RIPs, although there are remarkable differences in the D-galactose-specific mistletoe lectin-1B chain. The recently published primary structure of the mistletoe lectin-3A chain1 and the now available primary sequence of the 3B chain allowed the construction of a preliminary homology model of ML-3. The model demonstrates, unequivocally, that ML-3 is a member of the type-II RIP family with rigid conservation of the enzymatic active site of the A chain and an identical overall protein fold. Specific amino acid residue exchanges and the different glycosylation pattern in comparison with ML-1 are discussed and related to the properties of the two glycoproteins. The knowledge of the complete primary structure of mistletoe lectin-3 is a major contribution towards more insight into the mechanism of the biological activity of commercial mistletoe preparations.

Acetylgalactosamine↗