Cancer and Mistletoe Treatment

Cancer and Mistletoe Treatment

 

Mistletoe extracts (Viscum album L.) are widely used integrative cancer care treatments, particularly in Europe (1-5). They are an old herbal remedy (6, 7) and were introduced as a cancer treatment in 1920 by Rudolf Steiner and Ita Wegman, founders of Anthroposophic Medicine (8). Viscum album is a hemiparasitic shrub, growing on different host trees. Different preparations are available for the treatment of cancer (currently Abnobaviscum®, Helixor®, Iscador®, Iscucin®, and Lektinol®). They are available from different host trees such as oak, apple, pine, and many others. They are applied parenteral, particularly subcutaneous, but also intravenous, intratumoral, intrapleural, intraperitoneal, and other sites.

Several pharmacologically active compounds have been isolated from VAE, such as mistletoe lectins (ML I, II, and III) (9), viscotoxins (10, 11), oligo- and polysaccharides (12, 13), lipophilic extracts (14), and various others (6, 7). Currently, VAE triterpenes are gaining great interest. (15-19) The most prominent properties of VAE are their cytotoxic and growth-inhibiting effects, in vitro, on a variety of human tumor cell lines, lymphocytes, and fibroblasts (6, 7). The cytotoxic effects of VAE are mainly due to the apoptosis-inducing mistletoe lectins (20-22), while the viscotoxins induce necrotic cell death (21, 23). VAE is also recognized for their immune-modulating activity: In vitro and in vivo studies have demonstrated activation of monocytes/macrophages, granulocytes, natural killer (NK) cells, NK-cell mediated tumor cell lysis, T-cells (especially T-helper-cells), and the induction of various cytokines (6, 7, 24). VAE also downregulates tumor genes, reduces motility and invasiveness of tumor cells [24), and shows antiangiogenetic effects [25). They also possess DNA stabilizing properties, they reduce chromosome damage and improve DNA repair (26-29]. In animals, VAE displays potent antitumor effects when administered either directly into the tumor or systemically (6, 7, 30).

The clinical effectiveness of mistletoe extracts in cancer has been investigated in a great number of studies, among these 43 prospective randomized controlled trials (31-80): They predominantly report significant clinical benefits. With regard to the quality of studies and consistency of results, the best evidence concerning the efficacy of mistletoe therapy exists for the improvement of quality of life, an increase of weight, and improved tolerability of cytoreductive therapies (chemotherapy, radiotherapy, surgery) (33, 81, 82). Regarding survival, a well-designed randomized controlled trial has recently shown a highly significant benefit in advanced pancreatic cancer (32). Other studies showed similar results (30, 83-85). Effectiveness seems to depend on the duration of the mistletoe therapy, in addition to factors relating to dosage, host tree, and choice of preparation. Tumor remissions have been repeatedly observed after the local application of mistletoe extracts. This finding is consistent with the preclinical research on cytotoxicity and treatment of tumors in animals. During customary low-dose mistletoe therapy, tumor remissions are rare exceptions. Tumor remissions have therefore been reported primarily in small studies, case series, and single cases. (e.g. (30, 84, 86-96))

According to highly experienced practitioners, many improved outcomes are possible, with highly individualized and comprehensive treatment schedules – individually adjusted and with selected dosage, preparation, host tree, injection site, time schedule of administration, and supplementation with other interventions. This still needs to be investigated. (97, 98)

Currently, several interesting trials have been started: One large publicly funded confirmative (phase III) randomized controlled trial investigating the influence of mistletoe treatment on survival and health-related quality of life in patients with advanced pancreatic cancer, conducted at several cancer centers in Sweden (NCT02948309). One phase I trial on the safety of intravenous mistletoe infusions in various cancers, conducted at the John Hopkins Hospital in Baltimore (NCT03051477 [99)), funded by the charity organization Believe Big (www.believebig.org). And one large confirmative (phase III) randomized controlled on the efficacy and safety of intravesical mistletoe extract compared to Mitomycin installation in superficial bladder cancer, conducted in more than 30 German study sites. (100)

Clinical application of mistletoe extracts is safe, even in high dosages (6, 7, 101-106).

IFAEMM Freiburg at the Witten Herdecke University and the Center for Translational Medicine, Medical Center, University of Freiburg

Both Korean and European Mistletoe Lectin Enhances Natural Killer Cell Cytotoxicity via Upregulation of Perforin Expression

Abstract

Background: Natural killer (NK) cells are crucial components of the innate immune system, providing the first line of defense against pathogens and malignant cells. In a previous study, we demonstrated the prophylactic activity of water extract of Korean mistletoe (Viscum album coloratum) on tumor metastasis. However, the leading compound from the water extract of Korean mistletoe was not clearly addressed.

Objective: The purpose of this research was mainly focused on addressing the effect of Korean mistletoe lectin (KMLC) on NK cell cytotoxicity, and the ability of cytokine secretion as well as its signal transduction, mitogen-activated protein kinase (MAPK) pathway.

Methods: KMLC was used to test NK cell-mediated cytotoxicity in vitro and in vivo. Non-isotope cytotoxicity assay (bis-N, N, N’, N’-tetraacetic acid (BATDA) release assay) was performed to test the cytotoxicity of NK cells against target tumor cells. Receptor expression was checked by flow cytometry analysis and MAPK signal molecules were analyzed by immunoblotting.

Results and conclusions: KMLC at 200 ng/mL increased the cytotoxicity of NK92 cells by 35% compared with untreated cells. KMLC-treated (at 100 ng/mL) mice splenocytes showed a 20% increase in cytotoxic activity. Also, the B chain, one of the subchains of KMLC, increases perforin expression. We demonstrated that the signal transduction controlling NK cell cytotoxicity was mediated by upregulation of the NKG2D receptor and the expression of a cytotoxic effector molecule. These results strongly suggest that KMLC possesses immunological activity, mediated by NK cell activation.

Younghoon Kim, Inbo Kim, Choon-Ho Park, Jong Bae Kim in Asian Pac J Allergy Immunol: 2018 Sep;36(3):175-183.  DOI: 10.12932 / AP-030417-0067.

Antitumor Activity of the Korean Mistletoe Lectin is Attributed to Activation of Macrophages and NK Cells

Abstract

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum and album) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26-M3.1 carcinoma, and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same as that of 100 microg/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26-M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an essay for natural killer (NK) cell activity, i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

Taek Joon Yoon, Yung Choon Yoo, Tae Bong Kang, Seong Kyu Song, Kyung Bok Lee, Erk Her, Kyung Sik Song, Jong Bae Kim in: Arch Pharm Res. 2003 Oct;26(10):861-7.  doi: 10.1007/BF02980033.

Immunomodulatory Effects of Viscum Album Extracts on Natural Killer Cells: Review of Clinical Trials

Abstract

Extracts produced from Viscum album L. (mistletoe) are widely used in complementary and in standard medicine in Central and Northern Europe for the treatment of cancer. In many preclinical and clinical studies, Viscum album extracts were shown to exert significant immunomodulatory functions. Natural killer (NK) cells play an important role in cell-mediated immune responses against tumor cells. This article reviews clinical trials that address the influence of the mistletoe extract Iscador® on NK cells and discusses the results with regard to the NK cell functions assayed, to putative underlying mechanisms, and to the role of different mistletoe components.

Conclusion: Many preclinical and clinical trials demonstrated a positive effect of Iscador® treatment on NK cell function. Mistletoe lectins have an obvious immunomodulating effect and improve specifically TH-1 response and NK cell function and explain the positive findings in clinical trials in cancer patients and people living with HIV infection..

Sibylla Braedel-Ruoff; Review Forsch Komplementmed: in 2010 Apr;17(2):63-73. doi: 10.1159 / 000288702. Epub 2010 Mar 12.

Immunostimulatory Properties of Mistletoe Extracts and Their Application in Oncology

Abstract

For a long time cancer immunotherapy was overshadowed by chemotherapy and radiotherapy. Recently, “Science”, one of the world’s top scientific journals, named the stimulation of the body’s own immune system to fight cancer cells as the “breakthrough of the year”. In Germany, Switzerland, and Austria, extracts derived from mistletoe (Viscum album L.) such as Iscador, Abnobaviscum, Helixor, Iscar, Iscucin, and Israel have been used in oncology for many years. These extracts have immunomodulating and immunostimulating properties, as demonstrated by experimental studies as well as in clinical trials. The aim of our paper is to present immunological disorders associated with cancer, which can be counteracted by treatment with extracts derived from mistletoe. Although these drugs cannot replace conventional cancer treatment, they clearly improve patient’s quality and length of life.

Sylwia Wrotek, Robert Skawiński, Wiesław Kozak; Postepy Hig Med Dosw: 2014 Oct 23;68:1216-24. doi: 10.5604/17322693.1126850.

 

Immunomodulatory Effects of Viscum Album Extracts on Natural Killer Cells: Review of Clinical Trials

Abstract:

In Europe, extracts produced from Viscum album L. (mistletoe) are widely used in complementary and standard medicine for the treatment of cancer. In many preclinical and clinical studies, Viscum album extracts were shown to exert immunomodulatory functions. Natural killer (NK) cells play an important role in cell-mediated immune responses against tumor cells. This article reviews clinical trials that address the influence of the mistletoe extract Iscador® but also ABNOBA Viscum® on NK cells and discusses the results with regard to the NK cell functions assayed, to putative underlying mechanisms, and to the role of different mistletoe components.

Conclusion: Many clinical trials in various malignancies demonstrated a positive clinical effect of Mistletoe lectins treatment on NK cell function with resulting improvement of quality of life and life expectancy which can be explained by the improvement of NK cell activity. Sibylla Braedel-Ruoff in: Review Forsch Komplementmed. 2010 Apr;17(2):63-73. DOI: 10.1159 / 000288702. Epub 2010 Mar 12.

 

Adjuvant Therapy Using Mistletoe Containing Drugs Boosts the T-cell-mediated Killing of Glioma Cells and Prolongs the Survival of Glioma Bearing Mice

Abstract

Viscum album L. extracts (VE) are applied as complementary cancer therapeutics for more than one century. Extracts contain several compounds like mistletoe lectins (ML) 1-3 and viscotoxins, but also several minor ingredients. Since ML-1 has been described as one of the main active components harboring antitumor activity, purified native or recombinant ML-1 has been also used in clinical trials in the last years. The present study examined and compared the immune boosting effects of three ML-1 containing drugs (the extract ISCADOR Qu, the recombinant ML-1 Aviscumine, and purified native ML-1) in the context of the T-cell mediated killing of glioma cells. Additionally, we examined the possible underlying T-cell stimulating mechanisms. Using cocultures of immune and glioma cells, a PCR-based microarray, quantitative RT-PCR, and an antibody-based array to measure cytokines in blood serum, immune supporting effects were determined. A highly aggressive, orthotopic, immunocompetent syngeneic mouse glioma model was used to determine the survival of mice treated with ISCADOR Qu alone or in combination with tumor irradiation and temozolomide (TMZ). Treatment of glioblastoma (GBM) cells with ISCADOR Qu that contains a high ML concentration, but also viscotoxins and other compounds, as well as with Aviscumine or native ML-1, enhanced the expansion of cancer cell-specific T-cells as well as T-cell-mediated tumor cell lysis, but to a different degree. In GBM cells all three ML-1-containing preparations modulated the expression of immune response associated genes. In vivo, subcutaneous ISCADOR Qu injections at increasing concentration induced cytokine release in immunocompetent VM/Dk-mice. Finally, ISCADOR Qu, if applied in combination with tumor irradiation and TMZ, further prolonged the survival of glioma mice. Our findings indicate that ML-1 containing drugs enhance anti-GBM immune responses and work in synergy with radiochemotherapy. Therefore, adjuvant mistletoe therapy should be considered as an auspicious treatment option for glioma patients.

Sonja Schötterl , Stephan M Huber, Hans Lentzen, Michel Mittelbronn, Ulrike Naumann in: Evid Based Complement Alternat Med, 2018 Aug 27;2018:3928572.  doi: 10.1155/2018/3928572. eCollection 2018.

 

Immune Modulation Using Mistletoe (Viscum Album L.) Extracts Iscador

Abstract

One repeatedly finds that mistletoe (Viscum album L.) extracts show immune-modulating effects. This is also true in many cases in the experimental setting. Many of the experimental trials cannot, however, be transferred to the clinical situation – or only in a limited way. The aim of this work was to pursue the question of the extent to which the function of immune-competent cells can be influenced by mistletoe extracts. To do this, 3 clinical studies were carried out. Results from the first two studies will be presented here. In a prospective observational study with defined inclusion and exclusion criteria, the impact of two different doses of Iscador M (Mali) or Iscador Qu (Quercus) on the function and number of T-lymphocytes from tumor patients was studied. The immunological tests took place monthly during the first six months. Thirty-one patients were included in the slow dose group and 36 patients in the group with swift dose escalation. It was postulated that a too swift increase in dosage would lead to stronger local reactions and impairment of the stimulation capacity of T-cells taken ex vivo and incubated for 72 h. The evaluation showed that patients with stronger local reactions at the injection site have an impairment of mitogen-induced stimulation capacity of T-cells. However, patients with stronger local reactions showed a significant decrease of HLA-DR+ T cells as compared to patients In a GCP-conform, controlled bicentric phase II study the aim was to investigate the efficacy of a perioperative intravenous mistletoe extract application on the modulation of operation-induced immune suppression. For this purpose, 105 patients with breast cancer were recruited. At the treatment center, the patients received an infusion of 1 mg Iscador M Spezial prior to the start of an operation, in addition to normal medication, while this was not practiced at the control center. The primary trial objective was the oxidative burst in granulocytes taken from patients ex vivo prior to surgery, and 1 and 3 days after. In order to take account of possible differences in the two groups, propensity scores were used as the basis for a matched pair analysis. It became clear that inhibition of the granulocyte function in the treatment group was significantly less marked (p < 0.001; Wilcoxon). Mistletoe extract-related adverse reactions were not observed. Thus this special form of application could minimize the immune suppression triggered by general anesthesia and operation stress.

Arndt Büssing: Arzneimittelforschung: 2006 Jun;56(6A):508-15. doi: 10.1055 / s-0031-1296818.

 

Complementary Treatment With Mistletoe Extracts During Chemotherapy: Safety, Neutropenia, Fever, and Quality of Life Assessed in a Randomized Study

Abstract

Objectives: Evaluate the safety and clinical response of complementary treatment with European mistletoe extracts during chemotherapy.

Design: Monocentric controlled trial with 195 patients randomized into three groups.

Settings/location: National Cancer Research Center of Serbia.

Subjects: Breast cancer patients (stage T1-3N0-2M0) undergoing surgery and adjuvant chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluorouracil.

Interventions: Two different European mistletoe extracts (Helixor A, Iscador M Spez) were injected three times per week during 18 weeks of chemotherapy in the mistletoe group. A five-year follow-up of routine visits was documented in case report forms.

Outcome measures: Safety was assessed by measuring adverse events, body temperature during chemotherapy, and probability of relapse or metastasis in a 5-year follow-up. During chemotherapy, the neutrophil count and quality of life according to EORTC QLQ-C30 were assessed.

Results: The two patient groups receiving different mistletoe treatments were integrated into one mistletoe group for this safety analysis. Patients in the mistletoe group did not develop more fever symptoms than patients in the control group (two short-term events in each group). No significant differences in the probability of relapse or metastasis were measured between the groups (p = 0.7637). The mistletoe group showed a trend toward less neutropenia (p = 0.178) and improved pain and appetite loss scores (p < 0.0001 and p = 0.047, respectively) while having positive, but not significant, impact on other EORTC QLQ-C30 scores.

Conclusions: Mistletoe extracts were safe in this clinical study. Neither did subcutaneous injections induce fever, nor did they influence the frequency of relapse and metastasis within 5 years. This result suggests that mistletoe extracts had no adverse interactions with the anticancer agents used in this study. Furthermore, several side effects of chemotherapy decreased significantly in breast cancer patients.

Florian Pelzer, Wilfried Tröger, Nat J Altern Complement Med: Sep/Oct 2018;24(9-10):954-961. doi: 10.1089/acm.2018.0159.

 

Plant-Derived Lectins as Potential Cancer Therapeutics and Diagnostic Tools

Abstract

Cancer remains a global health challenge, with high morbidity and mortality, despite the recent advances in diagnosis and treatment. Multiple compounds assessed as novel potential anticancer drugs derived from natural sources, including microorganisms, plants, and animals. Lectins, a group of highly diverse proteins of nonimmune origin with carbohydrate-binding abilities, have been detected in virtually all kingdoms of life. These proteins can interact with free and/or cell surface oligosaccharides and might differentially bind cancer cells since the malignant transformation is tightly associated with altered cell surface glycans. Therefore, lectins could represent a valuable tool for cancer diagnosis and be developed as anticancer therapeutics. Indeed, several plant lectins exert cytotoxic effects mainly by inducing apoptotic and autophagic pathways in malignant cells. This review summarizes the current knowledge regarding the basis for the use of lectins in cancer diagnosis and therapy, providing a few examples of plant-derived carbohydrate-binding proteins with demonstrated antitumor effects.

Milena Mazalovska, J Calvin KouokamBiomed Res Int; 2020 May 15;2020:1631394. doi: 10.1155 / 2020 / 1631394. eCollection 2020.

 

Could Plant Lectins Become Promising Anti-Tumour Drugs for Causing Autophagic Cell Death?

 

Abstract

Plant lectins, a group of highly diverse carbohydrate-binding proteins of non-immune origin, are ubiquitously distributed through a variety of plant species and have recently drawn rising attention due to their remarkable ability to kill tumor cells using mechanisms implicated in autophagy. In this review, we provide a brief outline of the structures of some representative plant lectins such as concanavalin A, Polygonatum cyrtonema lectin, and mistletoe lectins. These can target autophagy by modulating BNIP-3, ROS-p38-p53, Ras-Raf, and PI3KCI-Akt pathways, as well as Beclin-1, in many types of cancer cells. In addition, we further discuss how to plant lectins are able to kill cancer cells by modulating autophagic death, for therapeutic purposes. Together, these findings provide a comprehensive perspective concerning plant lectins as promising new anti-tumor drugs, with respect to autophagic cell death in future cancer therapeutics.

Z Liu, Y Luo, T-T Zhou, W-Z Zhang: Cell Prolif; 2013 Oct;46(5):509-15.  DOI: 10.1111/cpr.12054.  Epub 2013 Aug 24.

 

Immunomodulating properties of Aqueous Viscum album extracts in vivo and in vitro

Abstract

Mistletoe extracts have clear immunomodulatory activity. We show that nontoxic concentrations of Viscum album extracts increase natural killer (NK) cell-mediated killing of tumor cells but spare nontarget cells from NK lysis. The compounds responsible for this bioactivity were isolated from mistletoe and characterized. They have low molecular mass and are thermostable and protease-resistant. After complete purification by HPLC, they were identified by tandem MS as viscotoxins A1, A2, and A3 (VTA1, VTA2, and VTA3, respectively). Whereas micromolar concentrations of these viscotoxins are cytotoxic to the targets, the bioactivity with respect to NK lysis is within the nanomolar range and differs between viscotoxin isoforms: VTA1 (85 nm), VTA2 (18 nm), and VTA3 (8 nm). Microphysiometry and assays of cell killing indicate that, within such nontoxic concentrations, viscotoxins do not activate NK cells, but act on cell conjugates to increase the resulting lysis.

Tabasco J, Pont F, Fournie JJ, Vercellone French Institute of Health and Medical Research: European Journal of Biochemistry 269(10):2591-600 · June 2002; Source: PubMed.

References

(1) Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Brownell M, Magri M, Selvekerova S: Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol 2005, 16(4):655.

(2) Weis J, Bartsch HH, Hennies F, Rietschel M, Heim M, Adam G, G„rtner U, Ammon A: Complementary medicine in cancer patients: demand, patients’ attitudes, and psychological beliefs. Onkologie 1998, 21:144-149.

(3) Petru E, Schmied P, Petru C: Komplementäre Maßnahmen bei Patientinnen mit gynäkologischen Malignomen unter Chemo- und Hormontherapie – Bestandsaufnahme und kritische Überlegungen für die Praxis. Geburtshilfe Frauenheilkd 2001, 61:75-78.

(4) Längler A, Spix C, Seifert G, Gottschling S, Graf N, Kaatsch P: Complementary and alternative treatment methods in children with cancer: A population-based retrospective survey on the prevalence of use in Germany. Eur J Cancer 2008, 44(15):2233-2240.

(5) Fasching PA, Thiel F, Nicolaisen-Murmann K, Rauh C, Engel J, Lux MP, Beckmann MW, Bani MR: Association of complementary methods with quality of life and life satisfaction in patients with gynecologic and breast malignancies. Support Care Cancer 2007, 55(11):1277-1284.

(6) Kienle GS, Kiene H: Die Mistel in der Onkologie – Fakten und konzeptionelle Grundlagen. Stuttgart, New York: Schattauer Verlag; 2003.

(7) Büssing A: Mistletoe. The Genus Viscum Amsterdam: Hardwood Academic Publishers; 2000.

(8) Kienle GS, Kiene H, Albonico HU: Anthroposophic Medicine: Effectiveness, Utility, Costs, Safety. Stuttgart, New York: Schattauer Verlag; 2006.

(9) Franz H, Ziska P, Kindt A: Isolation and properties of three lectins from mistletoe (Viscum album L.). Biochemical Journal 1981, 195:481-484.

(10) Winterfeld K, Bijnen AB: Viscotoxin, ein neuer Inhaltsstoff der Mistel ( Viscum album L.). Liebigs Ann Chem 1948, 561:107-115.

(11) Winterfeld K, Kronenthaler A: Zur Chemie des blutdrucksenkenden Bestandteils der Mistel. (Viscum album). Arch Pharm 1942, 280:103-115.

(12) Mueller EA, Anderer FA: A Viscum album oligosaccharide activating human natural cytotoxicity is an interferon-gamma inducer. Cancer Immunol Immunother 1990, 32:221-227.

(13) Klett CY, Anderer FA: Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from Viscum album extract. Arzneimittel-Forschung/Drug Research 1989, 39 (II)(12):1580-1585.

(14) Urech K, Scher JM, Hostanska K, Becker H: Apoptosis-inducing activity of viscin, a lipophilic extract from Viscum album L. Journal of Pharmacy and Pharmacology 2005, 57 101-109.

(15) Strut CM, Jager S, Kersten A, Schempp CM, Scheffler A, Martin SF: Triterpenoids amplify anti-tumoral effects of mistletoe extracts on murine B16.f10 melanoma in vivo. PLoS One 2013, 8(4):e62168.

(16) Strut CM, Jager S, Schempp CM, Scheffler A, Martin SF: A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells. Phytother Res 2012, 26(10):1507-1512.

(17) Delebinski CI, Jaeger S, Kemnitz-Hassanin K, Henze G, Lode HN, Seifert GJ: A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukemia. Cell Prolif 2012, 45(2):176-187.

(18) Kleinsimon S, Kauczor G, Jaeger S, Eggert A, Seifert G, Delebinski C: ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs. BMC Complement Altern Med 2017, 17(1):26.

(19) Twardziok M, Kleinsimon S, Rolff J, Jager S, Eggert A, Seifert G, Delebinski CI: Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma. PLoS One 2016, 11(9):e0159749.

(20) Büssing A: Induction of apoptosis by the mistletoe lectins: a review on the mechanisms of cytotoxicity mediated by Viscum album L. Apoptosis 1996(1):25-32.

(21) Büssing A, Vervecken W, Wagner M, Wagner B, Pf ller U, Schietzel M: Expression of mitochondrial Apo2.7 molecules and Caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry 1999, 37(2):133-139.

(22) Janssen O, Scheffler A, Kabelitz D: In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneimittel-Forschung/Drug Research 1993, 43(II)(11):1221-1227.

(23) Büssing A, Schaller G, Pfüller U: Generation of reactive oxygen intermediates (ROI) by the thionins from Viscum album L . . Anticancer Res 1998, 18:4291-4296.

(24) Podlech O, Harter PN, Mittelbronn M, Poschel S, Naumann U: Fermented mistletoe extract as a multimodal antitumoral agent in gliomas. Evid Based Complement Alternat Med 2012, 2012:501796.

(25) Elluru SR, Van Huyen JPD, Delignat S, Prost F, Heudes D, Kazatchkine MD, Friboulet A, Kaveri SV: Antiangiogenic properties of Viscum album extracts are associated with endothelial cytotoxicity. Anticancer Res 2009, 29(8):2945.

(26) Büssing A, Azhari T, Ostendorp K, Lehnert A, Schweizer K: Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. Eur J Cancer 1994, 30A(12):1836-1841.

(27) Büssing A, Jungmann H, Suzart K, Schweizer K: Suppression of sister chromatid exchange-inducing DNA lesions in cultured peripheral blood mononuclear cells by Viscum album L. J Exp Clin Cancer Res 1996, 15:107-114.

(28) Büssing A, Regnery A, Schweizer K: Effects of Viscum album L. on cyclophosphamide-treated peripheral blood mononuclear cells in vitro: sister chromatid exchanges and activation/proliferation marker expression. Cancer Letters 1995(94):199-205.

(19) Kovacs E, Hajto T, Hostanska K: Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador). Eur J Cancer 1991, 27(12):1672-1676.

(30) Kienle GS, Glockmann A, Schink M, Kiene H: Viscum album L. extracts in breast and gynecologic cancers: A systematic review of clinical and preclinical research. J Exp Clin Cancer Res 2009, 28(79):doi:10.1186/1756-9966-1128-1179.

(31) Gaafar R, Rahman A, Aboulkasem F, El Bastawisy A: Mistletoe preparation (Viscum Fraxini-2) as palliative treatment for malignant pleural effusion: a feasibility study with comparison to bleomycin. ecancermedicalscience 2014, 8:424.

(32) Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomized clinical trial on overall survival. Eur J Cancer 2013, 49(18):3788-3797.

(33) Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Quality of life of patients with advanced pancreatic cancer during treatment with the mistletoe-a randomized controlled trial. Dtsch Arztebl Int 2014, 111(29-30):493-502.

(34) Bar-Sela G, Wollner M, Hammer L, Agbarya A, Dudnik E, Haim N: Mistletoe as a complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: A randomized phase II study. Eur J Cancer 2013, 49(5):1058-1064.

(35) Grah C: Misteltherapie bei nichtkleinzelligem Bronchialkarzinom. Randomisierte, offene Phase-II- Studie zur Untersuchung der Verträglichkeit und Wirksamkeit von Viscum-album-Extrakt in der palliativen, additiven Behandlung des fortgeschrittenen nichtkleinzelligen Bronchialkarzinoms. GKH Havelhöhe, Akademisches Lehrkrankenhaus der medizinischen Fakultät der Charité, Universitätsmedizin Berlin; 2010.

(36) Grah C, Matthes B, Happel H, Lemmens HP: Randomisierte, offene Phase-II-Studie zur Untersuchung von Viscum album-Extrakt in der palliativen, additiven Behandlung des fortgeschrittenen nichtkleinzelligen Bronchialkarzinoms (NSCLC). In: Die Mistel in der Tumortherapie 3 Aktueller Stand der Forschung und klinische Anwendung. edn. Edited by Scheer R, Alban S, Becker H, Blaschek W, Kreis W, Matthes H, Schilcher H, Stange R. Essen: KVC Verlag; 2013: 389-401.

(37) Longhi A, Reif M, Mariani E, Ferrari S: A Randomized Study on Postrelapse Disease-Free Survival with Adjuvant Mistletoe versus Oral Etoposide in Osteosarcoma Patients. Evid Based Complement Alternat Med 2014, 2014:210198.

(38) Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R: Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study. BMC Complement Altern Med 2012, 12(1):172.

(39) Grossarth-Maticek R, Ziegler R: Kontrollierte Studien zur präventiven Misteltherapie bei Myomen, Endometriosen und Cervix Dysplasie. In: Die Mistel in der Tumortherapie 2 – Aktueller Stand der Forschung und klinische Anwendung. edn. Edited by Scheer R, Alban S, Becker H, Holzgrabe U, Kemper FH, Kreis W, Matthes H, Schilcher F. Essen: KVC Verlag; 2009: 537-550.

(40) Hekal IA, Samer T, Ibrahim EI: Viscum Fraxini 2, as adjuvant therapy after resection of superficial bladder cancer: Prospective clinical randomized study. Abstract P8. In.; 2009: 120.

(41) Tröger W, Jezdic S, Zdrale Z, Tisma N, Hamre HJ, Matijasevic M: Quality of life and neutropenia in patients with early-stage breast cancer: A randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone. Breast Cancer: Basic and Clinical Research 2009, 3:35-45.

(42) Tröger W, Matijasevic M, Zdrale Z, Tisma N, Jezdic S: Additional therapy with mistletoe extracts in breast cancer patients receiving chemotherapy: a prospective randomized open label pilot study. In: Die Mistel in der Tumortherapie 2 – Aktueller Stand der Forschung und klinische Anwendung. edn. Edited by Scheer R, Alban S, Becker H, Holzgrabe U, Kemper FH, Kreis W, Matthes H, Schilcher H. Essen: KVC-Verlag; 2009: 509-521.

(43) Tröger W, Zdrale Z, Stankovic N, Matijass¡evic M: Five-Year Follow-Up of patients with early-stage Breast cancer After a Randomized study comparing Additional Treatment with Viscum Album (L.) extract to chemotherapy Alone. Breast Cancer: Basic and Clinical Research 2012, 6:173.

(44) Tröger W, Zdrale Z, Tisma N, Matijasevic M: Additional therapy with a mistletoe product during adjuvant chemotherapy of breast cancer patients improves the quality of life. Evidence-Based Complimentary and Alternative Medicine 2014, In press.

(45) Büssing A, Brückner U, Enter-Weis U, Schnelle M, Schumann A, Schietzel M, Hatzmann W, Hackmann J: Modulation of chemotherapy-associated immunosuppression by intravenous application of Viscum album L. extract (Iscador): a randomized phase II study. . Eur J Integr Med 2008, 1:S44-S45.

(46) Grossarth-Maticek R, Ziegler R: Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res 2008, 13 107-120.

(47) Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of ovarian cancer patients with mistletoe ( Viscum album L.) extracts Iscador. Arzneimittel-Forschung/Drug Research 2007, 57 (10):665-678.

(48) Grossarth-Maticek R, Ziegler R: Wirksamkeit und Unbedenklichkeit einer Langzeitbehandlung von Melanompatienten mit einem Mistelpräparat (Iscador© ) Schweizerische Zeitschrift für Ganzheitsmedizin 2007, 19 325-332.

(49) Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador©) Forsch Komplementarmed Klass Naturheilkd 2007, 14 140-147.

(50) Schink M, Tröger W, Davidian A, Goyert A, Scheuerecker H, Meyer J, Fischer IU, Glaser F: Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. A randomized phase III trial. Forsch Komplementarmed Klass Naturheilkd 2007, 14 (1):9-17.

(51) Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador). Forsch Komplementarmed Klass Naturheilkd 2006, 13 285-292.

(52) Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador) – Supplementary materials. In.; 2006.

(53) Auerbach L, Dostal V, Vclavik-Fleck I, Kubista E, Rosenberger A, Rieger S, Tr”ger W, Schierholz JM: Signifikant höherer Anteil aktivierter NK-Zellen durch additive Misteltherapie bei chemotherapierten Mamma-Ca-Patientinnen in einer prospektiven randomisierten doppelblinden Studie. In: Fortschritte in der Misteltherapie Aktueller Stand der Forschung und klinischen Anwendung. edn. Edited by Scheer R, Bauer R, Becker H, Fintelmann V, Kemper FH, Schilcher H. Essen: KVC Verlag; 2005: 543-554.

(54) Enesel MB, Acalovschi I, Grosu V, Sbarcea A, Rusu C, Dobre A, Weiss T, Zarkovic K: Perioperative application of the Viscum album extract Israel in digestive tract cancer patients. Anticancer Res 2005, 25 4583-4590.

(55) Eggermont A, Kleeberg UR, Ruiter DJ, Suciu S: European Organization for Research and Treatment of Cancer Melanoma Group trial experience with more than 2,000 patients, evaluating adjuvant treatment with low or intermediate doses of interferon alpha-2b. In: American Society of Clinical Oncology Educational Book. eds. Edited by American Society of Clinical O. Baltimore, MD: Lippincott Williams & Wilkins; 2001: 88-93.

(56) Kleeberg UR, Suciu S, Brücker EB, Ruiter DJ, Chartier C, Li‚nard D, Marsden J, Schadendorf D, Eggermont AMM: Final results of the EORTC 18871/DKG 80-1 randomized phase III trial: rIFN-à2b versus rIFN- g versus Iscador M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3mm) or regional lymph node metastasis. Eur J Cancer 2004, 40:390-402.

(57) Piao BK, Wang YX, Xie GR, Mansmann U, Matthes H, Beuth J, Lin HS: 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. Anticancer Res 2004, 24(1):303-309.

(58) Cazacu M, Oni T, Lungoci C, Mihailov A, Cipak A, Klinger R, Weiss T, Zarkovic N: The influence of Israel on the advanced colorectal cancer. Cancer Biotherapy & Radiopharmaceuticals 2003, 18(1):27-34.

(59) Borrelli E: Evaluation of the quality of life in breast cancer patients undergoing lectin standardized mistletoe therapy. Minerva Medica 2001, 92 (Suppl. 1):105-107.

(60) Grossarth-Maticek R, Kiene H, Baumgartner S, Ziegler R: 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. Alternative Therapies in Health and Medicine 2001, 7(3):57-78.

(61) Kim MH, Park YK, Lee SH, Kim SC, Lee SY, Kim CH, Kim YK, Kim KH, Moon HS, Song JS et al: Comparative study on the effects of a Viscum album (L.) extract (mistletoe) and doxycycline for pleurodesis in patients with malignant pleural effusion. 51st Meeting of The Korean Association of Internal Medicine. Translation by Helixor Heilmittel GmbH. Korean Journal of Medicine 1999, 57(Suppl. II): S121.

(62) Dold U, Edler L, Mäurer H C, Müller-Wening D, Sakellariou B, Trendelenburg F, Wagner G: Krebszusatztherapie beim fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom. Stuttgart, New York: Georg Thieme Verlag; 1991.

(63) Salzer G, Danmayr E, Wutzlhofer F, Frey S: Adjuvante Iscador-Behandlung operierter nicht kleinzelliger Bronchuskarzinome. Dtsch Z Onkol 1991, 23(4):93-98.

(64) Gutsch J, Berger H, Scholz G, Denck H: Prospektive Studie beim radikal operierten Mammakarzinom mit Polychemotherapie, Helixor und unbehandelter Kontrolle. Dtsch Z Onkol 1988(4):94-100.

(65) Salzer G: 30 Jahre Erfahrung mit der Misteltherapie an Öffentlichen Krankenanstalten. In: Misteltherapie Eine Antwort auf die Herausforderung Krebs. edn. Edited by Leroi R. Stuttgart: Verlag Freies Geistesleben; 1987: 173-215.

(66) Douwes FR, Wolfrum DI, Migeod F: Ergebnisse einer prospektiv randomisierten Studie: Chemotherapie versus Chemotherapie plus “Biological Response Modifier” bei metastasierendem kolorektalen Karzinom. Krebsgeschehen 1986, 18(6):155-163.

(67) Lange O, Scholz G, Gutsch J: Modulation der subjektiven und objektiven Toxizität einer aggressiven Chemotherapie mit Helixor. Unpublished Report. In.; 1985.

(68) Salzer G, Havelec L: Adjuvante Iscador-Behandlung nach operiertem Magenkarzinom. Ergebnisse einer randomisierten Studie. Krebsgeschehen 1983, 15(4):106-110.

(69) Salzer G: Prospektiv randomisierte Studie: Operiertes Magenkarzinom – Adjuvante Behandlung mit Iscador. Dtsch Z Onkol 1988, 20(4):90-93.

(70) Salzer G, Denck H: Randomisierte Studie über medikamentöse Rezidivprophylaxe mit 5-Fluorouracil und Iscador beim resezierten Magenkarzinom – Ergebnisse einer Zwischenauswertung. Krebsgeschehen 1979, 11(5):130-131.

(71) Steuer-Vogt MK, Bonkowski V, Ambrosch P, Scholz M, Neiá A, Strutz J, Hennig M, Lenartz T, Arnold W: The effect of an adjuvant mistletoe treatment program in resected head and neck cancer patients: a randomized controlled clinical trial. Eur J Cancer 2001, 37:23-31.

(72) Heiny BM: Additive Therapie mit standardisiertem Mistelextrakt reduziert die Leukopenie und verbessert die Lebensqualität von Patientinnen mit fortgeschrittenem Mammakarzinom unter palliativer Chemotherapie (VEC-Schema). Krebsmedizin 1991, 12(Sonderdruck):1-14.

(73) Heiny BM, Albrecht V: Komplementäre Therapie mit Mistellektin-1-normiertem Extrakt. Lebensqualitätsstabilisierung beim fortgeschrittenen kolorektalen Karzinom – Fakt oder Fiktion? Die Medizinische Welt 1997, 48:419-423.

(74) Lenartz D, Dott U, Menzel J, Schierholz JM, Beuth J: Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 2000, 20(3B):2073-2076.

(75) Lenartz D, Stoffel B, Menzel J, Beuth J: Immunoprotective activity of the galactoside-specific lectin from Mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 1996, 16:3799-3802.

(76) Brinkmann OA, Lümmen G, Luboldt HJ, Hertle L, Rübben H: Interferon à, interleukin 2 and 5-flourouracil compared with mistletoe lectin in metastatic renal cell carcinoma (MRCC). European Urology 2000, 37(Suppl. 2):152.

(77) Lümmen G, Brinkmann OA, Luboldt HJ, Hertle L, Rübben H: Interferon-a, interleukin-2 and 5-fluorouracil versus mistletoe lectin in metastatic renal cell carcinoma: Long-term results. European Urology 2001, 39(Spplement 5):121.

(78) Goebell PJ, Otto T, Suhr J, Rübben H: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. The Journal of Urology 2002, 168:72-75.

(79) Semiglasov VF, Stepula VV, Dudov A, Lehmacher W, Mengs U: The standardized mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomized, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 2004, 24:1293-1302.

(80) Semiglasov VF, Stepula VV, Dudov A, Schnitker J, Mengs U: Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomized, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 2006, 26 1519-1530.

(81) Kienle GS, Kiene H: Influence of Viscum Album L (European Mistletoe) Extracts on Quality of Life in Cancer Patients: A Systematic Review of Controlled Clinical Studies. Integr Cancer Ther 2010, 9(2):142-157.

(82) Horneber MA, Bueschel G, Huber R, Linde K, Rostock M: Mistletoe therapy in oncology. Cochrane Database Syst Rev 2008(2): CD003297.

(83) Kienle GS, Berrino F, Büssing A, Portalupi E, Rosenzweig S, Kiene H: Mistletoe in cancer – a systematic review on controlled clinical trials. Eur J Med Res 2003, 8:109-119.

(84) Kienle GS, Kiene H: Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res 2007, 12(3):103-119.

(85) Kienle GS, Glockmann A, Grugel R, Hamre HJ, Kiene H: Clinical research on anthroposophic medicine:update of a health technology assessment report and status quo. Forsch Komplementarmed Klass Naturheilkd 2011, 18(5):269-282.

(86) Embed M, El-Helw L, Sharma S: Phase II study of Viscum fraxini-2 in patients with advanced hepatocellular carcinoma. Br J Cancer 2004, 90:65-69.

(87) Mahfouz MM, Ghaleb HA, Zawawy A, Scheffler A: Significant tumor reduction, improvement of pain and quality of life, and normalization of sleeping patterns of cancer patients treated with a high dose of mistletoe. Ann Oncol 1998, 9(S2):129.

(88) Mahfouz MM, Ghaleb HA, Hamza MR, Fares L, Moussa L, Moustafa A, El-Za Way A, Kourashy L, Mobarak L, Saed S, et al: Multicenter open-labeled clinical study in advanced breast cancer patients. A preliminary report. Journal of the Egyptian NatCancer Inst 1999, 11 (3):221-227.

(89) Seifert G, Tautz C, Seeger K, Henze G, Laengler A: Therapeutic use of mistletoe for CD30+ cutaneous lymphoproliferative disorder / lymphomatoid papulosis. J Eur Acad Dermatol Venereol 2006, 21 1-2.

(90) Werthmann PG, Helling D, Heusser P, Kienle GS: Tumour response following high-dose intratumoral application of Viscum album on a patient with adenoid cystic carcinoma. BMJ Case Reports 2014:doi: 10.1136/bcr-2013-203180.

(91) Werthmann PG, Sträter G, Friesland H, Kienle GS: Durable Response of Cutaneous Squamous Cell Carcinoma Following High-dose Peri-lesional Injections of Viscum album Extracts – A Case Report. Phytomedicine 2013, 20:324-327.

(92) Orange M, Fonseca M, Lace A, von Laue HB, Geider S: Durable tumor responses following primary high-dose induction with mistletoe extracts: Two case reports. Eur J Integr Med 2010, 2:63-69.

(93) Orange M, Lace A, Fonseca M, von Laue HB, Geider S, Kienle GS: Durable Regression of Primary Cutaneous B-cell Lymphoma following Fever-inducing Mistletoe Treatment – Two Case Reports. Glob Adv Health Med 2012, 1(1):16-23.

(94) von Schoen-Angerer T, Wilkens J, Kienle GS, Kiene H, Vagedes J: High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series. Perm J 2015, 19(4):76-83.

(95) Kirsch A: Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M). J Altern Complement Med 2007, 13(4):443-445.

(96) Rose A, El-Leithy T, Vom Dorp F, Zakaria A, Eisenhardt A, Tschirdewahn S, Rubben H: Mistletoe Plant Extract in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Phase Ib/IIa Single Group Dose Escalation Study. J Urol 2015, 194(4):939-943.

(97) Kienle GS, Mussler M, Fuchs D, Kiene H: Intravenous Mistletoe Treatment in Integrative Cancer Care: A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors. Evid Based Complement Alternat Med 2016, 2016:4628287.

(98) Kienle GS, Mussler M, Fuchs D, Kiene H: Individualized Integrative Cancer Care in Anthroposophic Medicine: A Qualitative Study of the Concepts and Procedures of Expert Doctors. Integr Cancer Ther 2016.

(99) Sugarman J: Are mistletoe extract injections the next big thing in cancer therapy? Johns Hopkins Magazine 2014, 2016(May 1sts).

(100) Rexer H, Geschaftsstelle der AUO: Study on the treatment of nonmuscle invasive bladder cancer: A phase III efficacy study for intravesical instillation of mistletoe extract in superficial bladder cancer (TIM) AB 40/11 of the AUO. Urologe A 2015, 54(3):406-408.

(101) Kienle GS, Grugel R, Kiene H: Safety of higher dosages of Viscum album L. in animals and humans – a systematic review of immune changes and safety parameters. BMC Complement Altern Med 2011, 11(1):72.

(102) Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F: Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients. EvidBased Complement AlternatMed 2014, 2014:724258.

(103) Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F: Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology. Integr Cancer Ther 2015, 14(2):140-148.

(104) Steele ML, Axtner J, Happe A, Kroz M, Matthes H, Schad F: Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study. Evid Based Complement Alternat Med 2014, 2014:236310.

(105) Stein GM, Pfüller U, Schietzel M, Büssing A: Toxic proteins from European mistletoe (Viscum album L. ): increase of intracellular IL-4 but a decrease of IFN- g in apoptotic cells. Anticancer Res 2000, 20(3A):1673-1678.

(106) Stein GM, Berg PA: Adverse effects during therapy with mistletoe extracts. In: Mistletoe The Genus Viscum end. Edited by Büssing A. Amsterdam: Hardwood Academic Publishers; 2000: 195-208.

Leave a Reply

Your email address will not be published.