The immune-system -stimulating and cytotoxic properties of mistletoe have been investigated in laboratory and animal studies.

Viscotoxins and lectins have been investigated as active components in mistletoe; however, most research has focused on the lectins.[1-36] Reviewed in [37-42] Purified mistletoe lectins have demonstrated cytotoxic and immune-system-stimulating activities. To date, four different lectins: ML-1, ML-2, ML-3, and Viscum album chitin -binding agglutinin have been identified in mistletoe extracts. ML-1 (or viscumin) may be responsible for many of mistletoe’s biological effects. When a laboratory method was used to selectively deplete ML-1 from Viscum album extracts, their cytotoxic and immune-system-stimulating properties were markedly reduced.[7,23] It should be noted that fermentation eliminates most of the ML-1 in mistletoe extracts.[43] Reviewed in [44,45]

The molecular structure of ML-1 consists of an alpha chain and a beta chain, which can be separated from one another.[8,9,15,29,31] Reviewed in [46,5,8,19,37,22,38,39,44,47,41,30,21,42,45,32,35,36] Each chain type appears to mediate a subset of the activities described for the intact lectin. Cytotoxicity is associated mainly with the alpha chain. In laboratory studies, the ML-1 alpha chain has been coupled to monoclonal antibodies to produce immunotoxins that target and kill specific cell types.[48,49] Reviewed in [38]

Recombinant ML-1, rML (also known as rViscunim or aviscumin) appears to have the same efficacy as plant-based ML-1 in laboratory studies.[50] Since this is not an extract of mistletoe, it is out of the purview of this summary.

The beta chain of ML-1 is responsible for binding to the surface of a target cell.[51] Studies of mistletoe lectin binding to cancer cells have examined whether the extent of cell binding can predict disease outcome or survival. Studies show that the prognostic value of ML-1 binding depends on the type of cancer.[52] For human breast cancer cells, the amount of lectin-bound cells correlates positively with disease outcome. However, for human adenocarcinoma of the lung, there is no correlation between the amount of lectin-bound cells and disease survival.[53] Though much research has looked at this particular aspect, there have not been studies that directly link the concentration of that component to any clinical activity of mistletoe.

Laboratory studies have shown that mistletoe extracts can stimulate the activity of white blood cells in vitro and cause them to release molecules thought to be important for anticancer immune responses.[54,11,15,16,19,20,22,55-57] Reviewed in [9,28,35,37,38,41,58-60] In addition, mistletoe extracts have demonstrated cytotoxic activity against a variety of mouse, rat, and human cancer cells in vitro.[3,1,2,4,61,62,46,63,5-7,64,65,8,66,30,31,51,67,68] Reviewed in [37,69,47]

There are conflicting reports concerning the stimulation of cancer cell growth in vitro. In one study, the in vitro growth of several types of human cancer cells was stimulated by treatment with low doses of the purified lectin ML-1.[8] However, two subsequent studies found that ML-1 did not induce cell proliferation.[70,71]

A 2004 in vitro study of IscadorQu, a fermented aqueous extract from European mistletoe grown on oaks, against various cell lines demonstrated that sensitivity to this extract varies greatly among cell lines. In sensitive cell lines, a strong effect was seen in epidermal (HaCaT), lung adenocarcinoma (NCI-H125), and breast adenocarcinoma (MCF-7) cell lines whereas, little or no effect was seen in lung squamous cell carcinoma (MR65) and colon carcinoma (Cac0-2, HT-29). Some cells lines were responsive to high or low concentrations of IscadorQu. IscadorQu showed early cell cycle inhibition followed by apoptosis in a dose-dependent manner.[72]

Studies of the ability of mistletoe to inhibit cancer cell growth in animals have yielded mixed and inconsistent results.[1,62-64,73,33,34,74,35,36,75,76,67] Reviewed in [37,47,41,77] In most of these studies, mistletoe extracts were administered either by subcutaneous injection or by intraperitoneal injection.

In one animal study, treatment with IscadorM increased the survival time of mice that had been implanted with Ehrlich ascites mouse cancer cells, but not L1210 leukemia or B16 melanoma cancer cells.[1] The effect of IscadorM on the growth of tumors formed in mice by three additional types of mouse cancer cells (i.e., Lewis lung carcinoma, colon adenocarcinoma 38, and C3H mammary adenocarcinoma) was also assessed in this study. Treatment with IscadorM substantially reduced the growth rate of all three types of tumors.

In another animal study, mice were administered IscadorM before, during, or after injection with either of two types of mouse cancer cells (i.e., Dalton lymphoma or Ehrlich ascites).[63] In this study, all groups of mice treated with mistletoe showed substantially slower tumor growth than the control groups.

No antitumor effect or improvement in survival was observed when IscadorM was used to treat rats bearing chemically induced mammary carcinomas or tumors formed from rat Walker 256 carcinosarcoma cells.[75] In this study, IscadorM was also not effective in treating mice that had been injected with Ehrlich ascites cells. In addition, IscadorP was found ineffective in treating rats with tumors formed from rat L5222 leukemia cells.

In another study, intratumoral injections of mistletoe extract (ABNOBAviscum Fraxini-2) demonstrated more antitumor activity than intravenous gemcitabine when injected into mouse xenografts of human pancreatic cancer.[78]

Treatment with the mistletoe extract Lektinol (also sold as Plenosol; refer to the General Information ¹ section of this summary for more information) has likewise yielded mixed results in animal experiments.[36] Treatment with Lektinol slowed the growth of tumors formed in mice from implants of three types of mouse cancer (i.e., colon adenocarcinoma 38, Renca renal cell carcinoma, and F9 testicular carcinoma) but not in two other mouse cancers (i.e., B16 melanoma and Lewis lung carcinoma).

The anticancer effects of Isorel (also sold as Vysorel; refer to the General Information ¹ section of this summary for more information) have been examined in at least two animal studies.[64,67] In one study, IsorelM was used alone or in combination with local x-ray therapy in mice bearing mouse CMC-2 fibrosarcoma tumors.[64] When IsorelM was used alone, no effect on either tumor growth or animal survival was observed. When IsorelM injections were combined with local x-ray therapy of tumors, substantial improvements in survival were found in comparison to the survival of mice treated with local x-ray therapy alone. With local x-ray therapy alone, 22% of mice were cured of their tumors. When local x-ray therapy was combined with IsorelM injections, administered before or after the x-ray treatment, the cure rate increased to 43%. When IsorelM was administered both before and after local x-ray therapy, the proportion of cured mice increased to 67%.

In another study, IsorelM showed antitumor and antimetastatic effects in mice that had been injected with mouse mammary carcinoma cells.[67] The antitumor effects appeared most pronounced when IsorelM was injected in the vicinity of tumors.

The ability of purified or recombinant lectin ML-1 to inhibit the formation of chemically induced bladder tumors in rats has been evaluated in three studies.[33,34,76] Reviewed in [37] In two of the studies, purified ML-1 was administered by subcutaneous injection.[33,34] Reviewed in [37] Treatment with ML-1 did not reduce the frequency of bladder tumor formation or increase immune system activity in the bladder wall in either study. In the third study, recombinant ML-1 was introduced directly into the bladder through a process known as intravesical instillation.[76] Reviewed in [37] In this study, the frequency of bladder tumor formation was reduced by approximately 50% in ML-1-treated animals. As in the other two studies, immune system activity in the bladder wall was not increased substantially. It was concluded that the antitumor effect observed in this study was the result of direct cytotoxic action by the recombinant lectin against malignant cells.[76]

A few animal studies have suggested that mistletoe is beneficial in decreasing the side effects of conventional anticancer therapy (e.g., chemotherapy and radiation therapy) and that it counteracts the effects of drugs used to suppress the immune system.[17,79,80] Reviewed in [47] In one study, IscadorM was shown to increase the number of white blood cells in mice treated with cyclophosphamide chemotherapy or radiation therapy and to decrease the amount of weight loss due to radiation, but not during cyclophosphamide treatment.[80] Recombinant mistletoe lectin has also been shown to induce increased apoptosis when combined with x-ray treatment.[81] In another study, IscadorM was shown to accelerate the recovery of hematopoietic tissue in the bone marrow and spleens of irradiated rats and mice.[79] In another study, the mistletoe product Eurixor was shown to counteract the immunosuppressive effects of treatment with the drug cortisone.[17]

References

1. Khwaja TA, Dias CB, Pentecost S: Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology 43 (Suppl 1): 42-50, 1986.  [PUBMED Abstract]
   
   
2. Ribéreau-Gayon G, Jung ML, Baudino S, et al.: Effects of mistletoe (Viscum album L.) extracts on cultured tumor cells. Experientia 42 (6): 594-9, 1986.  [PUBMED Abstract]
   
   
3. Stirpe F, Sandvig K, Olsnes S, et al.: Action of viscumin, a toxic lectin from mistletoe, on cells in culture. J Biol Chem 257 (22): 13271-7, 1982.  [PUBMED Abstract]
   
   
4. Ribéreau-Gayon G, Jung ML, Di Scala D, et al.: Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells. Oncology 43 (Suppl 1): 35-41, 1986.  [PUBMED Abstract]
   
   
5. Walzel H, Jonas L, Rosin T, et al.: Relationship between internalization kinetics and cytotoxicity of mistletoe lectin I to L1210 leukaemia cells. Folia Biol (Praha) 36 (3-4): 181-8, 1990.  [PUBMED Abstract]
   
   
6. Gawlik C, Versteeg R, Engel E, et al.: Antiproliferative effect of mistleotoe-extracts in melanoma cell lines. [Abstract] Anticancer Res 12 (6A): A-364, 1882, 1992. 
   
   
7. 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). Arzneimittelforschung 43 (11): 1221-7, 1993.  [PUBMED Abstract]
   
   
8. Gabius HJ, Darro F, Remmelink M, et al.: Evidence for stimulation of tumor proliferation in cell lines and histotypic cultures by clinically relevant low doses of the galactoside-binding mistletoe lectin, a component of proprietary extracts. Cancer Invest 19 (2): 114-26, 2001.  [PUBMED Abstract]
   
   
9. Franz H: Mistletoe lectins and their A and B chains. Oncology 43 (Suppl 1): 23-34, 1986.  [PUBMED Abstract]
   
   
10. Hajto T, Hostanska K, Gabius HJ: Modulatory potency of the beta-galactoside-specific lectin from mistletoe extract (Iscador) on the host defense system in vivo in rabbits and patients. Cancer Res 49 (17): 4803-8, 1989.  [PUBMED Abstract]
    
    
11. Hajto T, Hostanska K, Frei K, et al.: Increased secretion of tumor necrosis factors alpha, interleukin 1, and interleukin 6 by human mononuclear cells exposed to beta-galactoside-specific lectin from clinically applied mistletoe extract. Cancer Res 50 (11): 3322-6, 1990.  [PUBMED Abstract]
    
    
12. Beuth J, Ko HL, Gabius HJ, et al.: Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients. Clin Investig 70 (8): 658-61, 1992.  [PUBMED Abstract]
    
    
13. Gabius HJ, Walzel H, Joshi SS, et al.: The immunomodulatory beta-galactoside-specific lectin from mistletoe: partial sequence analysis, cell and tissue binding, and impact on intracellular biosignalling of monocytic leukemia cells. Anticancer Res 12 (3): 669-75, 1992 May-Jun.  [PUBMED Abstract]
    
    
14. Beuth J, Ko HL, Tunggal L, et al.: Thymocyte proliferation and maturation in response to galactoside-specific mistletoe lectin-1. In Vivo 7 (5): 407-10, 1993 Sep-Oct.  [PUBMED Abstract]
    
    
15. Timoshenko AV, Gabius HJ: Efficient induction of superoxide release from human neutrophils by the galactoside-specific lectin from Viscum album. Biol Chem Hoppe Seyler 374 (4): 237-43, 1993.  [PUBMED Abstract]
    
    
16. Timoshenko AV, Kayser K, Drings P, et al.: Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy. Anticancer Res 13 (5C): 1789-92, 1993 Sep-Oct.  [PUBMED Abstract]
    
    
17. Beuth J, Ko HL, Tunggal L, et al.: Immunoprotective activity of the galactoside-specific mistletoe lectin in cortisone-treated BALB/c-mice. In Vivo 8 (6): 989-92, 1994 Nov-Dec.  [PUBMED Abstract]
    
    
18. Heiny BM, Beuth J: Mistletoe extract standardized for the galactoside-specific lectin (ML-1) induces beta-endorphin release and immunopotentiation in breast cancer patients. Anticancer Res 14 (3B): 1339-42, 1994 May-Jun.  [PUBMED Abstract]
    
    
19. Timoshenko AV, Gabius HJ: Influence of the galactoside-specific lectin from Viscum album and its subunits on cell aggregation and selected intracellular parameters of rat thymocytes. Planta Med 61 (2): 130-3, 1995.  [PUBMED Abstract]
    
    
20. Timoshenko AV, Cherenkevich SN, Gabius HJ: Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function. Biomed Pharmacother 49 (3): 153-8, 1995.  [PUBMED Abstract]
    
    
21. Sweeney EC, Palmer RA, Pfüller U: Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose. J Mol Biol 234 (4): 1279-81, 1993.  [PUBMED Abstract]
    
    
22. Hostanska K, Hajto T, Spagnoli GC, et al.: A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. Nat Immun 14 (5-6): 295-304, 1995.  [PUBMED Abstract]
    
    
23. Beuth J, Stoffel B, Ko HL, et al.: Immunomodulating ability of galactoside-specific lectin standardized and depleted mistletoe extract. Arzneimittelforschung 45 (11): 1240-2, 1995.  [PUBMED Abstract]
    
    
24. Lenartz D, Stoffel B, Menzel J, et al.: Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 16 (6B): 3799-802, 1996 Nov-Dec.  [PUBMED Abstract]
    
    
25. Heiny BM, Albrecht V, Beuth J: Correlation of immune cell activities and beta-endorphin release in breast carcinoma patients treated with galactose-specific lectin standardized mistletoe extract. Anticancer Res 18 (1B): 583-6, 1998 Jan-Feb.  [PUBMED Abstract]
    
    
26. Lenartz D, Dott U, Menzel J, et al.: Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 20 (3B): 2073-6, 2000 May-Jun.  [PUBMED Abstract]
    
    
27. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al.: The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 37 (1): 23-31, 2001.  [PUBMED Abstract]
    
    
28. Goebell PJ, Otto T, Suhr J, et al.: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168 (1): 72-5, 2002.  [PUBMED Abstract]
    
    
29. Olsnes S, Stirpe F, Sandvig K, et al.: Isolation and characterization of viscumin, a toxic lectin from Viscum album L. (mistletoe). J Biol Chem 257 (22): 13263-70, 1982.  [PUBMED Abstract]
    
    
30. Holtskog R, Sandvig K, Olsnes S: Characterization of a toxic lectin in Iscador, a mistletoe preparation with alleged cancerostatic properties. Oncology 45 (3): 172-9, 1988.  [PUBMED Abstract]
    
    
31. Dietrich JB, Ribéreau-Gayon G, Jung ML, et al.: Identity of the N-terminal sequences of the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-chain ribosome-inhibiting proteins. Anticancer Drugs 3 (5): 507-11, 1992.  [PUBMED Abstract]
    
    
32. Büssing A, Suzart K, Bergmann J, et al.: Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Lett 99 (1): 59-72, 1996.  [PUBMED Abstract]
    
    
33. Kunze E, Schulz H, Gabius HJ: Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration. J Cancer Res Clin Oncol 124 (2): 73-87, 1998.  [PUBMED Abstract]
    
    
34. Kunze E, Schulz H, Adamek M, et al.: Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response. J Cancer Res Clin Oncol 126 (3): 125-38, 2000.  [PUBMED Abstract]
    
    
35. Mengs U, Schwarz T, Bulitta M, et al.: Antitumoral effects of an intravesically applied aqueous mistletoe extract on urinary bladder carcinoma MB49 in mice. Anticancer Res 20 (5B): 3565-8, 2000 Sep- Oct.  [PUBMED Abstract]
    
    
36. Burger AM, Mengs U, Schüler JB, et al.: Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models. Anticancer Res 21 (3B): 1965-8, 2001 May-Jun.  [PUBMED Abstract]
    
    
37. Mengs U, Göthel D, Leng-Peschlow E: Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research. Anticancer Res 22 (3): 1399-407, 2002 May-Jun.  [PUBMED Abstract]
    
    
38. Bocci V: Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. J Biol Regul Homeost Agents 7 (1): 1-6, 1993 Jan-Mar.  [PUBMED Abstract]
    
    
39. Gabius HJ, Gabius S, Joshi SS, et al.: From ill-defined extracts to the immunomodulatory lectin: will there be a reason for oncological application of mistletoe? Planta Med 60 (1): 2-7, 1994.  [PUBMED Abstract]
    
    
40. Kleijnen J, Knipschild P: Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine 1: 255-60, 1994. 
    
    
41. Samtleben R, Hajto T, Hostanska K, et al.: Mistletoe lectins as immunostimulants (chemistry, pharmacology and clinic). In: Wagner H, ed.: Immunomodulatory Agents from Plants. Basel, Switzerland: Birkhauser Verlag, 1999, pp 223-41. 
    
    
42. Friess H, Beger HG, Kunz J, et al.: Treatment of advanced pancreatic cancer with mistletoe: results of a pilot trial. Anticancer Res 16 (2): 915-20, 1996 Mar-Apr.  [PUBMED Abstract]
    
    
43. Wagner H, Jordan E, Feil B: Studies on the standardization of mistletoe preparations. Oncology 43 (Suppl 1): 16-22, 1986.  [PUBMED Abstract]
    
    
44. Mistletoe. In: Murray MT: The Healing Power of Herbs. Roseville, Calif: Prima Publishing, 1995, pp 253-9. 
    
    
45. Jäggy C, Musielski H, Urech K, et al.: Quantitative determination of lectins in mistletoe preparations. Arzneimittelforschung 45 (8): 905-9, 1995.  [PUBMED Abstract]
    
    
46. Jung ML, Baudino S, Ribéreau-Gayon G, et al.: Characterization of cytotoxic proteins from mistletoe (Viscum album L.). Cancer Lett 51 (2): 103-8, 1990.  [PUBMED Abstract]
    
    
47. Zee-Cheng RK: Anticancer research on Loranthaceae plants. Drugs Future 22 (5): 519-30, 1997. 
    
    
48. Wiedłocha A, Sandvig K, Walzel H, et al.: Internalization and action of an immunotoxin containing mistletoe lectin A-chain. Cancer Res 51 (3): 916-20, 1991.  [PUBMED Abstract]
    
    
49. Tonevitsky AG, Toptygin AYu, Pfuller U, et al.: Immunotoxin with mistletoe lectin I A-chain and ricin A-chain directed against CD5 antigen of human T-lymphocytes; comparison of efficiency and specificity. Int J Immunopharmacol 13 (7): 1037-41, 1991.  [PUBMED Abstract]
    
    
50. Habeck M: Mistletoe compound enters clinical trials. Drug Discov Today 8 (2): 52-3, 2003.  [PUBMED Abstract]
    
    
51. Müthing J, Meisen I, Kniep B, et al.: Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin. FASEB J 19 (1): 103-5, 2005.  [PUBMED Abstract]
    
    
52. Fritz P, Dippon J, Kierschke T, et al.: Impact of mistletoe lectin binding in breast cancer. Anticancer Res 24 (2C): 1187-92, 2004 Mar-Apr.  [PUBMED Abstract]
    
    
53. Blonski K, Schumacher U, Burkholder I, et al.: Binding of recombinant mistletoe lectin (aviscumine) to resected human adenocarcinoma of the lung. Anticancer Res 25 (5): 3303-7, 2005 Sep-Oct.  [PUBMED Abstract]
    
    
54. Hamprecht K, Handgretinger R, Voetsch W, et al.: Mediation of human NK-activity by components in extracts of Viscum album. Int J Immunopharmacol 9 (2): 199-209, 1987.  [PUBMED Abstract]
    
    
55. Fischer S, Scheffler A, Kabelitz D: Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in mistletoe-treated cancer patients. Cancer Immunol Immunother 44 (3): 150-6, 1997.  [PUBMED Abstract]
    
    
56. Stein GM, Schaller G, Pfüller U, et al.: Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat. Biochim Biophys Acta 1426 (1): 80-90, 1999.  [PUBMED Abstract]
    
    
57. Stein GM, Schaller G, Pfüller U, et al.: Thionins from Viscum album L: influence of the viscotoxins on the activation of granulocytes. Anticancer Res 19 (2A): 1037-42, 1999 Mar-Apr.  [PUBMED Abstract]
    
    
58. Chernyshov VP, Omelchenko LI, Heusser P, et al.: Immunomodulatory actions of Viscum album (Iscador) in children with recurrent respiratory disease as a result of the Chernobyl nuclear accident. Complementary Therapy and Medicine 5 (3): 141-6, 1997. 
    
    
59. Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996. Complementary Therapy and Medicine 6: 172-7, 1998. 
    
    
60. Hallek M: Interleukin-6-mediated cell growth in multiple myeloma--a role for Viscum album extracts? Onkologie 28 (8-9): 387, 2005.  [PUBMED Abstract]
    
    
61. Hülsen H, Mechelke F: In vitro effectiveness of a mistletoe preparation on cytostatic-drug-resistant human leukemia cells. Naturwissenschaften 74 (3): 144-5, 1987.  [PUBMED Abstract]
    
    
62. Kuttan G, Vasudevan DM, Kuttan R: Isolation and identification of a tumour reducing component from mistletoe extract (Iscador). Cancer Lett 41 (3): 307-14, 1988.  [PUBMED Abstract]
    
    
63. Kuttan G, Vasudevan DM, Kuttan R: Effect of a preparation from Viscum album on tumor development in vitro and in mice. J Ethnopharmacol 29 (1): 35-41, 1990.  [PUBMED Abstract]
    
    
64. Jurin M, Zarković N, Hrzenjak M, et al.: Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. Oncology 50 (6): 393-8, 1993 Nov-Dec.  [PUBMED Abstract]
    
    
65. Schaller G, Urech K, Giannattasio M: Cytotoxicity of different viscotoxins and extracts from the European subspecies Viscum album L. Phytother Res 10 (6): 473-7, 1996. 
    
    
66. Maier G, Fiebig HH: Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro. Anticancer Drugs 13 (4): 373-9, 2002.  [PUBMED Abstract]
    
    
67. Zarkovic N, Vukovic T, Loncaric I, et al.: An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm 16 (1): 55-62, 2001.  [PUBMED Abstract]
    
    
68. Zuzak TJ, Rist L, Eggenschwiler J, et al.: Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations. Anticancer Res 26 (5A): 3485-92, 2006 Sep-Oct.  [PUBMED Abstract]
    
    
69. Capernaros Z: The golden bough: the case for mistletoe. Eur J Herbal Med 1 (1):19-24, 1994. 
    
    
70. Braun JM, Blackwell CC, Weir DM, et al.: Cytokine release of whole blood from adult female donors challenged with mistletoe lectin-1 standardised mistletoe extract and E. coli endotoxin or phytohaemagglutinin (PHA). Anticancer Res 23 (2B): 1349-52, 2003 Mar-Apr.  [PUBMED Abstract]
    
    
71. Burger AM, Mengs U, Kelter G, et al.: No evidence of stimulation of human tumor cell proliferation by a standardized aqueous mistletoe extract in vitro. Anticancer Res 23 (5A): 3801-6, 2003 Sep-Oct.  [PUBMED Abstract]
    
    
72. Harmsma M, Grommé M, Ummelen M, et al.: Differential effects of Viscum album extract IscadorQu on cell cycle progression and apoptosis in cancer cells. Int J Oncol 25 (6): 1521-9, 2004.  [PUBMED Abstract]
    
    
73. Nienhaus J, Stoll M, Vester F: Thymus stimulation and cancer prophylaxis by Viscum proteins. Experientia 26 (5): 523-5, 1970.  [PUBMED Abstract]
    
    
74. Kuttan G: Tumoricidal activity of mouse peritoneal macrophages treated with Viscum album extract. Immunol Invest 22 (6-7): 431-40, 1993 Aug-Oct.  [PUBMED Abstract]
    
    
75. Berger M, Schmähl D: Studies on the tumor-inhibiting efficacy of Iscador in experimental animal tumors. J Cancer Res Clin Oncol 105 (3): 262-5, 1983.  [PUBMED Abstract]
    
    
76. Elsässer-Beile U, Ruhnau T, Freudenberg N, et al.: Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary bladder carcinogenesis in a rat model. Cancer 91 (5): 998-1004, 2001.  [PUBMED Abstract]
    
    
77. Stauder H, Kreuser ED: Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie 25 (4): 374-80, 2002.  [PUBMED Abstract]
    
    
78. Rostock M, Huber R, Greiner T, et al.: Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts. Anticancer Res 25 (3B): 1969-75, 2005 May-Jun.  [PUBMED Abstract]
    
    
79. Rentea R, Lyon E, Hunter R: Biologic properties of iscador: a Viscum album preparation I. Hyperplasia of the thymic cortex and accelerated regeneration of hematopoietic cells following X-irradiation. Lab Invest 44 (1): 43-8, 1981.  [PUBMED Abstract]
    
    
80. Kuttan G, Kuttan R: Reduction of leukopenia in mice by "viscum album" administration during radiation and chemotherapy. Tumori 79 (1): 74-6, 1993.  [PUBMED Abstract]
    
    
81. Hostanska K, Vuong V, Rocha S, et al.: Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation. Br J Cancer 88 (11): 1785-92, 2003.  [PUBMED Abstract]
    
    

Glossary Terms

Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

A substance that makes particles (such as bacteria or cells) stick together to form a clump or a mass.

Having to do with stopping abnormal cell growth.

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

Abnormal buildup of fluid in the abdomen that may cause swelling. In late-stage cancer, tumor cells may be found in the fluid in the abdomen. Ascites also occurs in patients with liver disease.

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

Cancer that begins in the skin or in tissues that line or cover internal organs.

A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat).

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

A type of polysaccharide (sugar molecule) that is made by some plants and animals. The hard outer shell of shrimp, lobsters, and many insects is made of chitin.

The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses.

An anticancer drug that belongs to the family of drugs called alkylating agents.

Cell-killing.

The amount of medicine taken, or radiation given, at one time.

In medicine, a preparation of a substance obtained from plants, animals, or bacteria and used as a drug or in drugs.

A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place.

Tissue in which new blood cells are formed.

The complex group of organs and cells that defends the body against infections and other diseases.

Describes the ability to decrease the body's immune system responses.

An antibody linked to a toxic substance. Some immunotoxins can bind to cancer cells and kill them.

In the laboratory (outside the body). The opposite of in vivo (in the body).

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

In medicine, a method used to put a liquid into the body slowly or drop by drop.

Within the peritoneal cavity (the area that contains the abdominal organs). Also called IP.

Within the bladder.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

Having to do with the breast.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

Having to do with metastasis, which is the spread of cancer from one part of the body to another.

A semiparasitic plant that grows on some types of trees. Mistletoe extracts are being studied as treatments for cancer.

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

In genetics, describes DNA, proteins, cells, or organisms that are made by combining genetic material from two different sources. Recombinant substances are made in the laboratory and are being studied in the treatment of cancer and for many other uses.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Beneath the skin.

A member of a group of small proteins produced by mistletoe plants that are able to kill cells and may stimulate the immune system.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.

A type of radiation therapy that uses high-energy radiation from x-rays to kill cancer cells and shrink tumors.