Viscum album é uma planta semiparasita que tem sido usada há séculos para tratar inúmeras doenças humanas, é comumente usado na Europa, onde uma variedade de diferentes extratos são fabricados e comercializados como medicamentos prescritos injetáveis.
O Viscum album é uma das terapias integrativas mais amplamente estudadas para o câncer. Em alguns países europeus, as preparações feitas a partir de Viscum album estão entre as drogas mais prescritas para pacientes com câncer.
O Viscum álbum tem um potencial efeito anticancerígeno, os extratos derivados de Viscum demonstraram matar as células cancerígenas in vitro [ 1-10 ] regulando negativamente os genes centrais envolvidos na progressão do tumor, malignidade, migração e invasão celular como o TGF-β e metaloproteinases de matriz [ 11 , 12 ].
Extratos de Viscum têm reforçado a lise (morte) de células tumorais mediadas por células Natural killer (NK), reduzem o potencial migratório e invasivo de células tumorais e estimulam células do sistema imune tanto in vitro e in vivo [ 10 – 31 ].
Três componentes do Viscum: viscotoxinas , polissacarídeos e lectinas , podem ser os responsáveis por esses efeitos [ 10 , 13 – 15 , 19 – 21 , 23 – 25 , 32 – 39 ].
As Viscotoxinas são pequenas proteínas que exibem atividade de matar células e possível atividade estimuladora do sistema imunológico [ 1 , 6 , 20 , 21 , 40 , 41 ].
As lectinas são moléculas complexas feitas de proteínas e carboidratos que são capazes de se ligar à parte externa das células (por exemplo, células do sistema imunológico) e induzindo alterações bioquímicas neles [ 10 , 42 – 45 ].
Em vista da capacidade do visco de estimular o sistema imunológico, ele foi classificado como um tipo de modificador da resposta biológica [ 42 ]. Modificadores da resposta biológica constituem um grupo diverso de moléculas biológicas que foram usadas individualmente, ou em combinação com outros agentes, para tratar o câncer ou para diminuir os efeitos colaterais de drogas anticâncer. Extratos de Viscum foram demonstrados em ambientes pré-clínicos ter outros mecanismos de ação, tais como antiangiogênese [ 29 ].
As preparações a partir de extratos de Viscum são mais frequentemente usadas no tratamento de pacientes com câncer em países de língua alemã [ 46 ].
Extratos comercialmente disponíveis são comercializados sob uma variedade de marcas, incluindo Iscador, Eurixor, Helixor, Isorel, Iscucina, plenosol e abnobaVISCUM. Alguns extratos são comercializados sob mais de um nome. Iscador, Isorel e Plenosol também são vendidos como Iscar, Vysorel e Lektinol, respectivamente. Todos estes produtos são preparados a partir do Viscum album (Loranthaceae – Viscum album L. ou Viscum europeu).
Além do Viscum europeu, extratos de um tipo de visco coreano ( Viscum album var. Coloratum [Kom.] Ohwi) demonstraram citotoxicidade in vitro e in vivo em estudos de laboratório. [ 47 – 51 ].
O Viscum cresce em vários tipos de árvores, e a composição química dos extratos derivados dele depende das espécies da árvore hospedeira (por exemplo, maçã, olmo, carvalho, pinheiro, álamo e abeto), a época do ano colhida, como a os extratos são preparados, e o produtor comercial. [ 8 , 43 , 52 – 55 ].
Os extratos de Viscum são preparados como soluções aquosas ou soluções de água e álcool, e podem ser fermentados ou não fermentados [ 4 , 6 , 22 , 52 , 53 , 56 – 59 ]. Alguns extratos são preparados de acordo com princípios homeopáticos , e outros não são. Assim, como preparações homeopáticas, elas normalmente não são extratos quimicamente padronizados [ 10 , 60 ]. Além disso, os produtos comerciais podem ser subdivididos de acordo com a espécie da árvore hospedeira, que é tipicamente indicada no nome do produto por uma letra de sufixo. Iscador, um extrato aquoso fermentado de Viscum album L. que é preparado como uma droga homeopática, é comercializado como IscadorM (de macieiras; Malus domestica ), IscadorP (de pinheiros; Pinus sylvestris ), IscadorQu (de carvalhos; Quercus robur ) e IscadorU (de olmo; Ulmus minor ). O Helixor, um extrato aquoso não fermentado de Viscum album L. que é padronizado por seu efeito biológico em células de leucemia humana in vitro, é comercializado como HelixorA (de abetos: Picea abies ), HelixorM (de macieiras) e HelixorP (de pinheiro) [ 57]. Eurixor (que não está mais disponível no mercado para venda), um extrato aquoso não fermentado do Viscum album L., colhido de álamos, é padronizado para conter uma quantidade específica de uma das lectinas do Viscum. (a lectina ML-1) [ 57 ]. Alguns proponentes afirmam que a escolha do extrato deve depender do tipo de tumor e do sexo do paciente [ 55 , 57 61 e 62 ].
Exemplo de indicações do Viscum Helixor:
Exemplo de indicações do Viscum Iscador:
Os extratos de Viscum são geralmente administrados por injeção subcutânea, embora a administração por outras vias (por exemplo, oral , intrapleural , intratumoral e intravenosa) tenha sido descrita [ 19 , 22 – 26 , 39 , 43 , 55 , 57 , 60 , 64 – 70 ]. Na maioria dos estudos relatados, as injeções subcutâneas foram administradas 2 a 3 vezes por semana, mas a duração total do tratamento variou consideravelmente.
Viscum álbum e leucemias
Foi demonstrado pela primeira vez que os triterpenos ou lectinas solubilizados e suas combinações induzem apoptose dose e tempo dependente na linha celular ALL NALM-6 . Com base nos dados in vivo , os autores concluíram que triterpenos contendo extratos de Viscum album L. podem possuir um potencial terapêutico impressionante [71]:
Além disso, foi investigado se os extratos contendo triterpenos também podem induzir apoptose dose-dependente em células primárias de pacientes com leucemia infantil ex vivo . Aqui, também observamos a indução de apoptose, via as vias de sinalização caspase-8 e -9, para viscum, TT e viscumTT.
Camundongos com leucemia foram tratados com extratos de Viscum album L. Os receptores que receberam PBS tiveram um tempo médio de sobrevida de 38 dias, enquanto que o viscumTT prolongou a sobrevivência média para 50,5 dias. Em conjunto, os autores mostraram que essa nova formulação “viscumTT” de extratos aquosos de Viscum e ácidos triterpênicos pode induzir a apoptose em células de leucemia via intrínseca e extrínseca. Além disso, foi revelado um efeito sinérgico para a combinação viscumTT em comparação com o viscum de fração única e TT. Com base nesses dados, os autores acreditam que os extratos de Viscum album L. possui excelente potencial anticâncer [72]:
O tratamento combinado de células de leucemia levou a um sinergismo inibitório em concentrações subapoptóticas de doxorrubicina e redução multiforme dos efeitos citotóxicos em células de controlo saudáveis. O co-tratamento com Viscum album prolongado foi associado com redução do acúmulo de G2 / M e aumento da expressão de marcadores apoptóticos precoces e tardios. Os autores concluíram que Viscum album aumenta a eficácia anti-leucemica de doxorrubicina contra células K562 resistentes ao impedir G2 / M prisão e induzindo a apoptose [73]:
Na Alemanha 58,4% dos pacientes com câncer usam terapias complementares, e destes, 61,6% usam Viscum album – de acordo com estudo multicêntrico transversal feito em diversos hospitais (Weis et al., 1998). Nesse país, Helixor é o terceiro medicamento citostático mais prescrito ambulatorialmente (Schwabe & Paffrath, 2007).
Pacientes com leucemia mieloide crônica (N=30) tiveram prolongamento da mediana de sobrevida pelo acrescimo de Helixor ao Bussulfano (55,7 meses contra 30 meses do grupo controle histórico com fatores prognósticos comparáveis, tratado apenas com Bussulfano) (Gutsch, 1982).
A eficácia do tratamento adjuvante com Helixor em linfoma e leucemia crônica foi analisado em estudo retrospectivo com 700 pacientes (Stumpf et al., 2000): o tratamento adicional com Viscum album resultou em aumento de sobrevida mediana (11,4 anos versus 8,6 anos para os pacientes sem Viscum). Além disso, os pacientes relataram melhora na qualidade de vida. A objeção teórica sobre impactos não favoráveis do uso do Viscum em neoplasias malignas do sistema linfático e hematopoiético é refutada por esse estudo [74].
A leucemia mielóide aguda (LMA) é o segundo tipo mais comum de leucemia nos EUA e na Alemanha. A incidência aumenta com a idade e menos de 10% dos pacientes são crianças. O uso adicional de viscumTT potencia fortemente o efeito anti-tumoral da citarabina. Em resumo, os autores demonstraram que o extrato de viscumTT combinando compostos aquosos de Viscum e ácidos triterpênicos induz a apoptose em células HL-60 através das vias de sinalização intrínseca e extrínseca.O estudo in vivo mostrou um forte efeito terapêutico para o viscumTT comparável ao da citarabina. O efeito potenciador do viscumTT e da citarabina fornece fortes evidências de combinação com agentes quimioterápicos clássicos para alcançar um alto sinergismo de eficácia no tratamento do câncer [75]:
Outros potencias usos para o Viscum album
Entre os fitoquímicos bem descritos e mais ativos identificados no Viscum album estão as lectinas e viscotoxinas, que desempenham um papel substancial no tratamento do câncer por causa de seus efeitos apoptóticos e citotóxicos. Outro grupo de compostos encontrados no Viscum album são os ácidos fenólicos, os fenilpropanóides e os flavonóides com atividades antioxidante e antiinflamatória, que diminuem a pressão arterial. Outros componentes do Viscum incluem triterpenos com propriedades citotóxicas e apoptóticas e fitoesteróis, oligo e polissacarídeos. Extratos da planta, especialmente aquosos, são aplicados na medicina tradicional e oficial, entre outros no tratamento da hipertensão ou artrite. Potencialmente, também pode ser usado como medicamento hepatoprotetor ou sedativo[76]:
Extratos de Viscum album L e lectinas isoladas de Vicum possuem propriedades imunoestimulantes e uma forte atividade citotóxica dose-dependente. Eles são frequentemente usados no tratamento complementar do câncer, principalmente para melhorar a qualidade de vida[77]:
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Referências: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]
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]
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]
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]
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]
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.
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]
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]
Franz H: Mistletoe lectins and their A and B chains.Oncology 43 (Suppl 1): 23-34, 1986. [PUBMED Abstract]
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]
Podlech O, Harter PN, Mittelbronn M, et al.: Fermented mistletoe extract as a multimodal antitumoral agent in gliomas.Evid Based Complement Alternat Med 2012: 501796, 2012. [PUBMED Abstract]
Schötterl S, Hübner M, Armento A, et al.: Viscumins functionally modulate cell motility-associated gene expression.Int J Oncol 50 (2): 684-696, 2017. [PUBMED Abstract]
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]
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]
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]
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]
Preisfeld A: Influence of aqueous mistletoe preparations on humoral immune parameters with emphasis on the cytotoxicity of human complement in breast cancer patients.Forsch Komplementarmed 4 (4): 224-8, 1997.
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.Complement Ther Med 5 (3): 141-6, 1997.
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]
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]
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]
In: Murray MT: The Healing Power of Herbs. Roseville, Calif: Prima Publishing, 1995, pp 253-9.
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]
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]
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]
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]
Saha C, Das M, Stephen-Victor E, et al.: Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4⁺ T Cell Responses.Molecules 21 (7): , 2016. [PUBMED Abstract]
Hegde P, Maddur MS, Friboulet A, et al.: Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.PLoS One 6 (10): e26312, 2011. [PUBMED Abstract]
Elluru SR, VAN Huyen JP, Delignat S, et al.: Antiangiogenic properties of viscum album extracts are associated with endothelial cytotoxicity.Anticancer Res 29 (8): 2945-50, 2009. [PUBMED Abstract]
Elluru SR, Duong van Huyen JP, Delignat S, et al.: Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer.BMC Cancer 8: 161, 2008. [PUBMED Abstract]
Elluru S, Duong Van Huyen JP, Delignat S, et al.: Molecular mechanisms underlying the immunomodulatory effects of mistletoe (Viscum album L.) extracts Iscador.Arzneimittelforschung 56 (6A): 461-6, 2006. [PUBMED Abstract]
Frohne D, Pfander HJ: Viscum album.In: Frohne D, Pfander HJ: Giftpflanzen: ein Handbuch für Apotheker, Ärzte, Toxikologen und Biologen. 3rd rev. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft, 1987, pp 179-80.
Pusztai A, Grant G, Pfuller U, et al.: Nutritional and metabolic effects of mistletoe lectin ML-1 (type 2 RIP) in the rat.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 164-7.
Pusztai A, Grant G, Gelencsér E, et al.: Effects of an orally administered mistletoe (type-2 RIP) lectin on growth, body composition, small intestinal structure, and insulin levels in young rats.J Nutr Biochem 9 (1): 31-6, 1998.
Ewen SWB, Bardocz S, Grant G, et al.: The effects of PHA and mistletoe lectin binding to epithelium of rat and mouse gut.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 221-5.
Pryme IF, Bardocz S, Grant G, et al.: The plant lectins PHA and ML-1 suppress the growth of a lymphosarcoma tumour in mice.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 215-20.
Tubeuf KFv, Neckel G, Marzell H: Monographie der Mistel.Munchen, Berlin: R. Oldenbourg, 1923.
Teuscher E: Viscum album.In: Hansel R, Keller K, Rimpler H, et al.: Hagers Handbuch der Pharmazeutischen Praxis, Vol. 5th ed. Berlin, Germany: Springer-Verlag, 1994, pp 1160-83.
Grossarth-Maticek R, Kiene H, Baumgartner SM, et al.: 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.Altern Ther Health Med 7 (3): 57-66, 68-72, 74-6 passim, 2001 May-Jun. [PUBMED Abstract]
Capernaros Z: The golden bough: the case for mistletoe.Eur J Herbal Med 1 (1):19-24, 1994.
Schrader G, Apel K: Isolation and characterization of cDNAs encoding viscotoxins of mistletoe (Viscum album).Eur J Biochem 198 (3): 549-53, 1991. [PUBMED Abstract]
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]
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.
Abdullaev FI, de Mejia EG: Antitumor effect of plant lectins.Nat Toxins 5 (4): 157-63, 1997. [PUBMED Abstract]
Kilpatrick DC: Mechanisms and assessment of lectin-mediated mitogenesis.Mol Biotechnol 11 (1): 55-65, 1999. [PUBMED Abstract]
Horneber MA, Bueschel G, Huber R, et al.: Mistletoe therapy in oncology.Cochrane Database Syst Rev (2): CD003297, 2008. [PUBMED Abstract]
Khil LY, Kim W, Lyu S, et al.: Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells.World J Gastroenterol 13 (20): 2811-8, 2007. [PUBMED Abstract]
Kim MS, Lee J, Lee KM, et al.: Involvement of hydrogen peroxide in mistletoe lectin-II-induced apoptosis of myeloleukemic U937 cells.Life Sci 73 (10): 1231-43, 2003. [PUBMED Abstract]
Choi SH, Lyu SY, Park WB: Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer cells through dephosphorylation of Akt.Arch Pharm Res 27 (1): 68-76, 2004. [PUBMED Abstract]
Romagnoli S, Fogolari F, Catalano M, et al.: NMR solution structure of viscotoxin C1 from Viscum album species Coloratum ohwi: toward a structure-function analysis of viscotoxins.Biochemistry 42 (43): 12503-10, 2003. [PUBMED Abstract]
Yoon TJ, Yoo YC, Kang TB, et al.: Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells.Arch Pharm Res 26 (10): 861-7, 2003. [PUBMED Abstract]
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]
Jäggy C, Musielski H, Urech K, et al.: Quantitative determination of lectins in mistletoe preparations.Arzneimittelforschung 45 (8): 905-9, 1995. [PUBMED Abstract]
Zee-Cheng RK: Anticancer research on Loranthaceae plants.Drugs Future 22 (5): 519-30, 1997.
Kaegi E: Unconventional therapies for cancer: 3. Iscador.Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (9): 1157-9, 1998. [PUBMED Abstract]
Stein G, Berg PA: Non-lectin component in a fermented extract from Viscum album L. grown on pines induces proliferation of lymphocytes from healthy and allergic individuals in vitro.Eur J Clin Pharmacol 47 (1): 33-8, 1994. [PUBMED Abstract]
Kleijnen J, Knipschild P: Mistletoe treatment for cancer: review of controlled trials in humans.Phytomedicine 1: 255-60, 1994.
Wagner H, Jordan E, Feil B: Studies on the standardization of mistletoe preparations.Oncology 43 (Suppl 1): 16-22, 1986. [PUBMED Abstract]
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]
Mellor D: Mistletoe in homoeopathic cancer treatment.Prof Nurse 4 (12): 605-7, 1989. [PUBMED Abstract]
Fellmer KE: A clinical trial of Iscador: follow-up treatment of irradiated genital carcinomata for the prevention of recurrences.Br Homeopath J 57: 43-7, 1968.
Kjaer M: Mistletoe (Iscador) therapy in stage IV renal adenocarcinoma.A phase II study in patients with measurable lung metastases. Acta Oncol 28 (4): 489-94, 1989. [PUBMED Abstract]
Schöffski P, Riggert S, Fumoleau P, et al.: Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group.Ann Oncol 15 (12): 1816-24, 2004. [PUBMED Abstract]
Matthes HF, Schad F, Buchwald D, et al.: Endoscopic ultrasound-guided fine-needle Injection of Viscum album L. (mistletoe; Helixor M) in the therapy of primary inoperable pancreas cancer: a pilot study.[Abstract] Gastroenterology 128 (Suppl 2): A-T988, A433-A434, 2005.
Matthes HF, Schad F, Schenk G: Viscum album in the therapy of primary inoperable hepatocellular carcinoma (HCC).[Abstract] Gastroenterology 126 (Suppl 2): A-755, A101-A102, 2004.
Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996.Complement Ther Med 6 (4): 172-7, 1998.
Kleeberg UR, Brocker EB, Lejeune F, et al.: Adjuvant trial in melanoma patients comparing rlFN-alpha to rlFN-gamma to Iscador to a control group after curative resection of high risk primary (>=3mm) or regional lymphnode metastasis (EORTC 18871).[Abstract] Eur J Cancer 35 (Suppl 4): A-264, s82, 1999.
Heiny BM, Albrecht V, Beuth J: Stabilization of quality of life with mistletoe lectin-1-standardized extract in advanced colorectal carcinoma.Onkologe 4 (Suppl 1): S35-9, 1998.
Wetzel D, Schäfer M: Results of a randomised placebo-controlled multicentre study with PS76A2 (standardised mistletoe preparation) in patients with breast cancer receiving adjuvant chemotherapy.[Abstract] Phytomedicine 7 (Suppl 2): A-SL-66, 2000.
Cho JS, Na KJ, Lee Y, et al.: Chemical Pleurodesis Using Mistletoe Extraction (ABNOVAviscum(®) Injection) for Malignant Pleural Effusion.Ann Thorac Cardiovasc Surg 22 (1): 20-6, 2016. [PUBMED Abstract].
Catharina I.Delebinski, Sebastian Jaeger, Kristin Kemnitz-Hassanin, Arend von Stackelberg, Günter Henze, Holger N. Lode and Georg Seifert: Therapeutic Efficacy of Natural Compounds From Viscum Album l. In Acute Lymphoblastic Leukemia Blood 2010 116:3261.
Catharina I. Delebinski, Kristin Kemnitz-Hassanin, Sebastian Jaeger, Holger N. Lode, Karl-Heinz Seeger, Guenter Henze and Georg Seifert: A NEW DEVELOPMENT of Triterpene Acids-CONTAINING Extracts FROM Viscum Album L. Displays Synergistic INDUCTION of Apoptosis In Childhood LEUKEMIA Blood 2011 118:4296.
Srdic-Rajic T, et al.: Sensitization of K562 Leukemia Cells to Doxorubicin by the Viscum album Extract. Phytother Res. 2016.
Schlodder D., Gardin N. E. Estudos clínicos com Helixor (Viscum album L.) para o tratamento do câncer. Arte Médica Ampliada Ano XXXI n.1 Outono 2011.
Catharina I. Delebinski; Monika Twardziok; Susann Kleinsimon; Florian Hoff; Katharina Mulsow; Jana Rolff; Sebastian Jäger; Angelika Eggert; Georg Seifert: A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo. August 5, 2015
Nazaruk J, et al. Phytochemical profile and therapeutic potential of Viscum album L. Nat Prod Res. 2016.
Kienle GS, et al. Safety of higher dosages of Viscum album L. in animals and humans–systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011.
Referências: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]
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]
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]
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]
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]
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.
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]
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]
Franz H: Mistletoe lectins and their A and B chains.Oncology 43 (Suppl 1): 23-34, 1986. [PUBMED Abstract]
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]
Podlech O, Harter PN, Mittelbronn M, et al.: Fermented mistletoe extract as a multimodal antitumoral agent in gliomas.Evid Based Complement Alternat Med 2012: 501796, 2012. [PUBMED Abstract]
Schötterl S, Hübner M, Armento A, et al.: Viscumins functionally modulate cell motility-associated gene expression.Int J Oncol 50 (2): 684-696, 2017. [PUBMED Abstract]
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]
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]
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]
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]
Preisfeld A: Influence of aqueous mistletoe preparations on humoral immune parameters with emphasis on the cytotoxicity of human complement in breast cancer patients.Forsch Komplementarmed 4 (4): 224-8, 1997.
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.Complement Ther Med 5 (3): 141-6, 1997.
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]
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]
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]
In: Murray MT: The Healing Power of Herbs. Roseville, Calif: Prima Publishing, 1995, pp 253-9.
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]
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]
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]
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]
Saha C, Das M, Stephen-Victor E, et al.: Differential Effects of Viscum album Preparations on the Maturation and Activation of Human Dendritic Cells and CD4⁺ T Cell Responses.Molecules 21 (7): , 2016. [PUBMED Abstract]
Hegde P, Maddur MS, Friboulet A, et al.: Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.PLoS One 6 (10): e26312, 2011. [PUBMED Abstract]
Elluru SR, VAN Huyen JP, Delignat S, et al.: Antiangiogenic properties of viscum album extracts are associated with endothelial cytotoxicity.Anticancer Res 29 (8): 2945-50, 2009. [PUBMED Abstract]
Elluru SR, Duong van Huyen JP, Delignat S, et al.: Induction of maturation and activation of human dendritic cells: a mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer.BMC Cancer 8: 161, 2008. [PUBMED Abstract]
Elluru S, Duong Van Huyen JP, Delignat S, et al.: Molecular mechanisms underlying the immunomodulatory effects of mistletoe (Viscum album L.) extracts Iscador.Arzneimittelforschung 56 (6A): 461-6, 2006. [PUBMED Abstract]
Frohne D, Pfander HJ: Viscum album.In: Frohne D, Pfander HJ: Giftpflanzen: ein Handbuch für Apotheker, Ärzte, Toxikologen und Biologen. 3rd rev. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft, 1987, pp 179-80.
Pusztai A, Grant G, Pfuller U, et al.: Nutritional and metabolic effects of mistletoe lectin ML-1 (type 2 RIP) in the rat.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 164-7.
Pusztai A, Grant G, Gelencsér E, et al.: Effects of an orally administered mistletoe (type-2 RIP) lectin on growth, body composition, small intestinal structure, and insulin levels in young rats.J Nutr Biochem 9 (1): 31-6, 1998.
Ewen SWB, Bardocz S, Grant G, et al.: The effects of PHA and mistletoe lectin binding to epithelium of rat and mouse gut.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 221-5.
Pryme IF, Bardocz S, Grant G, et al.: The plant lectins PHA and ML-1 suppress the growth of a lymphosarcoma tumour in mice.In: European Cooperation in the Field of Scientific and Technical Research: COST 98: Effects of Antinutrients on the Nutritional Value of Legume Diets. Brussels, Belgium: European Commission, Directorate-General XII, Science, Research and Development, 1998, pp 215-20.
Tubeuf KFv, Neckel G, Marzell H: Monographie der Mistel.Munchen, Berlin: R. Oldenbourg, 1923.
Teuscher E: Viscum album.In: Hansel R, Keller K, Rimpler H, et al.: Hagers Handbuch der Pharmazeutischen Praxis, Vol. 5th ed. Berlin, Germany: Springer-Verlag, 1994, pp 1160-83.
Grossarth-Maticek R, Kiene H, Baumgartner SM, et al.: 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.Altern Ther Health Med 7 (3): 57-66, 68-72, 74-6 passim, 2001 May-Jun. [PUBMED Abstract]
Capernaros Z: The golden bough: the case for mistletoe.Eur J Herbal Med 1 (1):19-24, 1994.
Schrader G, Apel K: Isolation and characterization of cDNAs encoding viscotoxins of mistletoe (Viscum album).Eur J Biochem 198 (3): 549-53, 1991. [PUBMED Abstract]
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]
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.
Abdullaev FI, de Mejia EG: Antitumor effect of plant lectins.Nat Toxins 5 (4): 157-63, 1997. [PUBMED Abstract]
Kilpatrick DC: Mechanisms and assessment of lectin-mediated mitogenesis.Mol Biotechnol 11 (1): 55-65, 1999. [PUBMED Abstract]
Horneber MA, Bueschel G, Huber R, et al.: Mistletoe therapy in oncology.Cochrane Database Syst Rev (2): CD003297, 2008. [PUBMED Abstract]
Khil LY, Kim W, Lyu S, et al.: Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells.World J Gastroenterol 13 (20): 2811-8, 2007. [PUBMED Abstract]
Kim MS, Lee J, Lee KM, et al.: Involvement of hydrogen peroxide in mistletoe lectin-II-induced apoptosis of myeloleukemic U937 cells.Life Sci 73 (10): 1231-43, 2003. [PUBMED Abstract]
Choi SH, Lyu SY, Park WB: Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer cells through dephosphorylation of Akt.Arch Pharm Res 27 (1): 68-76, 2004. [PUBMED Abstract]
Romagnoli S, Fogolari F, Catalano M, et al.: NMR solution structure of viscotoxin C1 from Viscum album species Coloratum ohwi: toward a structure-function analysis of viscotoxins.Biochemistry 42 (43): 12503-10, 2003. [PUBMED Abstract]
Yoon TJ, Yoo YC, Kang TB, et al.: Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells.Arch Pharm Res 26 (10): 861-7, 2003. [PUBMED Abstract]
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]
Jäggy C, Musielski H, Urech K, et al.: Quantitative determination of lectins in mistletoe preparations.Arzneimittelforschung 45 (8): 905-9, 1995. [PUBMED Abstract]
Zee-Cheng RK: Anticancer research on Loranthaceae plants.Drugs Future 22 (5): 519-30, 1997.
Kaegi E: Unconventional therapies for cancer: 3. Iscador.Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (9): 1157-9, 1998. [PUBMED Abstract]
Stein G, Berg PA: Non-lectin component in a fermented extract from Viscum album L. grown on pines induces proliferation of lymphocytes from healthy and allergic individuals in vitro.Eur J Clin Pharmacol 47 (1): 33-8, 1994. [PUBMED Abstract]
Kleijnen J, Knipschild P: Mistletoe treatment for cancer: review of controlled trials in humans.Phytomedicine 1: 255-60, 1994.
Wagner H, Jordan E, Feil B: Studies on the standardization of mistletoe preparations.Oncology 43 (Suppl 1): 16-22, 1986. [PUBMED Abstract]
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]
Mellor D: Mistletoe in homoeopathic cancer treatment.Prof Nurse 4 (12): 605-7, 1989. [PUBMED Abstract]
Fellmer KE: A clinical trial of Iscador: follow-up treatment of irradiated genital carcinomata for the prevention of recurrences.Br Homeopath J 57: 43-7, 1968.
Kjaer M: Mistletoe (Iscador) therapy in stage IV renal adenocarcinoma.A phase II study in patients with measurable lung metastases. Acta Oncol 28 (4): 489-94, 1989. [PUBMED Abstract]
Schöffski P, Riggert S, Fumoleau P, et al.: Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group.Ann Oncol 15 (12): 1816-24, 2004. [PUBMED Abstract]
Matthes HF, Schad F, Buchwald D, et al.: Endoscopic ultrasound-guided fine-needle Injection of Viscum album L. (mistletoe; Helixor M) in the therapy of primary inoperable pancreas cancer: a pilot study.[Abstract] Gastroenterology 128 (Suppl 2): A-T988, A433-A434, 2005.
Matthes HF, Schad F, Schenk G: Viscum album in the therapy of primary inoperable hepatocellular carcinoma (HCC).[Abstract] Gastroenterology 126 (Suppl 2): A-755, A101-A102, 2004.
Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996.Complement Ther Med 6 (4): 172-7, 1998.
Kleeberg UR, Brocker EB, Lejeune F, et al.: Adjuvant trial in melanoma patients comparing rlFN-alpha to rlFN-gamma to Iscador to a control group after curative resection of high risk primary (>=3mm) or regional lymphnode metastasis (EORTC 18871).[Abstract] Eur J Cancer 35 (Suppl 4): A-264, s82, 1999.
Heiny BM, Albrecht V, Beuth J: Stabilization of quality of life with mistletoe lectin-1-standardized extract in advanced colorectal carcinoma.Onkologe 4 (Suppl 1): S35-9, 1998.
Wetzel D, Schäfer M: Results of a randomised placebo-controlled multicentre study with PS76A2 (standardised mistletoe preparation) in patients with breast cancer receiving adjuvant chemotherapy.[Abstract] Phytomedicine 7 (Suppl 2): A-SL-66, 2000.
Cho JS, Na KJ, Lee Y, et al.: Chemical Pleurodesis Using Mistletoe Extraction (ABNOVAviscum(®) Injection) for Malignant Pleural Effusion.Ann Thorac Cardiovasc Surg 22 (1): 20-6, 2016. [PUBMED Abstract].
Catharina I.Delebinski, Sebastian Jaeger, Kristin Kemnitz-Hassanin, Arend von Stackelberg, Günter Henze, Holger N. Lode and Georg Seifert: Therapeutic Efficacy of Natural Compounds From Viscum Album l. In Acute Lymphoblastic Leukemia Blood 2010 116:3261.
Catharina I. Delebinski, Kristin Kemnitz-Hassanin, Sebastian Jaeger, Holger N. Lode, Karl-Heinz Seeger, Guenter Henze and Georg Seifert: A NEW DEVELOPMENT of Triterpene Acids-CONTAINING Extracts FROM Viscum Album L. Displays Synergistic INDUCTION of Apoptosis In Childhood LEUKEMIA Blood 2011 118:4296.
Srdic-Rajic T, et al.: Sensitization of K562 Leukemia Cells to Doxorubicin by the Viscum album Extract. Phytother Res. 2016.
Schlodder D., Gardin N. E. Estudos clínicos com Helixor (Viscum album L.) para o tratamento do câncer. Arte Médica Ampliada Ano XXXI n.1 Outono 2011.
Catharina I. Delebinski; Monika Twardziok; Susann Kleinsimon; Florian Hoff; Katharina Mulsow; Jana Rolff; Sebastian Jäger; Angelika Eggert; Georg Seifert: A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo. August 5, 2015
Nazaruk J, et al. Phytochemical profile and therapeutic potential of Viscum album L. Nat Prod Res. 2016.
Kienle GS, et al. Safety of higher dosages of Viscum album L. in animals and humans–systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011.
Por Ana Rosa Rosa Figueira
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