Stimulation of tumor necrosis factor-α, interleukin-1 and interleukin-6 by a galactoside-specific lectin given in clinically applied mistletoe extract induces antitumor activity in patients

Hajtò, Tibor; Hostanska, Katarina

doi:10.1016/1043-4666(91)90286-m

Cited by 44 publications

(83 citation statements)

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“…The lesser secretion of TNF-α might be related to a passive release of cytokines following the secretion of IL-1. These results are consistent with the previous reports on the secretion of cytokines (Hajto et al, 1990;Männel et al, 1991;Hostanska et al, 1995;Riberéau-Gayon et al, 1996;Möckel et al, 1997 Other genes modulated by VCA Among the Fc receptors, the gene coding for FCAR (Fc fragment of IgA receptor) was increased whereas genes coding for FCER1A (Fc fragment of IgE receptor, high affinity I), FCER1G (Fc fragment of IgE receptor, high affinity I, gamma polypeptide), FCGR2C (Fc fragment of IgG receptor, low affinity IIc (CD32)), and FCGRT (Fc fragment of IgG receptor, transporter, alpha) were decreased. Among growth factors, FGF6 (fibroblast growth factor 6), FLT1 (fms-related tyrosine kinase 1), and DTR (diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor)) were increased, and MST1 (macrophage stimulating 1 (hepatocyte growth factor-like)), NRG1 (neuregulin 1), and PDGFD (platelet derived growth factor D) were decreased (Table I and II).…”

Section: Gene Modulation Of Cytokines By Vcasupporting

confidence: 83%

“…In contrast to chemokines, cytokine modulations by mistletoe have been discussed intensively (Hajto et al, 1990;Joshi et al, 1991;Männel et al, 1991;Hostanska et al, 1995;Hostanska et al, 1996;Möckel et al, 1997;Riberéau-Gayon et al, 1997;Yoon et al, 2001). Thirty three genes on the array that code for proteins with cytokine activity were identified.…”

Section: Discussionmentioning

confidence: 99%

“…The most prominent effect of Viscum album extract (VA-E) is their cytotoxic property (Büssing, 2000). There are growing evidence that mistletoe extract can induce apoptotic killing of cultured human tumor cells and lymphocytes (Hajto et al, 1990;Schultze et al, 1991;Park et al, 2001;Urech et al, 2005). Furthermore, European mistletoe lectin (Viscum album L. agglutinin, VAA) was found to modulate cells including human lymphocytes, monocytes, neutrophils, and cancer cells (Hostanska et al, 1996;Savoie et al, 2000;Lavastre et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

Lyu¹,

Park

2010

Biomolecules and Therapeutics

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-Korean mistletoe has a variety of biological effects, such as immunoadjuvant activities. This study investigates the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on human T lymphocytes to determine whether VCA acts as an immunomodulator. Purified human T-lymphocytes were cultured with VCA and RNA from each point was analyzed using Affymetrix human genome chips containing 22,500 probe sets which represents more than 18,000 transcripts derived from 14,500 human genes. As a result, there was a striking upregulation of genes coding for chemokines. Seventeen genes out of 50 coding for proteins with chemokine activity were upregulated including CXCL9 and IL-8 which are related to the treatment of cancer. In addition, 28 cytokine genes were upregulated including IL-1, IL-6, IL-8, IFN-γ, and TNF-α. Taken together, the data suggest that Korean mistletoe lectin, in parallel with European mistletoe, has an ability to modulate human T cell function.

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Section: Gene Modulation Of Cytokines By Vcasupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

Lyu¹,

Park

2010

Biomolecules and Therapeutics

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“…An alternative view would be that cells exhibiting a`memory' phenotype may be hyperresponsive to several cytokines released in response to ML III. Cytokines such as IL-1, -6 and TNF-a are recognised to be induced by the addition of ML I (Hajto et al, 1990). However, in CD8-enriched cultures treated with ML III, no significant changes in the release of type 1 and type 2-related cytokines, such as interferon-g, IL-12, -4, -5, -10, and TNF-a, as compared to the control samples were observed.…”

Section: Killing Of Cd8mentioning

confidence: 83%

Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

1998

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As reported previously by our group, among the toxic proteins from Viscum album L. only the mistletoe lectins (MLs) induce the apoptotic killing pathway in human lymphocytes. Although one may expect a homogenous distribution of carbohydrate domains on cell surface receptors for the carbohydrate binding B chains of the toxic protein, the sensitivity of cells to these B chains obviously differ. Here we report a selective killing of CD8 + CD62L lo cells from healthy individuals by the galNAcspecific ML III (and RCA 60 , which binds to gal and galNAc), while the gal-specific ML I was less effective. This selective killing is not sufficiently explained by protein synthesis inhibition alone, since this subset was not affected by other ribosome inhibiting proteins such as the lectin from Ricinus communis (RCA 120

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“…The lectin components increase the total number and the activities of neutrophils, NK cells and large granular lymphocytes as well as they activate simultaneously monocyte-macrophage and helper cell subpopulations. This was associated with higher levels of cytokines such as interleukins IL-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and TNF-a (Hajto et al, 1990, Schultze et al, 1991Beuth et al, 1993).The described immunological effects of mistletoe polysaccharides are supplemented by membrane lipids. As shown by Hartmann et al (1995) isolated vesicles of genuine membrane systems were the most potent stimulating factor for T-cell proliferation of mistletoe extracts (Hartmann et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma

2004

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of patients with HCC remain very poor. This study was conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients with chemotherapy -naïve, advanced hepatocellular carcinoma. 23 patients with unrespectable HCC who had received no prior systemic chemotherapy with objectively measurable tumors were enrolled on this study. The mistletoe preparation for the study is an aqueous injectable solution. It contains one milliliter of viscum fraxini in dilution stage -2 (15 mg extract of 20 mg mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate, ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules. 2 ampoules of viscum fraxini -2 were administered subcutaneously once weekly. As assessed by conventional imaging criteria, 3 (13.1%) patients have achieved complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%) had progressive disease while 9 (39.1%) patients didn't have evaluation of response due to early death. The median overall survival time for all patients was 5 months (range 2 -38 months), for those who achieved a CR was 29 months (range 12 -38 months) and, for those who achieved a PR was 6.5 months (range 6 -7 months). The median progression free survival for all patients was 2 months (range 1 -38 months), for those who achieved a CR, it was 29 months (range 8 -38 months) and for those who achieved a partial response, it was 5 months (range 4 -6 months). No hematologic toxicity has been encountered. The spectrum of non-hematologic toxicity was mild. The WHO toxicity criteria grade 3 -4 were 34.8% drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of injection. No drug related discontinuation or toxic deaths have occurred. Viscum fraxini-2 seems to be particularly promising in patients with advanced HCC, it shows antitumor activity and low toxicity profile. Further studies in combination with other active agents are clearly warranted.

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Stimulation of tumor necrosis factor-α, interleukin-1 and interleukin-6 by a galactoside-specific lectin given in clinically applied mistletoe extract induces antitumor activity in patients

Cited by 44 publications

References 0 publications

Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma

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