Phytotherapeutic Immunomodulation as a Treatment Modality in Oncology: Lessons from Research with Mistletoe

Gabius, Hans‐Joachim; Gabius, Sigrun

doi:10.1021/bk-1998-0691.ch019

Cited by 4 publications

(4 citation statements)

References 33 publications

(36 reference statements)

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“…Therein, monitoring of the course of disease after chemically induced bladder carcinogenesis accompanied by lectin treatment in the immunomodulatory regimen was reported (45)(46)(47). Since the availability of proinflammatory cytokines is increased in the local microenvironment of responder cells and in serum by ng lectin quantities (11)(12)(13)(14)(15), the potential for cytokinedependent growth augmentation deserves attention (7,26,(50)(51)(52). But the indications for more frequent incidence of tumors with invasive growth after an experimental period of 6 months and of tumors of increased size after an experimental period of 15 months ( p = 0.02) in conjunction with lectin injections s.c. support our evidence for a possibility of promotion of malignant proliferation even in vivo (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

“…Despite of a lack of compelling scientific evidence for clinical efficacy and safety, these methods have received a notable public interest and even acceptance (3)(4)(5). An example is the application of mistletoe extracts, which has its roots in the spiritual reasoning system of anthroposophy intuitively established by Rudolf Steiner in the second and third decades of this century as well as in herbal medicine (6,7). When scouring the evidence-based records for clinical support of the purported oncological merit, the methodological standard of the available material was considered to be "disappointingly poor" and the evidence for a benefit "weak and inconclusive" (1,(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…From a lectin dosage of 5-10 ng/ml upward, the lectin acts as a cytostatic agent by triggering apoptosis and necrosis, the A-chain of the AB-protein acting as potent site-specific 28S rRNA N-glycosidase to irreversibly inactivate ribosomes (18)(19)(20). Since the view that immunomodulation is invariably beneficial for the course of a disease is undoubtedly flawed in view of possible ambivalent actions of cytokines (7,11,(25)(26)(27), and the lectin's performance as cytostatic agent warrants further investigation, we have addressed the following questions in this study: Is there an indication for a cell type selectivity of cell binding and/or the cytostatic mechanism? However, postbinding events may govern the actual sensitivity to the cell growth-inhibitory action of the lectin.…”

Section: Introductionmentioning

confidence: 99%

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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

Gabius¹,

Darro²,

Remmelink³

et al. 2001

Cancer Investigation

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The toxic galactoside-specific lectin from mistletoe, a component of proprietary extracts with unproven efficacy in oncology, exhibits capacity to trigger enhanced secretion of proinflammatory cytokines at low doses (ng/ml or ng/kg body weight) and reductions of cell viability with increasing concentrations. To infer any tumor selectivity of this activity, cytofluorimetric and cell growth assays with a variety of established human tumor cell lines were performed. Only quantitative changes were apparent, and the toxicity against tumor cells was within the range of that of the tested fibroblast preparations from 5 donors. No indication for any tumor selectivity was observed. In kinetic studies with 8 sarcoma and 4 melanoma lines, this evidence for quantitative variability of the response in interindividual comparison was further underscored. At 50 pg lectin/ml x 10(5) cells, even a growth-stimulatory impact was noted in 5 of 12 tested cases. To mimic in vivo conditions with presence of cytokine-secreting inflammatory and stromal cells, exposure to the lectin was extended to histotypic cultures established from 30 cases of surgically removed tumor. As salient result, 5 specimens from 4 of the 8 tested tumor classes responded with a significant increase of [3H]-thymidine incorporation relative to controls during the culture period of 72 hours, when the lectin was present at a concentration in the described immunomodulatory range (1 ng/ml). A relation of this activity to the extent of the actual proliferative status of the reactive samples could not be delineated. Therefore, a non-negligible percentage of the established tumor cell lines (e.g., 3 from 8 sarcoma lines) can be markedly stimulated by the lectin at a very low dose and with dependence on the cell type. Furthermore, the feasibility to elicit a significant growth enhancement is likewise documented for human tumor explants in 16.6% of the examined cases. In view of the uncontrolled application of lectin-containing extracts in alternative/complementary medicine, the presented results on unquestionably adverse lectin-dependent effects in two culture systems call for rigorous examination of the clinical safety of this unconventional, scientifically entirely experimental treatment modality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Gabius¹,

Darro²,

Remmelink³

et al. 2001

Cancer Investigation

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“…In addition, viscumin is able to trigger cellular and humoral immune responses within a narrow range of low nontoxic doses (1-2 ng of lectin/kg of body weight) (reviewed in 4). Such an immunomodulatory activity has been claimed to be beneficial in the treatment of cancer as an alternative treatment modality, regardless of the lack of convincing preclinical and clinical data (4,5). Even on the contrary, lectin-triggered immunomodulation can be associated with tumorgrowth-stimulating effects (4,6).…”

mentioning

confidence: 99%