scholarly journals European Mistletoe (Viscum album) Extract Is Cytotoxic to Canine High-Grade Astrocytoma Cells In Vitro and Has Additive Effects with Mebendazole

2022 ◽  
Vol 9 (1) ◽  
pp. 31
Author(s):  
Anna Wright ◽  
Rie Watanabe ◽  
Jey W. Koehler

Malignant gliomas are associated with extremely poor clinical outcomes in both humans and dogs, and novel therapies are needed. Glioma-bearing canine patients may serve as promising preclinical models for human therapies, including complementary medicine. The objective of this study was to evaluate the effects of mistletoe extract (Viscum album) alone and in combination with mebendazole in an in vitro model of canine high-grade astrocytoma using the cell line SDT-3G. SDT-3G cells were exposed to a range of concentrations of mistletoe extract alone to obtain an IC50. In separate experiments, cells were exposed to mebendazole at a previously determined IC50 (0.03 µM) alone or in conjunction with varying concentrations of mistletoe extract to determine the additive effects. The IC50 for mistletoe alone was 5.644 ± 0.09 SD μg/mL. The addition of mistletoe at 5 μg/mL to mebendazole at 0.03 µM led to increased cell death compared to what would be expected for each drug separately. The cytotoxicity of mistletoe in vitro and its additive effect with mebendazole support future expanded in vitro and in vivo studies in dogs and supply early evidence that this may be a useful adjunct therapeutic agent for use in glioma-bearing dogs. To the authors’ knowledge, this is the first published report of Viscum album extract in canine glioma.

Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.


1995 ◽  
Vol 268 (5) ◽  
pp. L789-L800 ◽  
Author(s):  
P. G. Phillips ◽  
L. M. Birnby ◽  
A. Narendran

The development of new vessels (angiogenesis) is essential to wound healing. The center of a wound space is hypoxic, a condition that has been shown to stimulate angiogenesis in animal models of coronary artery occlusion. Because the mechanisms involved in this complex process are difficult to study in situ, an in vitro model would provide a useful complement to in vivo studies. This laboratory has developed and characterized calf pulmonary microvessel endothelial cell (PMVEC) cultures and an in vitro model system of angiogenesis using collagen three-dimensional gels that permit migration of cells into vessel networks. This system was used to study the direct effect of normoxia (20% O2) or hypoxia (5% O2) on PMVEC ability to undergo angiogenesis in vitro. Major changes leading to formation of capillary-like networks occurred during the first 3 days of hypoxic exposure only and included restructuring of actin filament networks, focal changes in distribution of basic fibroblast growth factor, and orientation and migration of cell tracts into a collagen gel matrix to form vessel networks.


2017 ◽  
Vol 3 (2) ◽  
pp. 465-468
Author(s):  
Christoph Brandt-Wunderlich ◽  
Lucas Almstädt ◽  
Sebastian Kaule ◽  
Thomas Reske ◽  
Wolfram Schmidt ◽  
...  

AbstractDrug coated balloons (DCB) are used in the therapy of coronary as well as peripheral artery disease. The success of drug transfer to the vessel wall depends on the excipient used in combination with paclitaxel as antiproliferative drug. Although in-vivo studies show very good results with this technology, there is a lack of in-vitro test methods for characterization of various DCB available on the market. This study describes a method to gain information about the drug transfer and the particle release of three different DCB based on cetylpyridinium salycate (Cetpyrsal), hyaluronic acid and iopromide within a porcine in-vitro model. The Cetpyrsal-based DCB showed promising results with the highest drug transfer while producing the lowest number of particles.


Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 161 ◽  
Author(s):  
Terezia Kiskova ◽  
Peter Kubatka ◽  
Dietrich Büsselberg ◽  
Monika Kassayova

Despite intensive research, malignant brain tumors are among the most difficult to treat due to high resistance to conventional therapeutic approaches. High-grade malignant gliomas, including glioblastoma and anaplastic astrocytoma, are among the most devastating and rapidly growing cancers. Despite the ability of standard treatment agents to achieve therapeutic concentrations in the brain, malignant gliomas are often resistant to alkylating agents. Resveratrol is a plant polyphenol occurring in nuts, berries, grapes, and red wine. Resveratrol crosses the blood‒brain barrier and may influence the central nervous system. Moreover, it influences the enzyme isocitrate dehydrogenase and, more importantly, the resistance to standard treatment via various mechanisms, such as O6-methylguanine methyltransferase. This review summarizes the anticancer effects of resveratrol in various types of brain cancer. Several in vitro and in vivo studies have presented promising results; however, further clinical research is necessary to prove the therapeutic efficacy of resveratrol in brain cancer treatment.


1996 ◽  
Vol 40 (10) ◽  
pp. 2258-2261 ◽  
Author(s):  
S Schwank ◽  
J Blaser

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.


1990 ◽  
Vol 259 (1) ◽  
pp. G134-G139 ◽  
Author(s):  
W. Inauen ◽  
D. N. Granger ◽  
C. J. Meininger ◽  
M. E. Schelling ◽  
H. J. Granger ◽  
...  

The major objective of this study was to develop an in vitro model of ischemia/reperfusion (I/R)-induced microvascular injury. Cultured venular endothelial cells were grown to confluency, labeled with 51Cr, and exposed to different durations of anoxia (0.5, 1, 2, 3, and 4 h). 51Cr release and cell detachment (indexes of cell injury) were determined at different times after reoxygenation (1, 2, 4, 6, 8, and 18 h). Because in vivo studies have implicated neutrophils in I/R injury, in some experiments human neutrophils were added to the endothelial cells upon reoxygenation. Periods of anoxia greater than or equal to 2 h resulted in 70-80% 51Cr release and 80-95% cell detachment upon reoxygenation. Under these conditions (near maximal injury), the addition of neutrophils produced negligible effects. Periods of anoxia less than or equal to 1 h resulted in 30-40% 51Cr release and 50-60% cell detachment. Under these conditions (moderate cell injury), addition of neutrophils enhanced endothelial cell injury. Using a 30-min period of anoxia, we also assessed the effects of superoxide dismutase (SOD; 300 U/ml) and allopurinol (20 microM) on anoxia/reoxygenation (A/R)-induced injury in the presence or absence of neutrophils. In the absence of neutrophils, SOD or allopurinol did not protect against A/R-induced injury. However, in the presence of neutrophils, both SOD and allopurinol attenuated the increases in 51Cr release. The results derived using this in vitro model of I/R injury are largely consistent with published in vivo studies. Thus this in vitro model may provide further insights regarding the mechanisms involved in I/R injury.


2000 ◽  
Vol 68 (4) ◽  
pp. 1912-1918 ◽  
Author(s):  
Catherine S. McVay ◽  
Peter Bracken ◽  
Lucille F. Gagliardo ◽  
Judith Appleton

ABSTRACT Infection with the parasitic nematode Trichinella spiralis is initiated when the L1 larva invades host intestinal epithelial cells. Monoclonal antibodies specific for glycans on the larval surface and secreted glycoproteins protect the intestine against infection. Protective antibodies recognize tyvelose which caps the target glycan. In this study, we used an in vitro model of invasion to further examine the mechanism(s) by which tyvelose-specific antibodies protect epithelial cells against T. spiralis. Using cell lines that vary in susceptibility to invasion, we confirmed and clarified the results of our in vivo studies by documenting three modes of interference: exclusion of larvae from cells, encumbrance of larvae as they migrated within epithelial monolayers, and inhibition of parasite development. Excluded larvae bear cephalic caps (C. S. McVay et al., Infect. Immun. 66:1941–1945, 1998) of immune complexes that may physically block invasion or may interfere with sensory reception. Monovalent Fab fragments prepared from a tyvelose-specific antibody also excluded larvae from cells, demonstrating that antibody binding can inhibit the parasite in the absence of antigen aggregation and cap formation. In contrast, encumbered larvae caused extensive damage to the monolayer yet were not successful in establishing a niche, as reflected by their failure to molt. These results show that antibodies to tyvelose exhibit multiple modes of inhibitory activity, further implicating tyvelose-bearing glycoproteins as mediators of invasion and niche establishment by T. spiralis.


2004 ◽  
Vol 82 (2) ◽  
pp. 146-152 ◽  
Author(s):  
B Lambert ◽  
L De Ridder ◽  
G Slegers ◽  
V de Gelder ◽  
R A Dierckx ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.Key words: hepatocellular carcinoma, cisplatin, gemcitabine, 5-fluorouracil, gamma irradiation.


2019 ◽  
Vol 8 (12) ◽  
pp. 2214 ◽  
Author(s):  
Carl Fisher ◽  
Girgis Obaid ◽  
Carolyn Niu ◽  
Warren Foltz ◽  
Alyssa Goldstein ◽  
...  

Background: Malignant gliomas are highly invasive and extremely difficult to treat tumours with poor prognosis and outcomes. Photodynamic therapy (PDT), mediated by Gleolan®, has been studied previously with partial success in treating these tumours and extending lifetime. We aim to determine whether combining PDT using ALA-protoporphyrin IX (PpIX) with a liposomal formulation of the clinical epidermal growth factor receptor (EGFR) inhibitor, lapatinib, would increase the anti-tumour PDT efficacy. Methods: Lapatinib was given in vitro and in vivo 24 h prior to PDT and for 3–5 days following PDT to elicit whether the combination provided any benefits to PDT therapy. Live-cell imaging, in vitro PDT, and in vivo studies were performed to elucidate the effect lapatinib had on PDT for a variety of glioma cell lines and as well as GSC-30 neurospheres in vivo. Results: PDT combined with lapatinib led to a significant increase in PpIX accumulation, and reductions in the LD50 of PpIX mediated PDT in two EGFR-driven cell lines, U87 and U87vIII, tested (p < 0.05). PDT + lapatinib elicited stronger MRI-quantified glioma responses following PDT for two human glioma-derived tumours (U87 and GSC-30) in vivo (p < 0.05). Furthermore, PDT leads to enhanced survival in rats following treatment with lapatinib compared to lapatinib alone and PDT alone (p < 0.05). Conclusions: As lapatinib is approved for other oncological indications, a realization of its potential combination with PDT and in fluorescence-guided resection could be readily tested clinically. Furthermore, as its use would only be in acute settings, long-term resistance should not pose an issue as compared to its use as monotherapy.


Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 268 ◽  
Author(s):  
Mariangela Centrone ◽  
Patrizia Gena ◽  
Marianna Ranieri ◽  
Annarita Di Mise ◽  
Mariagrazia D’Agostino ◽  
...  

Dietary habits are crucially important to prevent the development of lifestyle-associated diseases. Diets supplemented with chickpeas have numerous benefits and are known to improve body fat composition. The present study was undertaken to characterize two genetically and phenotypically distinct accessions, MG_13 and PI358934, selected from a global chickpea collection. Rat hepatoma FaO cells treated with a mixture of free fatty acids (FFAs) (O/P) were used as an in vitro model of hepatic steatosis. In parallel, a high-fat diet (HFD) animal model was also established. In vitro and in vivo studies revealed that both chickpea accessions showed a significant antioxidant ability. However, only MG_13 reduced the lipid over-accumulation in steatotic FaO cells and in the liver of HFD fed mice. Moreover, mice fed with HFD + MG_13 displayed a lower level of glycemia and aspartate aminotransferase (AST) than HFD mice. Interestingly, exposure to MG_13 prevented the phosphorylation of the inflammatory nuclear factor kappa beta (NF-kB) which is upregulated during HFD and known to be linked to obesity. To conclude, the comparison of the two distinct chickpea accessions revealed a beneficial effect only for the MG_13. These findings highlight the importance of studies addressing the functional characterization of chickpea biodiversity and nutraceutical properties.


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