The Effects of Short-Term Treatment With Levamisole on Cytokines in Volunteers and Cancer-Patients

Debrabander, M; Roels,; Vogels, O.J.M.; B, Demoen; Deridder, R; Jagers, Els; A, Baisier; Doolaege, R; DeCoster, Ryan; Aerts, F.; Vandebroek, J.; Decree, J; Verhaegen, H.; Dewaele, Michael; Distelmans, W; Vanbelle, Sophie; Storme, Guy

doi:10.3892/ijo.1.3.337

Cited by 2 publications

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“…Likewise the anthelminthic drug ( S )-levamisole hydrochloride (Ergamisol ® ; 1 ) [29], [30], which has also been used in the treatment of rheumatoid arthritis [31], [32], as well as an immunostimulant adjuvant in chemotherapy for several types of cancer [33]–[36], was recently shown to exhibit angiogenesis inhibitory activity in vitro and tumor growth inhibition in vivo [37], [38]. The in vitro antiangiogenic effect resembled that of Avastin in several respects, but especially with regard to inhibition of network formation and induction of non-differentiated clusters of cells [38].…”

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confidence: 99%

Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

et al. 2012

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Inhibition of angiogenesis is a promising addition to current cancer treatment strategies. Neutralization of vascular endothelial growth factor by monoclonal antibodies is clinically effective but may cause side effects due to thrombosis. Low molecular weight angiogenesis inhibitors are currently less effective than antibody treatment and are also associated with serious side effects. The discovery of new chemotypes with efficient antiangiogenic activity is therefore of pertinent interest. (S)-Levamisole hydrochloride, an anthelminthic drug approved for human use and with a known clinical profile, was recently shown to be an inhibitor of angiogenesis in vitro and exhibited tumor growth inhibition in mice. Here we describe the synthesis and in vitro evaluation of a series of N-alkylated analogues of levamisole with the aim of characterizing structure–activity relationships with regard to inhibition of angiogenesis. N-Methyllevamisole and p-bromolevamisole proved more effective than the parent compound, (S)-levamisole hydrochloride, with respect to inhibition of angiogenesis and induction of undifferentiated cluster morphology in human umbilical vein endothelial cells grown in co-culture with normal human dermal fibroblasts. Interestingly, the cluster morphology caused by N-methyllevamisole was different than the clusters observed for levamisole, and a third “cord-like” morphology resembling that of the known drug suramin was observed for an aniline-containing derivative. New chemotypes exhibiting antiangiogenic effects in vitro are thus described, and further investigation of their underlying mechanism of action is warranted.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

et al. 2012

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“…It has been reported by researchers that levamisole directs the immune balance to type 1 response by initiating Th1 activation and upregulation of IL5 and TNF-α (30). Debrabander et al (13) identified various cytokines that could be used as monitoring parameters for the potential immunomodulatory mechanism of action of levamisole. These are TNF-α, IL-1β, IL-2 or IL-6.…”

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Comparison of immunomodulatory effects of free and liposomal levamisole administered intraperitoneally to rats

SUSAR,

ÇELEBİ,

ÇELEBİ

et al. 2024

Medycyna Weterynaryjna

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This study aimed to compare the effects of immunomodulatory treatment of rats with free and liposomal levamisole. Liposomes were freshly prepared and administered intraperitoneally to animals after characterization studies. The study was divided into Experiment 1 and Experiment 2. Experiment 1 involved daily administration at immunomodulating doses (2.5 mg/kg; IP) for three days, followed by a three-day break and further daily administration at immunomodulating doses (2.5 mg/kg; IP) for three days. Experiment 2 involved weekly administration at immunomodulating doses (2.5 mg/kg; IP) for four weeks. Immunomodulatory parameters, IL-5, IL-10, TNF-α, and IL-1β, were compared between free levamisole and liposomal levamisole formulations. No difference in TNF-α was found between the groups in Experiment 1 and Experiment 2. In Experiment 1, the free levamisole group showed higher values of IL-1β than did liposomal and control groups. IL-1β values in Experiment 2 were higher in the control group than in the free levamisole group. IL-5 values in Experiment 2 were higher in the control group than in the free levamisole group. In Experiment 1, IL-10 values were higher in the liposomal levamisole group and in the control group than they were in the free levamisole group. Thus it was determined that free and liposomal forms of levamisole, which have been found to have immunomodulatory effects in different animal species in many studies, also showed such effects in rats. It was concluded that studies on other animal species and other doses are needed to obtain more detailed information about the immunomodulatory effects of free and liposomal levamisole.

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The Effects of Short-Term Treatment With Levamisole on Cytokines in Volunteers and Cancer-Patients

Cited by 2 publications

References 0 publications

Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

Comparison of immunomodulatory effects of free and liposomal levamisole administered intraperitoneally to rats

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