Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod

Rocco, Rodrigo; Alegre, Nadia Soledad; Pozner, Raúl; Wainstok, Rosa; Gazzaniga, Silvina

doi:10.1016/j.toxlet.2018.01.016

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…Since we have detected a different response to a vasoconstriction stimulus, we can speculate that the application of topical IMI may act also at a vascular level. Accordingly, a few recent studies have highlighted an antiangiogenic effect of topical IMI, thus suggesting a possible use in the treatment of hemangiomas [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy

et al. 2020

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Background and objectives: The possible evolution of actinic keratoses (AKs) into invasive squamous cell carcinomas (SCC) makes their treatment and monitoring essential. AKs are typically monitored before and after treatment only through a visual analysis, lacking a quantitative measure to determine treatment effectiveness. Near-infrared spectroscopy (NIRS) is a non-invasive measure of the relative change of oxy-hemoglobin and deoxy-hemoglobin (O2Hb and HHb) in tissues. The aim of our study is to determine if a time and frequency analysis of the NIRS signals acquired from the skin lesion before and after a topical treatment can highlight quantitative differences between the AK skin lesion area. Materials and Methods: The NIRS signals were acquired from the skin lesions of twenty-two patients, with the same acquisition protocol: baseline signals, application of an ice pack near the lesion, removal of ice pack and acquisition of vascular recovery. We calculated 18 features from the NIRS signals, and we applied multivariate analysis of variance (MANOVA) to compare differences between the NIRS signals acquired before and after the therapy. Results: The MANOVA showed that the features computed on the NIRS signals before and after treatment could be considered as two statistically separate groups, after the ice pack removal. Conclusions: Overall, the NIRS technique with the cold stimulation may be useful to support non-invasive and quantitative lesion analysis and regression after a treatment. The results provide a baseline from which to further study skin lesions and the effects of various treatments.

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Section: Discussionmentioning

confidence: 99%

Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy

et al. 2020

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“…It is well characterized that IQ binding to TLR7/8 initiates the receptor signalling pathway that could stimulate cytokine production through activation of the transcription factor NF‐κB 1 . To investigate whether the selective cytotoxicity on transformed and normal EC 12 was due to differential levels of TLR 7/8, we measured their expression by RT‐qPCR. TLR7 levels resulted extremely low in the H5V and 1G11 cell lines compared with the expression in lymph node cells, while the expression of TLR8 was undetectable in these EC lines (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Cells were treated with IQ (0–50 μg/mL) for 2, 4, 12 and 24 h. When indicated, N‐acetylcysteine (NAC) (10 mM) was used as an antioxidant and BAY 11–7082 (10 μM) was used to inhibit the NF‐κB signalling pathway. Cell viability was assayed by staining adherent cells with crystal violet dye 12 . Nuclear morphometric analysis (NMA) was performed to quantify apoptotic, senescent and normal nuclei in cells stained with 10 μg/mL Höechst 33458 12,27 .…”

Section: Experimental Designmentioning

confidence: 99%

“…Interestingly, in the absence of immune cells, i.e. through a direct mechanism, IQ selectively produced more apoptosis, migration impairment and cytoskeleton disorders in transformed than normal EC 12 . Although various actors of this direct mechanism have been described, the whole mechanism is far from being fully characterized 13–19 .…”

Section: Introductionmentioning

confidence: 99%

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Early redox homeostasis disruption contributes to the differential cytotoxicity of imiquimod on transformed and normal endothelial cells

Rocco

Botto

Muñoz

et al. 2021

Experimental Dermatology

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The off-label use of imiquimod (IQ) for hemangioma treatment has shown clinical benefits. We have previously reported a selective direct IQ-cytotoxic effect on transformed (H5V) vs. normal (1G11) endothelial cells (EC). In the present study, we investigated the mechanism underlying this selective cytotoxicity in terms of TLR7/8 receptor expression, NF-κB signalling and time-dependent modifications of oxidative stress parameters (ROS: reactive oxygen species, catalase and superoxide dismutase activities, GSH/GSSG and lipid peroxidation). TLR7/8 level was extremely low in both cell lines, and IQ did not upregulate TLR7/8 expression or activate NF-κB signalling. IQ significantly induced ROS in H5V after 2 h and strongly affected antioxidant defenses.After 12 h, enzyme activities were restored to baseline levels but a robust drop in GSH/GSSG persisted together with increased lipid peroxidation levels and a marked mitochondrial dysfunction. Although in normal IQ-treated EC some oxidative stress parameters were affected after 4 h, mitochondrial health and GSH/GSSG ratio remained notably unaffected after 12 h. Therefore, the early alterations (0-2 h) in transformed EC breached redox homeostasis as strongly as to enhance their susceptibility to IQ. This interesting facet of IQ as redox disruptor could broaden its therapeutic potential for other skin malignancies, alone or in adjuvant schemes.

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“…Before the initiation of β blockers for IH treatment, 5% imiquimod cream was used for the treatment of superficial IH and achieved good therapeutic outcomes (96)(97)(98). Studies (99,100) have shown that after imiquimod treatment, the cell proliferation of hemangioma decreased and apoptosis increased, the expression of TIMP-1 increased, and the expression of MMP-9 decreased. With the use of imiquimod in clinical practice, severe local irritation such as erythema and even scar formation may occur (101).…”

Section: Imiquimodmentioning

confidence: 99%

Progress in the treatment of infantile hemangioma

et al. 2019

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Infantile hemangioma (IH) is a common benign tumor, which mostly resolves spontaneously; however, children with high-risk IH need treatment. Currently, the recognized first-line treatment regimen for IH is oral propranolol, but research on the pathogenesis of IH has led to the identification of new therapeutic targets, which have shown good curative effects, providing more options for disease treatment.This article summarizes the applications of different medications, dosages, and routes of administration for the treatment of IH. In addition to drug therapy, this article also reviews current therapeutic options for IH such as laser therapy, surgical treatment, and observation. To provide the best treatment, therapeutic regimens for IH should be selected based on the child's age, the size and location of the lesion, the presence of complications, the implementation conditions, and the potential outcomes of the treatment.

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Selective hemangioma cell dysfunction and apoptosis triggered by in vitro treatment with imiquimod

Cited by 8 publications

References 39 publications

Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy

Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy

Early redox homeostasis disruption contributes to the differential cytotoxicity of imiquimod on transformed and normal endothelial cells

Progress in the treatment of infantile hemangioma

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