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Topical application of imiquimod as a treatment for chromoblastomycosis.

ABSTRACT: Chromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topical applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral antifungal therapy.

SUBMITTER: de Sousa Mda G

PROVIDER: S-EPMC4036686 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Topical application of imiquimod as a treatment for chromoblastomycosis.

de Sousa Maria da Glória Teixeira Mda G Belda Walter W Spina Ricardo R Lota Priscila Ramos PR Valente Neusa Sakai NS Brown Gordon D GD Criado Paulo Ricardo PR Benard Gil G

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20140314 12

Chromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topical applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral ant ...[more]

PMID: 24633683

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Vaccination and topical imiquimod treatment promote immune signatures in melanoma

Project description:Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.

2017-04-01 | GSE80028 | GEO

Topical application of endothelin receptor a antagonist attenuates imiquimod-induced psoriasiform skin inflammation.

Project description:Endothelin-1 (ET-1) is well known as the most potent vasoconstrictor, and can evoke histamine-independent pruritus. Recently, its involvement in cutaneous inflammation has begun to draw attention. The upregulation of ET-1 expression in the epidermis of human psoriasis patients has been reported. It was also demonstrated that ET-1 can stimulate dendritic cells to induce Th17/1 immune responses. However, the role of the interaction between ET-1 and ET-1 receptors in the pathogenesis of psoriasis remains elusive. Here, we investigated the effects of ET-1 receptor antagonist on imiquimod (IMQ) -induced psoriasiform dermatitis in mouse. Psoriasis-related cytokines such as IL-17A and TNF-α induced ET-1 expression in human keratinocytes. Topical application of selective endothelin A receptor (ETAR) antagonist ambrisentan significantly attenuated the development of IMQ-induced psoriasiform dermatitis and also significantly inhibited the histological inflammation and cytokine expression (TNF-α, IL-12p40, IL-12 p19, and IL-17) in the lesional skin of the mouse model. Furthermore, topical application of ambrisentan suppressed phenotypic and functional activation of dendritic cells in lymph nodes. Our findings indicate that the ET-1 and ETAR axis plays an important role in the pathogenesis of psoriasis and is a potential therapeutic target for treating psoriasis.

| S-EPMC7289852 | biostudies-literature

Safety, efficacy, and patient acceptability of imiquimod for topical treatment of actinic keratoses.

Project description:Imiquimod, an immune-modulating imidazoquinoline compound, has been approved in topical formulation for the treatment of actinic keratoses, superficial basal cell carcinomas, and external genital warts. Its use in the treatment of field cancerization, in particular, has been rapidly evolving. With the recent approval of a new drug application for a new concentration, as well as generic formulations, this drug has emerged at the forefront of treatment for actinic keratoses, with improved dosage scheduling and more patients having access to generic options. In the nearly 15 years since its original approval by the Food and Drug Administration for the treatment of actinic keratoses in 1997, topical imiquimod has been reviewed and studied extensively, not only for its safety and efficacy, but also for its tolerability in patients. This paper provides an indepth review of the literature, and provides clinical evidence for its inclusion in the arsenal of treatment options for patients with actinic keratoses.

| S-EPMC3114604 | biostudies-other

Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream.

Project description:BackgroundThe objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling.MethodsA double-blind, placebo-controlled, randomized study was conducted to evaluate gene expression changes in actinic keratosis treated with imiquimod 5% cream. Male subjects (N = 17) with > or = 5 actinic keratosis on the scalp applied placebo cream or imiquimod 3 times a week on nonconsecutive days for 4 weeks. To elucidate the molecular processes involved in actinic keratosis lesion regression by imiquimod, gene expression analysis using oligonucleotide arrays and real time reverse transcriptase polymerase chain reaction were performed on shave biopsies of lesions taken before and after treatment.ResultsImiquimod modulated the expression of a large number of genes important in both the innate and adaptive immune response, including increased expression of interferon-inducible genes with known antiviral, anti-proliferative and immune modulatory activity, as well as various Toll-like receptors. In addition, imiquimod increased the expression of genes associated with activation of macrophages, dendritic cells, cytotoxic T cells, and natural killer cells, as well as activation of apoptotic pathways.ConclusionData suggest that topical application of imiquimod stimulates cells in the skin to secrete cytokines and chemokines that lead to inflammatory cell influx into the lesions and subsequent apoptotic and immune cell-mediated destruction of lesions.

| S-EPMC1796543 | biostudies-literature

Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

Project description:The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

| S-EPMC5297094 | biostudies-literature

A case report of imiquimod topical therapy as treatment for cutaneous metastasis of breast cancer.

Project description:Cutaneous metastasis of breast cancer carries a poor prognosis, invokes a poor quality of life, and increases mortality by raising one's risk of bleeding and infection. Currently, options for treatment are systemic chemotherapy, surgical resection and radiation. These treatments are invasive and can have toxic side effects. A 50-year-old African-American woman with stage IV breast cancer with cutaneous metastasis to the left anterior chest and left supraclavicular area was successfully treated with topical imiquimod. She experienced improvement in appearance and symptoms within several months of starting treatment, resulting in near resolution of her cutaneous metastasis. Imiquimod is currently approved for several cutaneous conditions and has the potential to treat cutaneous metastasis of breast cancer.

| S-EPMC8239964 | biostudies-literature

Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect.

Project description:The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers.

| S-EPMC8391905 | biostudies-literature

Topical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasia (TOPIC-3): A Nonrandomized Multicenter Study.

Project description:Topical imiquimod could be an alternative, noninvasive, treatment modality for high-grade cervical intraepithelial neoplasia (CIN). However, evidence is limited, and there are no studies that compared treatment effectiveness and side effects of topical imiquimod cream to standard large loop excision of the transformation zone (LLETZ) treatment. A multi-center, nonrandomized controlled trial was performed among women with a histologic diagnosis of CIN 2/3. Women were treated with either vaginal imiquimod (6.25 mg 3 times weekly for 8 to 16 wk) or LLETZ according to their own preference. Successful treatment was defined as the absence of high-grade dysplasia at the first follow-up interval after treatment (at 20 wk for the imiquimod group and at 26 wk for the LLETZ group). Secondary outcome measures were high-risk human papillomavirus (hrHPV) clearance, side effects, and predictive factors for successful imiquimod treatment. Imiquimod treatment was successful in 60% of women who completed imiquimod treatment and 95% of women treated with LLETZ. hrHPV clearance occurred in 69% and 67% in the imiquimod group and LLETZ group, respectively. This study provides further evidence on topical imiquimod cream as a feasible and safe treatment modality for high-grade CIN. Although the effectiveness is considerably lower than LLETZ treatment, imiquimod treatment could prevent initial surgical treatment in over 40% of women and should be offered to a selected population of women who wish to avoid (repeated) surgical treatment of high-grade CIN.

| S-EPMC8906243 | biostudies-literature

A pilot study of topical imiquimod therapy for the treatment of recurrent extramammary Paget's disease.

Project description:ObjectiveThe objective of this prospective pilot study was to assess the clinical and histologic effects of topical imiquimod therapy on recurrent extramammary Paget's disease of the vulva.MethodsPatients with biopsy-proven recurrent extramammary Paget's disease presenting to the gynecology outpatient services at two participating institutions were recruited for conservative treatment with 5% imiquimod cream from 2007 to 2011. The topical cream was to be applied 3 times per week for 12weeks. Punch biopsy and photography were performed at baseline and at the 12-week time point.ResultsEight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy.ConclusionTopical 5% imiquimod cream is a safe and feasible option for women suffering from recurrent extramammary Paget's disease of the vulva, and should be considered as a viable alternative to surgical management. Given the rare nature of this disease, additional multi-institutional prospective studies should be conducted to explore the efficacy of this treatment regime.

| S-EPMC4917425 | biostudies-literature

Topical imiquimod yields systemic effects due to unintended oral uptake.

Project description:Repetitive application of topical imiquimod is used as an experimental model for the induction of psoriasiform skin lesions in mice. The model is characterized by several inflammatory processes, including cytokine production both locally and systemically, cellular infiltration, and splenomegaly. To investigate the production of type I interferons in response to imiquimod-containing Aldara cream, IFNβ-luciferase reporter mice were imaged in vivo and ex vivo. Type I interferons were found to be produced in the skin, but also in the intestinal system caused by unintended ingestion of imiquimod by the mice. Through the use of Elizabethan collars to prevent ingestion, these effects, including psoriasiform lesions were nearly completely prevented. Our findings reveal that topical treatment with Aldara induces a psoriasiform skin inflammation, but that its mode of action depends on ingestion of the chemical, which leads to systemic responses and affects local inflammation. Therefore, potential ingestion of topical treatments during experimental procedures should be taken into account during assessment of cutaneous inflammatory parameters in skin disease models.

| S-EPMC4730190 | biostudies-other

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