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Immune Response Modifier (immune + response_modifier)
Selected AbstractsImmune response modifiers , mode of actionEXPERIMENTAL DERMATOLOGY, Issue 5 2006Meinhard Schiller Abstract:, The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-,B activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-,, and production of type I IFNs (IFN-, and IFN-,), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response. [source] Eruptive Epidermoid Cysts Resulting from Treatment with ImiquimodDERMATOLOGIC SURGERY, Issue 7 2005Chelsy L. Marty MD Background Because of its unique mechanism of action and safety profile, imiquimod, a topical immune response modifier, is used for many benign and malignant dermatologic conditions. Adverse effects are typically limited to treatment site erythema and erosion. Objective To describe a newly recognized adverse effect of imiquimod. Methods A 79-year-old woman being treated with imiquimod 5 days per week for a nodular basal cell developed a verrucous plaque over the treatment area after 7 weeks of therapy. Results Scouting biopsies demonstrated multiple comedones and ruptured epidermoid cysts. There was no evidence of residual basal cell carcinoma. Conclusions Imiquimod is a new and novel treatment option for cutaneous malignancies. We report its successful use in the treatment of a nodular basal cell carcinoma. The multiple comedones and ruptured epidermoid cysts are newly reported adverse effects of imiquimod therapy. [source] Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label TrialDERMATOLOGIC SURGERY, Issue 3 2005Ketty Peris MD Background Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). Objective To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. Methods Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. Results Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). Conclusions In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months. KETTY PERIS, MD, ELENA CAMPIONE, MD, TAMARA MICANTONIO, MD, GEORGIANA CLARE MARULLI, MD, MARIA CONCETTA FARGNOLI, MD, AND SERGIO CHIMENTI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] Noninvasive Imaging, Treatment, and Microscopic Confirmation of Clearance of Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 3 2003Mark Goldgeier MD BACKGROUND. The diagnosis of basal cell carcinoma (BCC) is generally established by skin biopsy followed by tissue preparation and microscopic analysis. Treatment of BCC is often accomplished by surgical excision. Objective. To confirm the presence of BCC with a noninvasive imaging technique, to treat the patient with a topical immune response modifier, and to confirm the clearance of BCC noninvasively. METHODS. Confocal microscopy (CM) is a noninvasive technique for real-time imaging of skin in vivo. Imiquimod, an immune response modifier, is applied topically by the patient to the skin lesion. RESULTS. The presence of BCC was confirmed with CM. Posttreatment CM imaging confirmed the clearance of BCC from the entire treatment field. Both the pretreatment and the posttreatment CM findings were confirmed by invasive biopsy. CONCLUSION. The ability to use CM to image in real time without discomfort to the patient makes it a powerful tool to assist in the diagnosis of skin disease. [source] Current modalities and new advances in the treatment of basal cell carcinomaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Roger I. Ceilley MD Basal cell carcinoma (BCC) is one of the most common cancers. Surgical extirpation is currently the standard of care for BCC, which is associated with several advantages and disadvantages. Procedures such as surgical excision used to treat superficial BCC (sBCC) and nodular BCC (nBCC) may have high 5-year recurrence rates if tumors are not completely excised. Curettage with electrodesiccation is a common method for treating primary BCC. However, multiple cycles are recommended and the procedure can have unsatisfactory cosmetic results (e.g. scarring and hypopigmentation). Mohs micrographic surgery has a low rate of disease recurrence but is a specialized procedure usually limited to specific indications (e.g. high-risk tumors). Cryosurgery and photodynamic therapy require multiple cycles and are associated with variable cosmetic outcomes and recurrence rates. As with any procedure, potential risks and patient quality-of-life issues need to be considered. In addition, substantial patient and healthcare provider inconvenience limit the practical utility of some modalities. Pharmacologic interventions provide another treatment option as adjunctive or monotherapy. Investigations of imiquimod, a novel immune response modifier, have indicated that this topical, noninvasive agent is safe and well tolerated and may be efficacious in the treatment of BCC. This review will highlight the role of standard treatment modalities and introduce new advances in the treatment of BCC. [source] Imiquimod 5% cream: a topical immune response modifierINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2002Mario Marini PhD No abstract is available for this article. [source] Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist imiquimodJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2005Joerg Wenzel Introduction:, Imiquimod (AldaraÔ) is an immune response modifier approved for the topical treatment of external genital and perianal warts which can mediate regression of several cutaneous malignancies [basal cell carcinoma (BCC), Bowen's disease, actinic keratosis, and metastasis of malignant melanoma]. Recently, it was discovered that imiquimod acts through the toll-like receptor (TLR) 7. We hypothesize that TLR7-signaling strongly induces the production of interferon (IFN) ,, which is able to enhance Th1-mediated cellular antiviral and antitumor immunity. Patients and methods:, In the present study we analyzed the expression of MxA, a protein specifically induced by type I IFNs during topical imiquimod treatment in several patients suffering from different cutaneous malignancies (BCC, cutaneous metastasis of melanoma, and breast cancer), and characterized the inflammatory infiltrate, along with the expression of chemokine receptor CXCR3, by immunohistochemistry. Results:, Treatment with the TLR7-agonist imiquimod induced a significant lesional lymphocytic inflammation, associated with strong expression of MxA, indicating the induction of type I IFN signaling. The extent of lesional MxA staining closely correlated with the number of infiltrating T lymphocytes and the expression of the chemokine receptor CXCR3, characteristic for Th1-biased immune responses. Discussion:, Our in vivo results suggest an important role for TLR7-induced production of type I IFN, which links innate and adaptive immunity and promotes specific Th1-biased cellular immune response capable of eliminating cutaneous malignancies. MxA appears to be a valuable parameter to demonstrate IFN-type I expression in imiquimod therapy. [source] Resolution of vulvitis circumscripta plasmacellularis with topical imiquimod: two case reportsBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2003H.L. Ee Summary Vulvitis circumscripta plasmacellularis (VCP) is a rare but well-described entity. It is notorious for its recalcitrant nature to various modalities of treatment. Intralesional interferon-, showed some promise, with complete resolution, but is coupled with the side-effect of myelosuppression. Topical imiquimod is a novel immune response modifier with the ability to induce the production of interferon-,. In this paper, we report two cases of VCP whose lesions were resistant to antibiotics, topical and oral corticosteroids, but resolved after a treatment trial with imiquimod. [source] Successful treatment of extramammary Paget's disease of the scrotum with imiquimod 5% creamCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2003B. Berman Summary Extramammary Paget's disease (EMPD) of the skin is an uncommon malignancy involving the epidermis, which sometimes extends into the dermis. Current treatments for EMPD are surgical excision, Mohs' micrographic surgery or laser ablation. We report a case of a 68-year-old male who presented with recurrent EMPD. The patient refused to have surgery and, as an alternative, he applied imiquimod 5% cream, an immune response modifier, daily for a total of 6 weeks. During the initial weeks of therapy, he experienced moderate erythema. Imiquimod treatment resulted in clinical and histological eradication of EMPD, with no recurrence observed during 6 months of follow-up. [source] Actinic keratosis treated with an immune response modifier: a case report of six patientsCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2003L. Bianchi Summary Actinic keratoses (AKs) are intraepidermal tumours, which result from the proliferation of transformed neoplastic keratinocytes. They are typically induced by chronic exposure to ultraviolet radiation, and can often develop into squamous cell carcinoma (SCC). Six patients, who presented with AKs located on the head, face and chest, were treated with the immune response modifier, imiquimod, as a 5% cream five times per week for up to 8 weeks. The majority of patients experienced mild to moderate side-effects, consisting of erythema, itching and burning. Topical application of imiquimod for 4,8 weeks resulted in complete clearance in all patients. No new or recurrent lesions were observed during a 6,8 month follow-up period. [source] Immune response modifiers , mode of actionEXPERIMENTAL DERMATOLOGY, Issue 5 2006Meinhard Schiller Abstract:, The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-,B activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-,, and production of type I IFNs (IFN-, and IFN-,), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response. [source] |