Imiquimod Cream Research Articles

095 Loss of loricrin exacerbates psoriasis-like skin inflammation through altered dendritic cell homeostasis

Psoriasis is a chronic inflammatory skin disease associated with multiple predisposing factors, and one of susceptible loci known as PSORS4 is on human chromosome 1, in which epidermal differentiation complex (EDC) is located. An EDC gene loricrin (Lor) accounts for a major protein mass of cornified cell envelope (CE), the vital structure for epidermal integrity. In contrast to competent epidermal permeability barrier, Lor knockout (LKO) mice had reduced epidermal mechanical stability of the epidermis resulting from impaired cross-linking of filaggrin and keratin 1/10 in their CEs. Since mechanical stress/trauma can contribute to psoriasis induction and exacerbation, we evaluated the impact of the loss LOR in a psoriasis-like disease model. Reflecting mechanical weakness, application of mechanical stress onto the ear skin resulted in enhanced and sustained keratin 6 (K6) protein expression in LKO epidermis as determined by immunohistochemistry (IHC). LKO mice had significantly increased expression levels of cytokines that initiate psoriatic inflammatory response, including Tnf, Il1b and Ifn1a on quantitative reverse transcription PCR (RT-qPCR). Topical application of imiquimod (Aldara) cream on LKO mice resulted in a severe inflammatory phenotype; ear skin had augmented swelling, and back skin had enhanced erythema and hyperkeratosis accompanied by increased transcriptional expression levels of K6a. Since Ifn-a produced by plasmacytoid dendritic cell (pDC) is known to play a pivotal role in this model, pDC marker expression was analyzed in a steady state. Unchallenged LKO mice had significantly enhanced expression of Bst2 in the ear skin as determined by RT-qPCR and IHC. Taken together, these results indicate that reduced mechanical stability in the epidermis can exacerbate psoriasis-like skin inflammation through the alteration of DC homeostasis.

The Paget Trial: A Multicenter, Observational Cohort Intervention Study for the Clinical Efficacy, Safety, and Immunological Response of Topical 5% Imiquimod Cream for Vulvar Paget Disease.

BackgroundVulvar Paget disease is a rare skin disorder, which is most common in postmenopausal Caucasian women. They usually present with an erythematous plaque that may show fine or typical “cake icing” scaling or ulceration that may cause itching, pain, irritation, or a burning sensation. Although most cases are noninvasive, vulvar Paget disease may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The histological evidence of so-called “Paget cells” with abundant pale cytoplasm in the epithelium confirms the diagnosis. The origin of these Paget cells is still unclear. Treatment of choice is wide local excision with negative margins. Obtaining clear surgical margins is challenging and may lead to extensive and mutilating surgery. Even then, recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. A number of case reports, retrospective case series, and one observational study have shown promising results using the topical immune response modifier imiquimod.ObjectiveThis study aims to investigate the efficacy, safety, and immunological response in patients with noninvasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream.MethodsTopical 5% imiquimod cream might be an effective and safe treatment alternative for vulvar Paget disease. The Paget Trial is a multicenter observational cohort study including eight tertiary referral hospitals in the Netherlands. It is ethically approved by the Medical-Ethical Committee of Arnhem-Nijmegen and registered in the Central Committee on Research Involving Human Subjects (CCMO) Register by as NL51648.091.14. Twenty patients with (recurrent) noninvasive vulvar Paget disease will be treated with topical 5% imiquimod cream three times a week for 16 weeks. The primary efficacy outcome is the reduction in lesion size at 12 weeks after end of treatment. Secondary outcomes are safety, immunological response, and quality of life. Safety will be assessed by evaluation of adverse events and tolerability of treatment. To evaluate the immunological response, various immunological markers will be tested on biopsy specimens taken before, during, and after treatment. Quality of life will be assessed with three questionnaires taken before, during, and after treatment.ResultsFirst results are expected in the summer of 2018.Trial RegistrationClinicalTrials.gov NCT02385188; https://clinicaltrials.gov/ct2/show/NCT02385188 (Archived by WebCite at http://www.webcitation.org/6sXygHuhP).

Long-Term Outcomes of Melanoma In Situ Treated With Topical 5% Imiquimod Cream: A Retrospective Review.

Melanoma in situ (MIS) is a noninvasive form of melanoma for which nonsurgical therapeutic options continue to be explored. The off-label use of topical 5% imiquimod cream in the management of MIS has shown potential but reported recurrence rates vary considerably between 0% and 40%. Furthermore, the long-term efficacy of imiquimod is not well established. To determine the recurrence rate of MIS among patients treated with topical 5% imiquimod cream at Dartmouth-Hitchcock Medical Center with at least 1 year of follow-up. A retrospective chart review identified 12 patients with MIS who have been treated with topical 5% imiquimod cream for 6 to 12 weeks. Patients who underwent surgical treatment for MIS were excluded from analysis. Of 12 patients with histologically confirmed MIS treated with topical 5% imiquimod cream, there were 2 recurrences (17%) during a median follow-up time of 5.5 years. Although surgery is still considered the gold standard for the treatment of MIS, imiquimod may represent a potentially effective noninvasive treatment option for patient who are not surgical candidates.

Genital Bowen's Disease in a Bulgarian Patient: Complete Remission after Surgical Approach.

A 60-year-old male patient presented with complaints of persistent red to a brown-colored plaque on his scrotum, with duration of approximately three years. The patient had been treated with oral and topical antifungals for inguinal tinea for several months and after that with topical corticosteroids for eczema for several more months. None of the regimens achieved any therapeutic effect. The histopathological evaluation revealed the presence of atypical keratinocytes in all layers of the epidermis with the altered epidermal pattern, spread parabasal mitotic activity, without secondary satellites, multiple dyskeratotic cells and multinucleated cells. The diagnosis of an intraepithelial non-invasive squamous cell carcinoma, associated with koilocytic dysplasia and hyperplasia was made, meeting the criteria for Bowen disease. An elliptic surgical excision of the lesion was made, while the defect was closed with single stitches, with excellent therapeutic and aesthetic result. First described by John T. Bowen in 1912, Bowen disease (BD) represents a squamous cell carcinoma (SCC) in situ with the potential for significant lateral spread. Treatment options include the application of topical 5-flurorouracil cream – useful in non-hairy areas, imiquimod cream or destructive methods such as radiation, curettage, cryotherapy, laser ablation and photodynamic therapy, especially useful in nail bed involvement. Despite the early lesions, surgical excision is the preferred treatment option, regarding the potential malignant transformation risk.

Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis

BackgroundAcute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines.ObjectivesWe investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients.MethodsNHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay.ResultsIL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed.ConclusionKeratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.

Anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patient: a systematic review and meta-analysis of the efficacy and safety of interventions assessed in controlled clinical trials

ObjectivesAnogenital warts (AGW, condylomata acuminata) and intraepithelial neoplasia (IEN) do not only impact health and social well-being, they are also associated with considerable costs for the healthcare systems. Immunocompromised and...

Effects of interleukin-36α on psoriasiform skin lesions and C-C motif chemokine ligand 20 expression in mice

Objective To evaluate effects of interleukin-36α (IL-36α) on psoriasiform skin lesions and C-C motif chemokine ligand 20 (CCL20) expression in mice. Methods Totally, 30 BALB/c female mice were randomly and equally divided into 3 groups: control group treated with topical vaseline cream on the shaved back and intracutaneous injection with phosphate buffer saline (PBS) , model group treated with topical imiquimod cream on the shaved back and intracutaneous injection with PBS, experimental group treated with topical imiquimod cream on the shaved back and intracutaneous injection with IL-36α solution. Psoriasis area severity index (PASI) was used to evaluate changes of psoriasiform skin lesions in mice, and light microscopy to observe morphological changes of skin lesions and to measure the thickness of the epidermis. Real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the expression of IL-36α in skin lesions in the control group and model group, and qRT-PCR, Western blot analysis and immunohistochemical study to evaluate changes of CCL20 levels in skin lesions. Results The model group showed significantly increased mRNA (∆Ct value: 0.0195 ± 0.0059) and protein expression (3.922 ± 0.248) of IL-36α compared with the control group (mRNA: 0.0012 ± 0.0004, P < 0.05; protein: 0.690 ± 0.025, P < 0.05) . The mRNA and protein expression of CCL20 were significantly higher in the experimental group than those in the model group (mRNA: 2.152 ± 0.793 vs. 0.999 ± 0.178; protein: 0.397 ± 0.033 vs. 0.145 ± 0.030; both P < 0.05) , and higher in the model group than those in the control group (mRNA: 0.378 ± 0.075; protein: 0.025 ± 0.009; both P < 0.05) . Immunohistochemical study showed that the expression intensity of CCL20 in skin lesions significantly increased in the experimental group compared with that in the model group (Z= 2.294, P < 0.05) . Conclusion IL-36α may aggravate psoriasiform skin inflammation in mice by promoting CCL20 expression. Key words: Psoriasis; Disease models, animal; Chemokine CCL20; Imiguimod; Interleukin-36α

Combinational effects of maxacalcitol and betamethasone butyrate propionate on imiquimod-induced psoriasis-like dermatitis in mice

Psoriasis is a chronic inflammatory skin disease, characterized by epidermal hyper-proliferation, abnormal differentiation and inflammatory cell infiltration. The combination therapy of vitamin D3 analogue (VD3) and glucocorticoid has been widely used for the topical treatment of psoriasis because of its better efficacy compared to each monotherapy. However, their underlying mechanisms on the combinational effects have not yet been fully elucidated. Therefore, we investigated the comparative effects of a novel VD3/glucocorticoid combination product, which contains maxacalcitol (MCT) and betamethasone butyrate propionate (BBP), with MCT or BBP single product on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Mice were treated topically with IMQ cream for 4 consecutive days, and drugs were topically administrated for 3 days from the next day of the first IMQ treatment. MCT/BBP combination product strongly ameliorated the development of IMQ-induced psoriasis-like skin lesions. Histological findings also showed that it suppressed the thickening of epidermis and inflammatory cell infiltration in dermis. Moreover, it reduced an elevation in mRNA levels of Th17 cytokines (IL-17A, IL-17F, IL-22), inflammatory cytokines (TNF-α, IL-1β) and an antimicrobial peptide (S100A7), and increased those of epidermal differentiation markers (K1, Filaggrin, Loricrin) in dorsal skin. These effects were much stronger than the single products. In conclusion, our results demonstrated the remarkable improvement effect of MCT/BBP combination product to abnormal immune reaction and epidermal dysfunction, supporting the superior clinical efficacy of combination therapy compared to monotherapy in psoriasis.

GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression.

BackgroundProphylactic vaccines are available for women and girls not yet infected with HPV, but women already infected with HPV need a treatment to prevent progression to high-grade cervical lesions and cancer. GTL001 is a bivalent therapeutic vaccine for eradicating HPV-infected cells that contains HPV16 E7 and HPV18 E7 both fused to detoxified adenylate cyclase from Bordetella pertussis, which binds specifically to CD11b+ antigen-presenting cells. This study examined the ability of therapeutic vaccination with GTL001 adjuvanted with topical imiquimod cream to induce functional HPV16 E7- and HPV18 E7-specific CD8+ T cell responses.MethodsBinding of GTL001 to human CD11b was assessed by a cell-based competition binding assay. Cellular immunogenicity of intradermal vaccination with GTL001 was assessed in C57BL/6 mice by enzyme-linked immunospot assay and in vivo killing assays. In vivo efficacy of GTL001 vaccination was investigated in the TC-1 murine HPV16 E7-expressing tumor model.ResultsGTL001 bound specifically to the human CD11b/CD18 receptor. GTL001 adjuvanted with topical 5% imiquimod cream induced HPV16 E7 and HPV18 E7-specific CD8+ T cell responses. This CD8+ T-cell response mediated in vivo killing of HPV E7-expressing cells. In the HPV16 E7-expressing tumor model, GTL001 adjuvanted with imiquimod but not imiquimod alone or a combination of unconjugated HPV16 E7 and HPV18 E7 caused complete tumor regression.ConclusionsGTL001 adjuvanted with topical 5% imiquimod is immunogenic and induces HPV16 E7 and HPV18 E7-specific CD8+ T cell responses that can kill HPV E7-expressing cells and eliminate HPV E7-expressing tumors.

Treatment of Porokeratosis: A Systematic Review.

Porokeratosis (PK) is a rare skin disease of unknown etiology. It consists of a keratinization disorder, which may appear in several clinical forms and can undergo malignant transformation. The histopathological hallmark of PK is the cornoid lamella. While many topical, systemic, and surgical treatment modalities for PK have been described, no randomized controlled trials have been performed yet. Because of a lack of treatment standards for PK, European and international guidelines cannot be created. The aim of this systematic review is to outline options for treating PK. We performed a systematic literature search in an electronic database for published literature. A total of 88 articles fulfilling our inclusion criteria were found. There were no randomized controlled trials on the treatment of PK, but mainly case reports and case series. Porokeratosis of Mibelli showed the best outcomes after treatment with imiquimod cream and linear PK responded well to topical or systemic retinoids. Topical vitamin D acid derivatives may be the best therapeutic option for disseminated PK. Surgical interventions and cryotherapy may be preferred in areas where the use of topical agents is difficult or contraindicated. To offer patients with PK an evidence-based high-quality standardized therapy, randomized controlled trials are needed.

Erythroplasia of Queyrat Treated with 5% Imiquimod Cream — Case Report Emphasizing the Role of Human Papilloma Virus Testing in a Clinical Setting

AbstractBackground:Anogenital premalignancies and malignancies often affect females and males, and human papillomavirus infection plays a crucial role in their etiopathogenesis. These lesions are very important and represent an immense public health burden.Case presentation:A 78-year-old Caucasian male presented to the Dermatology Unit for persistent, slowly progressing, well-demarcated, erythematous plaques on the glans penis, observed by the patient 18 months prior to the consultation. Variable topical treatments were applied, with no improvement and with the denial of a punch biopsy. A clinical diagnosis of erythroplasia of Queyrat was established and the test for HPV revealed an association with subtype 16 (which excluded other benign inflammatory conditions). Positive results were obtained after 4 weeks of topical application of 5% imiquimod cream, once daily, 5 times a week.Conclusion:Erythroplasia of Queyrat should be diagnosed in a non-compliant patient based on the clinical picture and HPV testing even in the absence of a biopsy, and a non-surgical treatment should be initiated immediately.

BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis.

BAY 11-7082 antagonizes I-κB kinase-β preventing nuclear translocation of nuclear factor-κB (NF-κB); it also inhibits NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation. NF-κB is involved in psoriasis, whereas the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod (IMQ) cream (62.5mg/day) on the shaved back skin of C57BL/6 and NLRP3 knockout (KO) mice for 7 consecutive days. Sham psoriasis animals were challenged with Vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20mg/kg/i.p.) or its vehicle (100μl/i.p of 0.9% NaCl). Skin of IMQ animals developed erythema, scales, thickening and epidermal acanthosis. IMQ skin samples showed increased expression of pNF-κB and NLRP3 activation. BAY 11-7082 blunted epidermal thickness, acanthosis and inflammatory infiltrate. BAY 11-7082 reduced pNF-κB, NLRP3, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β expression, blunted the phosphorylation of signal transducer and activators of transcription 3 (STAT3) and decreased IL-23 levels. In addition, BAY 11-7082 reawakened the apoptotic machinery. NLRP3 KO animals showed a reduced total histological score but persistent mild acanthosis, dermal thickness and expression of pNF-κB and pSTAT3, following IMQ application. Our data suggest that BAY 11-7082 might represent an interesting approach for the management of psoriasis-like dermatitis depending on the dual inhibition of NF-κB and NLRP3.

GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory T-cell responses that inhibit tumor growth

GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8+ T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8+ T-cell responses to both vaccine antigens. Intradermal vaccination of C57BL/6 mice with GTL001 adjuvanted with a TLR3 agonist (polyinosinic-polycytidylic acid) or a TLR7 agonist (topical 5% imiquimod cream) induced strong HPV16 E7-specific T-cell responses capable of eradicating HPV16 E7-expressing tumors. Tumor-free mice also had antigen-specific memory T-cell responses that protected them against a subsequent challenge with HPV18 E7-expressing tumor cells. In addition, vaccination with bivalent vaccines containing CyaA-HPV16 E7 and CyaA fused to a tumor-associated antigen (melanoma-specific antigen A3, MAGEA3) or to a non-viral, non-tumor antigen (ovalbumin) eradicated HPV16 E7-expressing tumors and protected against a later challenge with MAGEA3- and ovalbumin-expressing tumor cells, respectively. These results show that CyaA-based bivalent vaccines such as GTL001 can induce both therapeutic and prophylactic anti-tumor T-cell responses. The CyaA platform can be adapted to different antigens and adjuvants, and therefore may be useful for developing other therapeutic vaccines.

Topical imiquimod 5% as an alternative therapy in periocular basal cell carcinoma in two patients with surgical contraindication

Abstract Clinical cases The cases are presented of two patients with periocular basal cell carcinoma of the eyelid who received topical imiquimod 5%, with a good response. Both had a functional state that contraindicated surgical treatment. Conclusion Imiquimod cream 5% was shown to be an effective alternative to surgical treatment of periocular basal cell carcinoma, especially in those cases where surgery is not possible.

Treatment of Cervical Intraepithelial Neoplasia: Patients Preferences for Surgery or Immunotherapy with Imiquimod

Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differed for the imiquimod alternatives. Women assigned a positive utility to LLETZ compared with imiquimod. When making a choice for imiquimod, women preferred a higher treatment success rate and a lower risk of premature birth, infertility and side effects. The choice for imiquimod treatment was also influenced by the intention of a future pregnancy. Subgroup analyses revealed that a lower efficacy regarding imiquimod might be more acceptable for women who desired a future pregnancy compared with women who did not desire a future pregnancy. Women with a future pregnancy wish may prefer treatment of high-grade CIN with imiquimod cream over LLETZ, if the risk of subfertility and premature birth is low.

Imiquimod 5% cream for the treatment of large nodular basal cell carcinoma at the medial canthal area

Context (Background):Imiquimod (IMQ) 5% cream is an immunomodulatory and antitumorigenic agent, which was used as a topical treatment regimen, who had periocular basal cell carcinoma (BCC).Aim:This study aims to present three cases with large BCC at the medial canthal area treated with IMQ 5% cream.Materials and Methods:IMQ 5% cream was used in three patients with ages 45, 49, and 73 who preferred medical treatment over surgery. Following incisional biopsy IMQ cream was used once a day, 5 times a week and the patients were followed up weekly during 12 week treatment period and monthly after the clearance of the lesion.Results:Erythema and erosion on the surface of the lesion, injection of conjunctiva, burning and itching sensation, epiphora and punctate keratitis were seen in all patients during the treatment period. The ophthalmic side effects could be managed by topical lubricating eye drops and the inflammatory reactions resolved within 1 month after cessation of therapy. The patients were followed up for at least 3 years without tumor recurrence and the biopsies taken from the suspected area were found to be tumor free.Conclusion:Surgical excision of carcinoma of the eyelid at medial canthal area can be difficult without causing damage to the lacrimal system and reconstruction of the defect may need grafts or flaps. IMQ may provide an alternative therapy to surgery in certain cases.

Fractional Laser-Assisted Topical Imiquimod 5% Cream Treatment for Recalcitrant Common Warts in Children: A Pilot Study.

Conventional treatments for warts like cryotherapy are limited by the pain during procedures, especially in pediatric patients. Imiquimod is a topical immune response modifier, but the thick stratum corneum of common warts prevents drug permeation through skin. To evaluate the efficacy and safety of fractional laser/topical 5% imiquimod cream for the treatment of warts in children. Eleven pediatric patients with multiple recalcitrant common warts were included. Lesions were treated using an ablative fractional 2,940-nm Er:YAG laser at 1- or 2-week interval. After each laser treatment session, imiquimod 5% cream was self-applied once daily 5 days a week. Response and adverse effects were assessed 2 weekly until complete clearance or up to maximum of 48 weeks. Pain during fractional laser was assessed using a visual analogue scale (0-10). Eight of the 11 (72.7%) children experienced complete clearance. Mean duration was 29.7 (16-48) weeks, and the mean number of fractional laser was 17.5 (8-37). No significant adverse effect was observed. Pain visual analogue scale during fractional laser was 2.4 (1-4) compared to 6.2 (5-8) during cryotherapy. This pilot study indicates that fractional laser-assisted topical imiquimod may provide benefit for recalcitrant warts in children.

Kinetic of two distinct diseases induced by topical treatment with imiquimod cream in mice: Skin inflammation and systemic autoimmunity

It has been widely recognized that topical treatment of mice with imiquimod (IMQ) cream results in generation of skin inflammation, which resembles human psoriasis. We previously reported that topical treatment with TLR7 agonists including IMQ and resiquimod also induced lupus-like systemic autoimmunity in wild-type mice. Thus, although IMQ treatment induces two distinct diseases, it remains unknown whether the underlying pathomechanism is common between them. In this study, we explored detailed kinetics of development of both diseases.

Immunomodulatory effects of imiquimod cream on tumor-infiltrating leukocytes in B16F10 melanomas

Immunomodulatory effects of imiquimod cream on tumor-infiltrating leukocytes in B16F10 melanomas

Antineoplastic effect of laser immunotherapy in mice with multiple cutaneous squamous cell carcinoma

Objective To evaluate the antineoplastic effect of laser immunotherapy in mice with multiple cutaneous squamous cell carcinoma (CSCC) . Methods Normal immunocompetent hairless SKH-1 mice were consecutively irradiated by ultraviolet rays to establish mouse models of multiple CSCC. Then, 20 CSCC-bearing mice were randomly and equally divided into 4 groups: laser group irradiated with an 808-nm near-infrared laser (1 W/cm2, 10 minutes) once every two weeks for a total of 3 sessions, laser immunotherapy group irradiated with an 808-nm near-infrared laser as above and topically treated with imiquimod cream once a day for 3 days before and after each session of irradiation, imiquimod group treated with imiquimod cream as in the laser immunotherapy group, and control group receiving no treatment. The volume of tumors was calculated, and their morphology as well as the survival of mice were observed after the treatment. The t test and Mantel-Cox log-rank test were used to compare the volume of tumors on the dorsum and survival rates of mice, respectively, on days 27 and 60 after the start of treatment. Another 12 CSCC-bearing mice were randomly and equally divided into the 4 groups mentioned above, and tumor tissues were resected from these mice for histopathological examination on day 5 after the first treatment. Results On day 27, the volume of tumors significantly increased in the control group and imiquimod group (both P 0.05) . Moreover, the volume of tumors in the control group was slightly larger than that in the imiquimod group (P > 0.05) , but significantly larger than that in the laser group and laser immunotherapy group (both P 0.05) , significantly longer in the laser group and laser immunotherapy group compared with the control group (both P 0.05) . Histopathological examination showed that 5-day topical application of imiquimod cream did not cause death of tumor cells, but numerous tumor cells died in the laser group and laser immunotherapy group. Multiple inflammatory cells were observed around the tumors, and the number of the inflammatory cells was obviously larger in both the laser group and laser immunotherapy group, especially in the latter group, compared with the control group. Conclusion Laser immunotherapy is a new effective and safe treatment for CSCC in mice, and has potential value especially in the treatment of multiple or metastatic CSCC. Key words: Neoplasms, squamous cell; Laser; Immunity; Mice