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Imiquimod

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https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#1
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
July 20, 2017: MAbs
https://www.readbyqxmd.com/read/28708859/interleukin-17a-induced-production-of-acute-serum-amyloid-a-by-keratinocytes-contributes-to-psoriasis-pathogenesis
#2
Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron
BACKGROUND: Acute-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. OBJECTIVES: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28702024/full-length-interleukin-33-aggravates-radiation-induced-skin-reaction
#3
Olga Kurow, Benjamin Frey, Louis Schuster, Verena Schmitt, Susanne Adam, Madelaine Hahn, Derek Gilchrist, Iain B McInnes, Stefan Wirtz, Udo S Gaipl, Gerhard Krönke, Georg Schett, Silke Frey, Axel J Hueber
The interleukin (IL)-1 family member IL-33 has been described as intracellular alarmin with broad roles in wound healing, skin inflammation but also autoimmunity. Its dichotomy between full length (fl) IL-33 and the mature (m) form of IL-33 and its release by necrosis is still not fully understood. Here, we compare functional consequences of both forms in the skin in vivo, and therefore generated two lines of transgenic mice which selectively overexpress mmIL-33 and flmIL-33 in basal keratinocytes. Transgene mRNA was expressed at high level in skin of both lines but not in organs due to the specific K14 promoter...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28693290/therapy-with-transcutaneous-administration-of-imiquimod-combined-with-oral-administration-of-sorafenib-suppresses-renal-cell-carcinoma-growing-in-an-orthotopic-mouse-model
#4
Takashi Karashima, Keiko Udaka, Mayumi Niimura, Katsuhide Suzuki, Hiroto Osakabe, Tsutomu Shimamoto, Satoshi Fukata, Keiji Inoue, Naoto Kuroda, Motoharu Seiki, Taro Shuin
Imiquimod is an imidazoquinoline immune response modifier that is used in antiviral and antiallergic creams. Combination therapy using transcutaneous imiquimod and oral sorafenib was previously demonstrated to reduce the tumor burden of renal cell carcinoma growing cutaneously in a mouse model. In the present study, an orthotopic mouse model was used to investigate whether combined treatment with oral sorafenib and transcutaneous imiquimod inhibited renal cell carcinoma growing in the kidney. Kidneys of female BALB/c mice were orthotopically implanted with RENCA mouse kidney cancer cells, and the mice were transcutaneously treated with cream containing imiquimod and/or with orally administered sorafenib 5 days following cell implantation...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28689773/the-toll-like-receptor-ligands-hiltonol-%C3%A2-polyiclc-and-imiquimod-effectively-activate-antigen-specific-immune-responses-in-tasmanian-devils-sarcophilus-harrisii
#5
Amanda L Patchett, Cesar Tovar, Lynn M Corcoran, A Bruce Lyons, Gregory M Woods
Devil facial tumour disease (DFTD) describes two genetically distinct transmissible tumours that pose a significant threat to the survival of the Tasmanian devil. A prophylactic vaccine could protect devils from DFTD transmission. For this vaccine to be effective, potent immune adjuvants will be required. Toll-like receptors (TLRs) promote robust immune responses in human cancer studies and are highly conserved across mammalian species. In this study, we investigated the proficiency of TLR ligands for immune activation in the Tasmanian devil using in vitro mononuclear cell stimulations and in vivo immunisation trials with a model antigen...
July 6, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28677206/imiquimod-applied-interleukin-10-deficient-mice-better-reflects-severe-and-persistent-psoriasis-with-systemic-inflammatory-state
#6
Seon-Pil Jin, Seong-Joon Koh, Da-Ae Yu, Min-Woo Kim, Hee Tae Yun, Dong Hun Lee, Hyun-Sun Yoon, Soyun Cho, Hyun-Sun Park
Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison to previous models. IL-10 deficient and wild type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15...
July 4, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28672903/efficacy-of-fulguration-combined-with-imiquimod-cream-on-condyloma-acuminatum-and-the-effect-on-immune-functions-and-serums-levels-of-il-2-and-il-10
#7
Quan Chen, Ridong Yang, Aili Gao, Daoqing Zhong, Huilan Zhu
The objective of the present study was to investigate the clinical efficacy of high-frequency fulguration combined with 5% imiquimod cream for condyloma acuminatum (CA), and the effect on T cell immune function and serum levels of interleukin (IL)-2 and IL-10. We enrolled 112 patients with CA between January 2014 and January 2016. Patients were randomly divided into the control group (n=56) and observation group (n=56). The control group received high-frequency fulguration combined with intramuscular injection of Bacillus Calmette-Guérin polysaccharide nucleic acid, and the observation group received high-frequency fulguration combined with external application of 5% imiquimod cream...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670076/acute-exacerbation-of-myasthenia-gravis-with-topical-imiquimod-use
#8
Saadeddine Saad, Bobbak Mansouri, Chad Housewright
Imiquimod activates the immune system when applied to a local area. We report a patient with a history of well-controlled myasthenia gravis who was prescribed imiquimod for lentigo maligna. Treatment was halted after 2 weeks when the patient reported itching and irritating sensations in his throat, consistent with previous myasthenia exacerbations. The symptoms improved once imiquimod use was discontinued. We advise clinicians to be cautious when prescribing imiquimod to a patient with a history of myasthenia gravis...
July 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28668835/immunomodulatory-effect-of-imiquimod-through-ccl22-produced-by-tumor-associated-macrophages-in-b16f10-melanomas
#9
Sadanori Furudate, Taku Fujimura, Yumi Kambayashi, Aya Kakizaki, Takanori Hidaka, Setsuya Aiba
BACKGROUND/AIM: Tumor-associated macrophages (TAMs), together with splenic CD11b(+) cells, help maintain the tumor microenvironment. The immunomodulatory compound imiquimod (IQM) stimulates innate immune cells, including macrophages, to induce antitumor effects. In order to elucidate the effects of IQM on the tumor microenvironment, we investigated the immunomodulatory effect of IQM during melanoma growth by using the B16F10 melanoma model. MATERIALS AND METHODS: To elucidate the immunomodulatory effects of IQM on the tumor microenvironment, we isolated CD11b(+) TAMs and splenic CD11b(+) cells and evaluated the immunomodulatory effects of IQM, using the B16F10 melanoma model...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666747/combined-immunotherapy-ctla-4-blockade-potentiates-anti-tumor-response-induced-by-transcutaneous-immunization
#10
Johanna Rausch, Pamela Aranda Lopez, Ariane Bialojan, Mark Denny, Peter Langguth, Hans Christian Probst, Hansjörg Schild, Markus P Radsak
BACKGROUND: The epidermal application of the Toll Like Receptor 7 agonist imiquimod and a T-cell peptide epitope (transcutaneous immunization, TCI) mediates systemic peptide-specific cytotoxic T-cell (CTL) responses and leads to tumor protection in a prophylactic tumor setting. However, it does not accomplish memory formation or permanent defiance of tumors in a therapeutic set-up. As a distinct immunologic approach, CTLA-4 blockade augments systemic immune responses and has shown long-lasting effects in preclinical experiments as well as in clinical trials...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28665921/rhododendrin-inhibits-toll-like-receptor-7-mediated-psoriasis-like-skin-inflammation-in-mice
#11
Yoon-Jae Jeon, Shyam Kishor Sah, Hee Seung Yang, Ji Hae Lee, Jongheon Shin, Tae-Yoon Kim
Many active compounds present in Rhododendron brachycarpum have been used in traditional Oriental medicine for the treatment of various skin diseases. However, the precise mechanism of action of the compounds isolated from R. brachycarpum and their relevance as therapeutics for the treatment of psoriasis remain elusive. In this study, we report that rhododendrin isolated from R. brachycarpum strongly inhibits imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. We showed that topical treatment with rhododendrin reduces IMQ-induced skin hyperplasia, inflammatory mononuclear cell infiltration and the expression of pro-inflammatory mediators in mouse skin...
June 30, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28661992/treatment-patterns-outcomes-and-patient-satisfaction-of-primary-epidermally-limited-nonmelanoma-skin-cancer
#12
Benjamin A Drew, Pritesh S Karia, Ariana N Mora, Christine A Liang, Chrysalyne D Schmults
BACKGROUND: Epidermally limited nonmelanoma skin cancer (ELNMSC) (superficial basal cell carcinoma [SBCC] and squamous cell carcinoma in situ [SCCIS]) is common. Data on outcomes and patient satisfaction are lacking. OBJECTIVE: To examine treatment efficacy and satisfaction in ELNMSC patients. PATIENTS AND METHODS: Retrospective cohort study of adults with primary SBCC or SCCIS. A 25% random subset completed a satisfaction questionnaire. RESULTS: Five hundred and fifty patients with 227 SBCC and 451 SCCIS were included; 329 tumors (49%) were treated with Mohs micrographic surgery (MMS) and 349 (51%) with non-MMS (imiquimod [n = 26], 5% 5-fluorouracil [n = 234], ingenol mebutate [n = 32], or cryotherapy [n = 57])...
June 28, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28658998/patient-reported-outcomes-in-topical-field-treatment-of-actinic-keratosis-in-swedish-and-danish-patients
#13
Hanna Norrlid, Jenny M Norlin, Heidi Holmstrup, Irena Malmberg, Karin Sartorius, Henrik Thormann, Gregor B E Jemec, Gunnel Ragnarson Tennvall
Topical treatments in dermatology can be long, complex and lead to nonadherence and nonpersistence to prescribed treatment. Clinical efficacy observed in randomized clinical trials (RCT) may therefore be reduced in real-world clinical practice. The objective of this study was to analyze patient-reported treatment adherence, treatment satisfaction and health-related quality of life (HRQoL) with topical treatments of actinic keratosis (AK) in routine clinical practice in Denmark and Sweden. Adult patients prescribed field-directed topical AK treatments with diclofenac gel, imiquimod or ingenol mebutate per routine clinical practice were eligible for the observational RAPID-ACT study...
June 29, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28655469/transcutaneous-immunization-with-a-novel-imiquimod-nanoemulsion-induces-superior-t-cell-responses-and-virus-protection
#14
Pamela Aranda Lopez, Mark Denny, Ann-Kathrin Hartmann, Astrid Alflen, Hans Christian Probst, Esther von Stebut, Stefan Tenzer, Hansjörg Schild, Michael Stassen, Peter Langguth, Markus P Radsak
BACKGROUND: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28652396/tlr7-signaling-regulates-th17-cells-and-autoimmunity-novel-potential-for-autoimmune-therapy
#15
Jian Ye, Yadan Wang, Xia Liu, Lingyun Li, Adeleye Opejin, Eddy C Hsueh, Huanle Luo, Tian Wang, Daniel Hawiger, Guangyong Peng
Innate regulation through TLR signaling has been shown to be important for promoting T cell subset development and function. However, limited information is known about whether differential TLR signaling can selectively inhibit Th17 and/or Th1 cells, which are important for controlling excessive inflammation and autoimmune responses. In this article, we demonstrate that activation of TLR7 signaling in T cells can inhibit Th17 cell differentiation from naive T cells and IL-17 production in established Th17 cells...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28651824/cryotherapy-to-treat-anogenital-warts-in-nonimmunocompromised-adults-systematic-review-and-meta-analysis
#16
Antoine Bertolotti, Nicolas Dupin, Fabrice Bouscarat, Brigitte Milpied, Christian Derancourt
BACKGROUND: Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations. OBJECTIVE: To compare the efficacy and safety of cryotherapy versus other AGW treatments. METHODS: Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups)...
June 23, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28647592/liposphere-mediated-topical-delivery-of-thymoquinone-in-the-treatment-of-psoriasis
#17
Anjali Jain, P Venkatesh, Upendra Bulbake, Sindhu Doppalapudi, Towseef Amin Rafeeqi, Chandraiah Godugu, Wahid Khan
Thymoquinone (TMQ) is reported with good anti-psoriatic activity; however, the hydrophobicity, poor aqueous solubility, light and pH sensitive nature of TMQ hinder its delivery to target site. To address these delivery challenges of TMQ, lipospheres were explored. The topical use of lipospheres offers an effective mean of penetration along with stability and scalability. TMQ lipospheres of particle size below 70 nm were prepared and evaluated. These lipospheres resulted in deeper skin penetration, slow release and skin compatibility...
June 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28644711/screening-for-squamous-cell-anal-cancer-in-hiv-positive-patients-a-five-year-experience
#18
Chiara Santorelli, Cosimo Alex Leo, Jonathan D Hodgkinson, Franco Baldelli, Francesco Cantarella, Emanuel Cavazzoni
AIM: Potential screening modalities for early diagnosis of squamous cell anal cancer (SCC) in HIV patients include digital anorectal examination (DARE), anal Papanicolaou testing (Pap test), human papilloma virus (HPV) co-testing, and high-resolution anoscopy. The aim of this study was to demonstrate the results of a five-year screening program for SCC in HIV patients. MATERIALS AND METHODS: We conducted a retrospective study on 204 HIV patients who underwent a screening program for SCC from October 2010 to January 2015...
June 23, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28643328/drug-repurposing-by-simulating-flow-through-protein-protein-interaction-networks
#19
M Manczinger, V Bodnár, B T Papp, B Sz Bolla, K Szabó, B Balázs, E Csányi, E Szél, G Erős, L Kemény
As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#20
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
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