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Keratinocytes are immunocompetent cells important for the structural and barrier function of skin. Psoriatic keratinocytes are characterized by the enhanced proliferation and reduced differentiation rates as well as by the elevated production of proinflammatory cytokines and chemoattractants. In this research we have knocked-down a scaffold protein IQGAP3 using shRNA in HaCaT keratinocytes (HaCaT_shIQ3) in order to test the hypothesis if IQGAP3 mediates the psoriatic phenotype of keratinocytes. IQGAP interacts with cell adhesion molecules, with the cytoskeleton, with signaling molecules to regulate cell morphology, motility and kinase pathways.
Aberrant Hedgehog (Hh) signaling drives the development of basal cell carcinomas (BCCs), which arise mainly in elderly patients. Loss-of-function PTCH1 or gain-of-function SMO mutations are oncogenic drivers in human BCC, but neither of these genetic alterations effectively yield nodular BCCs in genetically-engineered mice. Because nearly all prior BCC modeling studies have been performed in juvenile mice, we set out to assess whether aging is permissive for BCC development using a Cre-inducible oncogenic SmoM2 allele, activated in skin of young versus aged mice.
Objectives: Two pivotal Phase III randomized, double-blinded, vehicle-controlled, studies (KX01-AK-003/KX01-AK-004) evaluated the efficacy and safety of tirbanibulin ointment 1% vs. vehicle in adults with AK on the face/scalp. Methods: Eligible subjects with 4-8 clinically visible AK lesions in a 25 cm2 area were randomized 1:1 to receive tirbanibulin or vehicle (5-day once-daily self-application). Primary endpoint was complete clearance of AK at Day 57. Safety assessments included local skin reactions (LSRs) and adverse events.
Microvesicle particles (MVP) are nano-sized extracellular vesicles, secreted in response to stimuli such as therapeutic agents by a variety of cell types including tumor cells. MVP are involved in mediating several cellular responses including modifying tumorigenicity or sensitivity of therapeutic agents. Studies, including ours, have shown that tumor cells expressing a G-protein coupled, platelet-activating factor-receptor (PAF-R) augments pro-oxidative stressors including chemotherapy-mediated MVP release.
Lung cancer remains the leading cause of cancer-related deaths, with low response rates to the current treatment options, indicating the need to explore potential factors, involved in lung cancer growth or impeding the efficacy of therapeutic agents. Studies, including ours, have shown the critical roles of a G-protein coupled, platelet-activating factor-receptor (PAF-R) signaling in augmenting tumor growth or limiting therapy effectiveness in various experimental cancer models. While several mechanisms of the PAF-R pathway have been proposed, its effect with microRNAs (miRs) has not been studied.
Bunkered in barrier tissue, tissue-resident memory T (TRM) cells are strategically positioned to react quickly to tissue perturbations, such as infection, injury, or cancer. Recent studies have highlighted a potential role for TRM cells as a targetable T cell population due to their abundance in most tissues. To better understand the role TRM cells play in the antitumor immune response, we developed a targeted CRISPR screen to identify the essential genes regulating the TRM-response to tumors. We first developed a murine tumor model system in which OT-I cells could be adoptively transferred and re-isolated from tumors.
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Background: Moh’s micrographic surgery (MMS) is the gold standard treatment for non-melanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Despite the advantages of MMS, the technique also has limitations. The procedure can be time-consuming and, due to the bulky nature of many cutaneous tumors, appropriately sectioning and flattening the specimen for cryosection without omitting tissue is difficult. A novel method has recently been proposed as an alternative to the traditional MMS approach.
Recent studies have provided a better understanding of cytokines playing a role in pruritus (itch), a cardinal feature in atopic dermatitis (AD). Among these cytokines, IL-13 is a key mediator of multiple pro-inflammatory processes in AD. Other type-2 cytokines, such as TSLP, IL-33, and IL-4 modulate neurons directly, in addition to their pro-inflammatory effects. Lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13, is under investigation for the treatment of moderate-to-severe AD.
Chronic pruritus of unknown origin (CPUO) is pruritus lasting greater than 6 weeks that is not linked to a causal disease process. With a lack of approved therapies, CPUO is extremely difficult to manage. We thus conducted a retrospective review of 23 patients collecting demographics, medical history, laboratory data including complete blood count with differential, pruritus characteristics, and response to treatment. Of these patients, those with an absolute eosinophil count above 0.30 K/cu mm, eosinophil percent above 4%, or pronounced eosinophils on skin biopsy were identified.
Background: We previously nominated PD-1+ cell densities in pre-treatment tumor specimens as a potential biomarker for response to pembrolizumab (anti-PD-1) in patients with advanced Merkel cell carcinoma (MCC). Here, we used multiplex immunofluorescence (mIF) in a separate cohort of MCC patients treated with anti-PD-1 to determine which immune cell subset(s) contribute PD-1 to the tumor microenvironment (TME). We also characterized PD-1 expression intensity on lymphocytes, as an indication of their functional state, and tested for an association with anti-PD-1 response.
Wrinkling is the hallmark of skin aging. We have previously reported that perioral wrinkling is more severe in females; however the molecular basis for this is unknown. We enrolled 12 subjects (n=6 male/female) age 54-86 with Griffith’s photoaging severity grade between 4 and 8 (0=none, 8=severe) and took biopsies from both the perioral and periocular region. Using qPCR, we assessed RNA expression levels of collagen I, collagen III, cysteine-rich angiogenic inducer 61 (CYR61), and insulin like growth factor 1 (IGF-1).
Purpose: To investigate the functionality of Fluorescence Imitating Brightfield Imaging (FIBI) for imaging skin tissue samples. Methods: The surfaces of three (with more to follow) skin samples from the UC Davis Dermatopathology tissue bank were deparaffinized using xylene and ethanol washes, then stained with hematoxylin, Scott’s bluing reagent and eosin. A color camera captured images from 405 nm visible range (blue) excitation light illuminating the specimens. Standard hematoxylin and eosin (H&E) slides were cut from specimens prior to deparaffinization and compared to FIBI images.
Objective To identify anti-MDA5 antibody subtype (IgG, IgA, IgM) and anti-MDA5 IgG subclasses, and to investigate their association with clinical severity. Methods Clinical features, laboratory findings and serum of 36 DM/CADM patients with anti-MDA5 antibody positive were collected and analyzed. Anti-MDA5 IgG was measured by enzyme-linked immunosorbent assay and line-blot immunoassay. Anti-MDA5 subtype (IgG, IgA, IgM) and anti-MDA5 IgG subclasses were measured by enzyme-linked immunosorbent assay.
Deep convolutional neural networks (CNNs) can outperform dermatologists on image classification. However, their performance in a real-world setting, where image capture is subject to variations in lighting, zoom, focus, etc. is not well studied. Recent work in the machine learning community has reported that CNNs predictions are not stable to perturbations of the input image, e.g. a simple rotation. Standardized metrics of model robustness, to be reported in addition to accuracy, are needed to assess the readiness of dermatologist-level CNNs for clinical use.
OBJECTIVE: To analyze the changes of serum metabolites of patients with psoriasis after IL-17A monoclonal antibody (mAb) treatment and halomethasone treatment, and to compare the effects of the two treatment methods on patients' systemic metabolism. METHODS: Metabolomics techniques based on gas chromatography-mass spectrometry were used to analyze the serum metabolites before and after the treatments in 32 patients treated with IL-17A mAb and 16 patients treated with halomethasone. RESULTS: 19 serum differential metabolites were screened out before and after IL-17A mAb treatment, while 9 serum differential metabolites were screened out after treatment with halameasone.