Dermatology

Comparative transcriptional profiling of human merkel cells and merkel cell carcinoma
Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer that is predominantly caused by infection by the Merkel cell polyomavirus. The cell of origin for MCC is still debated because conflicting data suggest that MCC cells could be derived from Merkel cells (MCs) [1] or their precursors [2]. aggressive carcinoma characteristically occurs on sun-exposed areas of elderly white an...


Knockdown of lecithin retinol acyltransferase (LRAT) increases all-trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells
Retinoids such as all-trans retinoic acid (ATRA) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid-metabolizing enzyme known as lecithin retinol acyltransferase (LRAT) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all-trans retinol (ATRol). In this study, we show t...
Homology modeling and virtual screening of P-protein in a quest for novel antimelanogenic agent and In vitro assessments
An adequate knowledge on molecular mechanism of melanogenesis provides an opportunity to find the novel molecular targets for the discovery and development of new cosmetics. Among various genes the OCA2 is being essential for proper melanin synthesis and, mutation or deletion of this gene leads to Oculocutaneous albinism type 2. Thus, for this study the product of this gene i.e. P-protein was t...


Loss of cell invasiveness through PKC-mediated syndecan-1 downregulation in melanoma cells under anchorage-independency
Anchorage-independent survival is one of key features for malignant tumor cells. Whether specific gene alterations contributed by anchorage-independency would further affect metastatic phenotypes of melanoma cells was unclear. We adapted suspension culture of melanoma cells to establish anchorage-independency. The suspended melanoma cells lost their invasive abilities in vitro. Specific loss of...
C-CBL E3 Ubiquitin Ligase Is Overexpressed in Cutaneous T-Cell Lymphoma: Its Inhibition Promotes Activation-Induced Cell Death
Mycosis fungoides and Sézary syndrome are two major forms of cutaneous T–cell lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T-cell apoptosis is activation-induced cell death, which is triggered through the T-cell receptor (TCR). This results in upregulation of FAS ligand (FASL) and subsequent apoptosis through the FAS death receptor pathway. It ...


Toll-Like Receptor 3 Activation Is Required for Normal Skin Barrier Repair Following UV Damage
UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin ...
Comparison of Molecular Signatures from Multiple Skin Diseases Identifies Mechanisms of Immunopathogenesis
The ability to obtain gene expression profiles from human disease specimens provides an opportunity to identify relevant gene pathways, but is limited by the absence of data sets spanning a broad range of conditions. Here, we analyzed publicly available microarray data from 16 diverse skin conditions in order to gain insight into disease pathogenesis. Unsupervised hierarchical clustering separa...

Activin A Is Anti-Lymphangiogenic in a Melanoma Mouse Model
Melanoma spreads primarily to the sentinel lymph nodes, and its risk correlates with lymphangiogenesis, which is mainly driven by vascular endothelial growth factor (VEGF)-C. However, anti-lymphangiogenic factors are poorly characterized. We have shown in a melanoma model that Wnt1 reduces lymphangiogenesis by reducing VEGF-C expression. Screening this model for additional potentially anti-lymp...
POF1B Localizes to Desmosomes and Regulates Cell Adhesion in Human Intestinal and Keratinocyte Cell Lines
By means of morphological and biochemical criteria, we here provide evidence for the localization and function of premature ovarian failure, 1B (POF1B) in desmosomes. In monolayers of Caco-2 intestinal cells and in stratified HaCaT keratinocytes, endogenous POF1B colocalized with desmoplakin at desmosome plaques and in cytoplasmic particles aligned along intermediate filaments (IFs). POF1B pred...

Requirement of Gαi1/3–Gab1 Signaling Complex for Keratinocyte Growth Factor–Induced PI3K–AKT–mTORC1 Activation
Keratinocyte growth factor (KGF), also termed as fibroblast growth factor-7, promotes proliferation, migration, and adhesion of skin keratinocytes via binding to keratinocyte growth factor receptor (KGFR) and subsequent activation of downstream signaling including the PI3K-AKT-mTORC1 pathway. Here, we found that the α-subunits of the G proteins (Gαi1/3) and growth factor...
Genomic Profiling of Human Leishmania braziliensis Lesions Identifies Transcriptional Modules Associated with Cutaneous Immunopathology
The host immune response has a critical role not only in protection from human leishmaniasis but also in promoting disease severity. Although candidate gene approaches in mouse models of leishmaniasis have been extremely informative, a global understanding of the immune pathways active in lesions from human patients is lacking. To address this issue, genome-wide transcriptional profiling of Lei...

Immunotherapeutic strategies against mucormycosis in haematopoietic stem cell transplantation
Mucormycoses remain a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). In these patients, mortality rates of mucormycosis reach up to 90%, which is due, at least in part, to the severe and prolonged immunosuppression after transplantation. Although prolonged neutropaenia is one of the most important risk factors for mucormycosis, other cell...
Interaction of Zygomycetes with innate immune cells reconsidered with respect to ecology, morphology, evolution and infection biology: a mini-review
Zygomycetes are saprophytic fungi found ubiquitously in nature. Generally, fungi are considered as the most common microbes encountered by mammalian hosts due to its ubiquity in nature. Among the fungi, the Zygomycetes represent the most basal terrestrial lineage which can cause infections in humans. They comprise two orders, the Mucorales and the Entomophthorales, which contain human pathogeni...
A prospective study of cigarette smoking and basal cell carcinoma
To investigate the relationship between smoking and primary basal cell carcinoma (BCC), we analyzed data from a 16 year prospective study among randomly selected adults in Nambour, Queensland, Australia. Participants underwent a skin examination in 1992 and took part in an intervention study and follow-up. Information about complexion type and smoking habits including duration and number of ci...
Arterial Disease Ulcers, Part 2: Treatment
The purpose of this learning activity is to provide information about therapeutic clinical intervention options based on the pathophysiology of arterial ulcers. TARGET AUDIENCE:This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:Identify assess...