Dermal Cell News Volume 3.07 | Mar 6 2017

TOP STORY

Tissue-Scale Coordination of Cellular Behavior Promotes Epidermal Wound Repair in Live Mice

Investigators captured the spatiotemporal dynamics of individual epithelial behaviors by imaging wound re-epithelialization in live mice. Differentiated cells migrated while the rate of differentiation changes depended on local rate of migration and tissue architecture. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

PNPLA1 Has a Crucial Role in Skin Barrier Function by Directing Acylceramide Biosynthesis

Scientists showed that patatin-like phospholipase domain-containing 1 (PNPLA1), an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. [Nat Commun] Full Article

Defining Stem Cell Dynamics and Migration during Wound Healing in Mouse Skin Epidermis

Researchers showed the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, they identified the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. [Nat Commun] Full Article

Cryptomphalus aspersa Mollusc Egg Extract Promotes Regenerative Effects in Human Dermal Papilla Stem Cells

Investigators tested, by an in vitro approach, whether a natural extract derived from eggs of the mollusc C. aspersa (e-CAF) can enhance the mobilization of human hair dermal papilla cells (HHDPCs) and play a role on tissue repair and regeneration. e-CAF promoted proliferation and migration of HHDPCs cells in a time- and dose-dependent manner; it also increased the migratory behavior and the expression of adhesion molecules. [Int J Mol Sci] Full Article

SKIN CANCERS & DISORDERS

SIRT1, a Class III Histone Deacetylase, Regulates LPS-Induced Inflammation in Human Keratinocytes and Mediates the Anti-Inflammatory Effects of Hinokitiol

The authors report that hinokitiol, a tropolone-related natural compound that exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties in various cell types, can modulate the inflammatory responses of primary human keratinocytes challenged with lipopolysaccharide. [J Invest Dermatol] Abstract

TFAP2 Paralogs Regulate Melanocyte Differentiation in Parallel with MITF

To identify genes with TFAP2A-dependent expression in melanocytes, scientists profiled zebrafish tissue and mouse melanocytes deficient in Tfap2a, and found that expression of a small subset of genes underlying pigmentation phenotypes was TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. [PLoS Genet] Full Article

2-O-Methylmagnolol Upregulates the Long Non-Coding RNA, GAS5, and Enhances Apoptosis in Skin Cancer Cells

Magnolol, a hydroxylated biphenol compound isolated from the bark of Magnolia officinalis, has been shown to exhibit anti-proliferative effect in various cancer cells, including skin cancer cells. The authors report that 2-O-methylmagnolol displays improved antitumor activity against skin cancer cells compared to magnolol both in vitro and in vivo. [Cell Death Dis] Full Article

COX-2 Expression Positively Correlates with PD-L1 Expression in Human Melanoma Cells

Researchers investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. The BRAF^V600E A375 and NRAS^Q61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. COX-2 expression correlated with and modulated PD-L1 expression in melanoma cells. [J Transl Med] Full Article

IRE1α-XBP1 Pathway Promotes Melanoma Progression by Regulating IL-6/STAT3 Signaling

IL-6 expression levels were determined in both melanocytes and melanoma cells overexpressing the spliced form of XBP1 (XBP1s). The mRNA and protein expression levels of XBP1s were significantly elevated in human melanoma tissues and cell lines compared with normal tissues or melanocytes, thus indicating the activation of the IRE1α-XBP1 branch in melanoma. [J Transl Med] Full Article

Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells

Investigators examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1, lysyl oxidase-like 2, and urokinase plasminogen activator receptor. [Int J Mol Sci] Full Article

The Master Role of Microphthalmia-Associated Transcription Factor in Melanocyte and Melanoma Biology

The authors review basic features of microphthalmia-associated transcription factor biological function and highlight key unresolved questions regarding this remarkable transcription factor. [Lab Invest] Full Article

Minimal Residual Disease in Melanoma: Circulating Melanoma Cells and Predictive Role of MCAM/MUC18/MelCAM/CD146

Overall and disease-free survival have been correlated with the presence of circulating melanoma cells (CMCs). Specific melanoma antigens, in particular MCAM (MUC18/MelCAM/CD146), could be a potentially useful tool to isolate CMCs as well as be a prognostic, predictive biomarker. [Cell Death Discov] Full Article

Visit our reviews page to see a complete list of reviews in the dermal cell research field.

Oral OTEZLA^® (Apremilast) Demonstrated Significant Improvement versus Placebo in Trial of Patients with Moderate Plaque Psoriasis Who Were Naïve to Systemic and Biologic Therapy

Celgene Corporation announced that results from its Phase IV UNVEIL trial evaluating OTEZLA^®, the company’s oral, selective inhibitor of phosphodiesterase 4, in patients with moderate plaque psoriasis with a body surface area of 5-10 percent [Press release from Celgene Corporation discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

Regeneron and Sanofi Announce Presentation of Positive Data from Long-Term Pivotal Phase III CHRONOS Study of DUPIXENT^® (Dupilumab) in Moderate-to-Severe Atopic Dermatitis

Regeneron Pharmaceuticals, Inc. and Sanofi presented detailed results from the one-year Phase III CHRONOS study, which showed that patients receiving the investigational drug DUPIXENT with topical corticosteroids (TCS) achieved significantly improved measures of overall disease severity compared to TCS alone in adults with uncontrolled moderate-to-severe atopic dermatitis. [Press release from Regeneron Pharmaceuticals, Inc. discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

LEO Pharma Announces Positive Results from Phase IIb Clinical Study for Tralokinumab in Atopic Dermatitis

LEO Pharma announced positive results from a Phase IIb dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate to severe atopic dermatitis, a serious and chronic form of eczema. [Press release from LEO Pharma discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

Galectin’s GR-MD-02 Demonstrates Efficacy in Patients with Moderate to Severe Plaque Psoriasis

Galectin Therapeutics Inc. announced results from an exploratory, Phase IIa clinical trial with GR-MD-02 in patients with moderate-to-severe plaque psoriasis. Data showed no serious adverse events and achieved an average Psoriasis Area and Severity Index reduction of over 50% in all patients that participated in the 24-week trial, further demonstrating the safety and efficacy of this novel investigational drug in this patient population. [Press release from Galectin Therapeutics Inc. discussing research to be presented at the Maui Derm for Dermatologists, Maui] Press Release

Samumed Presented Data on Increases in Hair Follicles Observed in Its Phase II Biopsy Study for a Potential Treatment of Androgenetic Alopecia (AGA)

Samumed, LLC presented safety and efficacy results from a Phase II scalp biopsy study for its AGA program. The results suggested that Samumed’s investigational drug, a topical solution of the novel small molecule compound SM04554, may be the first treatment causing follicular neogenesis. [Press release from Samumed, LLC discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

Castle Creek Pharmaceuticals Announces Presentation of Phase II Clinical Data for Diacerein 1% Ointment in Treatment of Epidermolysis Bullosa Simplex

Castle Creek Pharmaceuticals announced that results from a placebo-controlled clinical trial for topical diacerein 1% in the treatment of epidermolysis bullosa simplex were presented. Results, which were previously reported, showed a 60 percent reduction in blistering among patients treated with diacerein 1% versus a 15 percent reduction in the placebo group at four weeks. [Press release from Castle Creek Pharmaceuticals (PR Newswire Association LLC.) discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

Dynavax Presents Promising Clinical Data from Lead Immuno-Oncology Candidate, SD-101

Dynavax Technologies Corporation announced the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an ongoing Phase Ib/II study investigating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with KEYTRUDA^®, an anti-PD-1 therapy developed by Merck. [Press release from Dynavax Technologies Corporation discussing research to be presented at the International Congress on Targeted Anticancer Therapies, Paris] Press Release

Ablynx’s Partner, Merck KgaA, Has Presented New Data from a Phase Ib Psoriasis Study of the Bi-Specific Anti-Il-17a/F Nanobody

Ablynx announced that its partner, Merck KGaA, presented new data from a Phase Ib study demonstrating strong efficacy with the bi-specific anti-IL-17A/F Nanobody^® in patients with moderate-tosevere chronic plaque psoriasis. [Press release from Ablynx discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

Novartis’ Cosentyx Shows Almost All Psoriasis Patients Rapidly Regain Skin Clearance following a Treatment Pause

Novartis announced a new analysis showing that moderate-to-severe psoriasis patients treated with Cosentyx^® rapidly regain clear or almost clear skin following relapse during a treatment pause. [Press release from Novartis discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

New Head-to-Head Data Shows Significantly Higher Response Rates for Lilly’s Taltz^® (Ixekizumab) Compared to Stelara^® (Ustekinumab) in Patients with Moderate-to-Severe Plaque Psoriasis

Eli Lilly and Company announced that patients with moderate-to-severe plaque psoriasis treated with Taltz^® demonstrated superior efficacy at 24 weeks compared to patients treated with Stelara^®. [Press release from Eli Lilly and Company discussing research presented at the 75^th American Academy of Dermatology (AAD) Annual Meeting, Orlando] Press Release

New Results from Second Phase III Study Show Significant Efficacy of Guselkumab and Superiority versus Humira^® in Treatment of Moderate to Severe Plaque Psoriasis

Janssen Research & Development, LLC announced new findings from two pivotal Phase III studies reporting the efficacy and safety of guselkumab in the treatment of adults with moderate to severe plaque psoriasis. Data from the VOYAGE 2 study showed that patients treated with guselkumab experienced significant improvements in skin clearance and other measures of disease activity compared with placebo, and significantly greater improvements compared with the anti-tumor necrosis factor-alpha treatment Humira^®. [Janssen Global Services, LLC] Press Release

Immune Pharmaceuticals Reports Encouraging Preliminary Data with Bertilimumab in an Open Label Phase II Study in the Rare Dermatological Auto-Immune Disease, Bullous Pemphigoid

Immune Pharmaceuticals Inc. announced that it has broadened enrollment eligibility criteria based on the data reported from three patients that have completed treatment to date in its ten-patient open label study of bertilimumab in the treatment of bullous pemphigoid. In those patients, the Bullous Pemphigoid Disease Activity Index was reduced by an average of 84% and oral prednisone was tapered down to 10 mg or less. No significant adverse events were reported. [Immune Pharmaceuticals Inc.] Press Release

What Trump’s New Travel Ban Means for Science

US President Donald Trump has signed a revised version of his controversial travel ban. The policy, issued on 6^th March, exempts citizens of Iraq and people who have already been issued US visas — including those with green cards. Like the first order, which Trump signed on 27^th January, the revised policy bars citizens of Iran, Libya, Somalia, Sudan, Syria and Yemen from the US for 90 days. [Nature News] Editorial

Senior Republican Lawmaker Has Some Advice for U.S. Science Marchers

The chairman of a congressional spending panel that oversees a wide swath of U.S. science agencies has some unusual advice for scientists planning to march on 22 April: Don’t talk about research. Instead, demand that Congress find a way to cut mandatory spending programs. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Epithelial Differentiation & Keratinization
May 7-12, 2017
Barga, Italy

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Fellow – Metastatic Melanoma (Inserm)

Postdoctoral – Tumor Biology (Helmholtz Association)

Postdoctoral Position – Translational Melanoma (University of Gothenburg)

Postdoctoral Associate – Cancer Biology (University of Florida)

Faculty Member – Melanoma (Oregon Health and Science University)

Postdoctoral Fellow – Cutaneous Lymphoma (City of Hope)

Bioinformatics Scientist – Cancer Biology (Genentech, Inc.)

Principal Scientist – Oncology (Janssen)

Tenure-Track Faculty Positions – Department of Biomedical Sciences (University of Pennsylvania)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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