Dermal Cell News Volume 3.11 | Apr 3 2017

TOP STORY

Skin Cancer Finding Provides Hope for Patients with Rare Type of Melanoma

A team of researchers report a significant genetic association linked to an aggressive form of melanoma. Acral lentiginous melanoma is an uncommon type of melanoma that typically occurs on the palms and soles and is often difficult to treat. They identified a protein target that opens a window into the disease and may aid in diagnosis and, one day, lead to improved treatments. [Press release from the Translational Genomics Research Institute discussing online prepublication in Genome Research] Press Release | Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Simulated Microgravity Triggers Epithelial Mesenchymal Transition in Human Keratinocytes

Short exposure of cultured human keratinocytes to the Random Positioning Machine microgravity influences the cellular circadian clock oscillation. Investigators searched for changes on the regenerative ability and response to tissue damage of human epidermal cells through the analysis of the effects of the simulated microgravity on the re-epithelialization phase of the repair and wound healing process. [Sci Rep] Full Article

Role of Keratin 24 in Human Epidermal Keratinocytes

Researchers investigated the localization of keratin 24 (K24) within the epidermis and possible functions. K24 was found to be modestly overexpressed in senescent keratinocytes and was mainly restricted to the upper stratum spinosum of epidermis. The protein was required for terminal differentiation upon CaCl₂-induced differentiation. [PLoS One] Full Article

In Vitro Skin Models to Study Epithelial Regeneration from the Hair Follicle

Scientists compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or collagen-glycosaminoglycan dermal equivalent (C-GAG) with the epidermis generated in vivo using C-CAG. Keratinocytes explanted from the outer root sheath of PSU and THF in both DED and C-GAG but only formed a multilayered epidermis with PSU in DED. [PLoS One] Full Article

SKIN CANCERS & DISORDERS

Sox2 Is Dispensable for Primary Melanoma and Metastasis Formation

To study the requirement of Sox2 for melanoma formation, the authors performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, they conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. In both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. [Oncogene] Abstract

Sox2 Is Not Required for Melanomagenesis, Melanoma Growth and Melanoma Metastasis In Vivo

By using a mouse model in which BRaf^V600E mutation cooperates with Pten loss to induce the development of metastatic melanoma, scientists investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors treatments. They found that deletion of Sox2 specifically in Pten null and BRaf^V600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. [Oncogene] Abstract

Mitochondrial Complex I Inhibition Triggers a Mitophagy-Dependent ROS Increase Leading to Necroptosis and Ferroptosis in Melanoma Cells

Inhibition of complex I of the mitochondrial respiratory chain by BAY 87-2243 (BAY) triggers death of BRAF^V600E melanoma cell lines and inhibits in vivo tumor growth. Investigators studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential, increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. [Cell Death Dis] Full Article

p53 Targets TSPAN8 to Prevent Invasion in Melanoma Cells

The authors found that tetraspanin 8 (TSPAN8) promoter contains consensus-binding sites for p53 transcription factor. They demonstrated that p53 silencing was sufficient to turn on Tspan8 expression in non-invasive melanoma cells and that p53 acts as a direct transcriptional repressor of TSPAN8. [Oncogenesis] Full Article

Circulating microRNA-194 Regulates Human Melanoma Cells via PI3K/AKT/FoxO3a and p53/p21 Signaling Pathway

Investigators analyzed the role of microRNA-194 circulating regulated human melanoma cell growth. They found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group. [Oncol Rep] Full Article

MicroRNA-485-5p Represses Melanoma Cell Invasion and Proliferation by Suppressing Frizzled7

The authors aimed to explore the potential role and underlying mechanism of microRNA (miR)-485-5p in the regulation of melanoma development. They showed that miR-485-5p was significantly decreased in melanoma tissues and cell lines compared with their corresponding controls. [Biomed Pharmacother] Abstract

MiR-370 Functions as Oncogene in Melanoma by Direct Targeting Pyruvate Dehydrogenase B

Scientists investigated the function of miR-370 in melanoma and to explore the molecular mechanism underlying its function. The expression level of miR-370 was detected in melanoma tissues and cell lines by real-time quantitative polymerase chain reaction. They showed that miR-370 was upregulated in melanoma tissues compared with non-cancerous tissues. [Biomed Pharmacother] Abstract

Function and Clinical Implications of Long Non-Coding RNAs in Melanoma

The authors summarize the growing evidence of deregulated long non-coding RNAs (lncRNAs) expression in melanoma, which is linked to tumor growth and progression. They highlight specific molecular pathways and modes of action for some well-studied lncRNAs and discuss their potential clinical implications. [Int J Mol Sci] Full Article

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New Gene-Based Blood Tests Identify More Skin Cancers

Researchers at NYU Langone Medical Center and its Perlmutter Cancer Center, who led the study, say having quick and accurate monitoring tools for all types of metastatic melanoma may make it easier for physicians to detect early signs of cancer recurrence. The new blood tests, which take only 48 hours, were developed in conjunction with Bio-Rad Laboratories in Hercules, California. [Press release from NYU Langone Medical Center discussing research to be presented at the 2017 American Association for Cancer Research, Washington, D.C.] Press Release

Nanobiotix: The Independent Data Monitoring Committee Recommends the Continuation of the Ongoing Phase II/III Trial of NBTXR3 in Soft Tissue Sarcoma

NANOBIOTIX announced that the Independent Data Monitoring Committee (IDMC) has completed the interim evaluation of the Phase II/III trial results of NBTXR3 in soft tissue sarcoma. Based on the safety and available efficacy data, the IDMC has recommended the continuation of the Phase II/III trial of NBTXR3 in soft tissue sarcoma. [NANOBIOTIX] Press Release

Regeneron and Sanofi Announce FDA Approval of DUPIXENT^® (Dupilumab), the First Targeted Biologic Therapy for Adults with Moderate-to-Severe Atopic Dermatitis

Regeneron Pharmaceuticals, Inc. and Sanofi announced that the U.S. Food and Drug Administration approved DUPIXENT^® injection, the first and only biologic medicine approved for the treatment of adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. [Regeneron Pharmaceuticals, Inc.] Press Release

BAVENCIO^® (Avelumab) Approved for the Treatment of Metastatic Merkel Cell Carcinoma, Available for Order at Biologics, Inc.

Biologics, Inc. has been selected by EMD Serono to be a specialty pharmacy provider for BAVENCIO. Approved by the U.S. Food and Drug Administration, BAVENCIO is a programmed death ligand-1 blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma. [Biologics, Inc.] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the five billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

NEW Protein Aggregation in Health and Disease
June 11-16, 2017
Steamboat Springs, United States

NEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease
June 11-16, 2017
Snowmass Village, United States

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NEW Postdoctoral Fellow – Melanoma (Icahn School of Medicine at Mount Sinai)

Postdoctoral Research Fellow – Skin Epigenetics (Boston University)

Researcher and Teacher – Skin and Venereal Diseases (Humanitas University)

Postdoctoral Fellow/Research Assistant – Psoriasis (University of California, Davis)

Two Postdoctoral Positions – Melanoma (Moffitt Cancer and Research Institute)

Clinical Research Fellow – Melanoma (CRUK Manchester Institute)

Professorships – Tissue Engineering and Regenerative Medicine (The Chinese University of Hong Kong)

Postdoctoral Training Fellow – Aryl Hydrocarbon Receptor (The Francis Crick Institute)

Postdoctoral Fellowship – Atopic Dermatitis (Boston Children’s Hospital)

Junior Research Group Leader – Analytics and Toxicology (The Federal Institute for Risk Assessment)

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