Dermal Cell News 4.30 September 10, 2018 | |
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TOP STORYThe Alchemy of Healing: Researchers Turn Open Wounds into Skin Plastic surgery to treat large cutaneous ulcers, including those seen in people with severe burns, bedsores or chronic diseases such as diabetes, may someday be a thing of the past. Scientists at the Salk Institute have developed a technique to directly convert the cells in an open wound into new skin cells. [Press release from the Salk Institute for Biological Studies discussing online prepublication in Nature] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DERMAL STEM CELLS & TISSUE REGENERATIONInvestigators used consecutive serum deprivation and re-stimulation to reconstruct biphasic collective migration and proliferation in cultured sheets of human keratinocytes. In this system, a burst of long-range coordinated locomotion was rapidly generated throughout the cell sheet in the absence of wound edges. [Nat Commun] Full Article Investigators showed that junctional adhesion molecule-A (JAM-A) was significantly expressed in normal skin epidermis. In a rat wound model, they showed that the absence of JAM-A significantly promoted the wound healing process, while the use of PF-562271 or Erk1/2 inhibitor PD98059 repressed those effects. [Cell Death Dis] Full Article Establishment of Keratinocyte Cell Lines from Human Hair Follicles Keratinocytes derived from cultured hair follicles and interfollicular epidermis were immortalized by ectopic expression of SV40 and hTERT. The generated keratinocyte cell lines differentiated into stratified epidermis with well-defined stratum granulosum and stratum corneum in organotypic human skin models. [Sci Rep] Full Article Researchers observed that both TRAIL and NOXA expression increased in cells exposed to ultraviolet B (UVB) and the TOR kinase inhibitor Torin 2. NOXA knockdown reversed the sensitization to UVB-induced apoptosis caused by mTORC2 inhibition. In contrast, loss of TRAIL by either knockdown or knockout actually enhanced expression of nuclear FOXO3a, which maintained apoptosis. [Cell Signal] Abstract | Graphical Abstract Suppression of Wnt/β-Catenin Signaling by EGF Receptor Is Required for Hair Follicle Development Genetic ablation of EGFR in mice resulted in increased mitotic activity in matrix cells, apoptosis in hair follicles and impaired differentiation of epithelial lineages that form hair. Using primary keratinocytes, investigators linked ligand-induced EGFR activation to suppression of nascent mRNA synthesis of Wnt genes. [Mol Biol Cell] Abstract SKIN CANCERS & DISORDERSBH3 Mimetics Induce Apoptosis Independent of DRP-1 in Melanoma Researchers found that BH3 mimetic combination killed both melanoma-initiating cells (MICs) and non-MICs in all cell lines and patient samples irrespective of the mutation status or relapsed state. Unexpectedly, the major pro-apoptotic proteins, NOXA and BIM, were not necessary for the combination-induced cell death. The combination impeded the activation of dynamin-related protein 1 (DRP-1), and inhibition of DRP-1 further enhanced apoptosis. [Cell Death Dis] Full Article Tissue-Engineered 3D Melanoma Model with Blood and Lymphatic Capillaries for Drug Development Scientists strived to mimic the melanoma microenvironment in vitro as an alternative to animal testing. Major components of the tumor microenvironment such as capillaries, human extracellular matrix, a stratified epidermis and basement membrane were recapitulated in vitro. Chronic treatment with vemurafenib was applied to the model and elicited a dose-dependent response on proliferation and apoptosis. [Sci Rep] Full Article ROCK Inhibitor Enhances the Growth and Migration of BRAF Mutant Skin Melanoma Cells Rho Kinase (ROCK) inhibitor Y-27632 increased the growth and migration of BRAF mutated melanoma cells, but had negative effect on wild type melanoma cells or primary melanocytes. Investigators discovered that Y-27632 enhanced the growth of BRAF mutated melanoma cells through increased ATK and ERK activity. [Cancer Sci] Abstract Researchers showed that a high-cholesterol diet aggravated psoriasis-like phenomena in imiquimod-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxidized low-density lipoprotein (oxLDL) increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. [Int J Mol Sci] Full Article Ruxolitinib Inhibits Cyclosporine-Induced Proliferation of Cutaneous Squamous Cell Carcinoma Cyclosporine A (CSA) and IL-22 exacerbated aggressive behavior in squamous cell carcinoma. In nude mice engrafted with human A431 cells, IL-22 and CSA treatment increased tumor growth and upregulated the IL-22 receptor, JAK1, and STAT1/3 expression. Ruxolitinib treatment significantly reduced tumor volume and reversed the accelerated tumor growth. [JCI Insight] Full Article Subscribe to one of our other 19 science newsletters such as Extracellular Matrix News & Cancer Stem Cell News. | |
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REVIEWSThe authors summarize the importance of major signaling pathways (MAPK, PI3K-Akt, Wnt, NF-kB, JAK-STAT, TGF-b and Notch) in skin homeostasis and melanoma progression. Most of the available and developing melanoma therapies, correlated with these signaling cascades, are further discussed. [Biosci Rep] Abstract | Full Article Visit our reviews page to see a complete list of reviews in the dermal cell research field. | |
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INDUSTRY NEWSTGen-Led Study of Metastatic Melanoma Secures $2 Million Grant Some of the nation’s top biomedical institutes – led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope – have received a $2 million federal grant towards discovering a new way to detect and track metastatic melanoma and understand how it escapes treatment. [Translational Genomics Research Institute] Press Release Novartis announced that the European Commission has approved Tafinlar® in combination with Mekinist® for the adjuvant treatment of stage III patients with BRAF V600 mutation-positive melanoma after complete surgical resection. [Novartis AG] Press Release Merck announced that the FDA has accepted and granted priority review for a new supplemental Biologics License Application seeking accelerated approval for KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. [Merck & Co., Inc.] Press Release Ortho Dermatologics announced that the FDA has accepted the resubmitted New Drug Application for DUOBRII®1 lotion for the topical treatment of plaque psoriasis. [Ortho Dermatologics] Press Release | |
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POLICY NEWSPeer Reviewers in Developing Nations Are Underrepresented, Report Suggests Combined, scientists spend nearly 70 million hours peer reviewing manuscripts for scholarly journals every year, a new report says. But too much of the onus rests on researchers in wealthy countries, according to the report by the company Publons—based in London and Wellington—which enables researchers to track and claim credit for the peer reviews they perform. [ScienceInsider] Editorial Top Cancer Researcher Called Out for Not Disclosing Conflicts in Medical Journals Medical journals and professional societies require study authors and presenters to disclose conflicts of interest, but this didn’t stop José Baselga, M.D., who heads up research at Memorial Sloan Kettering Cancer Center, from fudging his disclosures. [Fierce Biotech] Editorial
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EVENTSNEW Lorne Cancer Conference 2019 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Associate Researcher – Inflammatory Skin Diseases (Icahn School of Medicine at Mount Sinai) NEW Postdoctoral Fellow – Skin Cancer (Stanford University School of Medicine) Postdoctoral Studies – Microbiology and Innate Immunity in Psoriasis (Karolinska Institutet) Research /Senior Scientist – Modeling & Simulation (Certara) Post-doctoral Positions – Cancer Genetics/Genomics (University of Pennsylvania) Post-Doctoral Scientist – Novel T Cell Based Cancer Therapies (Netherlands Cancer Institute) Associate Professorships – Regenerative Medicine (University of Pavia) Associate Professor or Professor – Skin Cancer (The University of Texas M.D. Anderson Cancer Center) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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