Dermal Cell News 3.30 September 11, 2017 | |
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TOP STORYResearchers Discover Why Redheads Are More Prone to Melanoma Researchers have shown that there is a way to reduce cancer risk in redheads. Specifically, they proved that melanocortin 1 receptor (MC1R), the protein involved in pigmentation, is affected by a special modification process called palmitoylation that is critical for its function. By enhancing palmitoylation in the variant, MC1R proteins of redheads cancer risk can be reduced. [Press release from Boston University School of Medicine discussing online prepublication in Nature] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DERMAL STEM CELLS & TISSUE REGENERATIONCK1α Ablation in Keratinocytes Induces p53-Dependent, Sunburn-Protective Skin Hyperpigmentation To characterize the role of casein kinase 1α (CK1α) (encoded by Csnk1a1) in skin physiology, the authors crossed mice harboring floxed Csnk1a1 with mice expressing K14–Cre–ERT2 to generate mice in which tamoxifen induces the deletion of Csnk1a1 exclusively in keratinocytes. To clarify the putative role of p53 in epidermal hyperpigmentation, they established K14–Cre–ERT2 CK1α/p53 double-knockout mice and found that coablation failed to induce epidermal hyperpigmentation, demonstrating that it was p53-dependent. [‎Proc Natl Acad Sci USA] Abstract FOXO1 Deletion in Keratinocytes Improves Diabetic Wound Healing through MMP9 Regulation To address mechanisms of impaired re-epithelialization, investigators examined matrix metalloproteinase 9 (MMP9) expression in vivo in full thickness dermal scalp wounds created in experimental K14.Cre+.Foxo1L/L mice with lineage-specific Cre recombinase deletion of floxed FOXO1 and compared the results to control littermates. MMP9 was induced during wound healing but at a significantly higher level in diabetic compared to normal wounds. [Sci Rep] Full Article The authors identified a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells expressed Tbx3, which was necessary for their propagation to drive skin expansion. [Sci Rep] Full Article SKIN CANCERS & DISORDERSResearchers identified mutations in the ACTRT1 gene, which encodes actin-related protein T1, in two of the six families with Bazex–Dupré–Christol syndrome that were examined in this study. Exogenous expression of ACTRT1 reduced the in vitro and in vivo proliferation rates of cell lines with aberrant activation of the Hedgehog signaling pathway. [Nat Med] Abstract Investigators compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines or in bulk mouse tumors. [Cancer Discov] Abstract | Full Article ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma Scientists assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. [Cancer Res] Abstract In exploring YB-1 targeting, the authors discovered that the shrimp microRNA, miR-S8, could suppress human YB-1 expression in melanoma stem-like cells. Mechanistic investigations revealed that miR-S8 recognized the 3’UTR of YB-1 mRNA and mediated its degradation. [Cancer Res] Abstract To unravel BRAF inhibitor (BRAFi) resistance mechanisms, researchers performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. [Cell Death Dis] Full Article Role of Adipose Tissue in Melanoma Cancer Microenvironment and Progression Scientists investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system. They studied the morphological and functional properties of 3T3-L1 adipocytes before and after co-culture with A375 melanoma cells, in order to assess the role of adipocytes on melanoma migration. [Int J Obes (Lond)] Abstract ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway Zinc finger 23 (ZNF23) was elevated in adjacent normal skin tissues compared with melanoma tissues. Patients with low level of ZNF23 expression exhibited higher incidence of lymphoid metastasis, thicker size of tumors and worse outcome. [Cell Physiol Biochem] Full Article | |
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REVIEWSAtopic Dermatitis and Psoriasis: Two Different Immune Diseases or One Spectrum? Psoriasis and atopic dermatitis (AD) can be viewed as distinct diseases with differing clinical, tissue, and molecular disease phenotypes, but this view does not account for specific subtypes of AD, including Asian-origin, intrinsic, and pediatric AD, that have a prominent IL-17 component and also tissue patterning that overlaps with distinctive psoriasis histopathology. [Curr Opin Immunol] Abstract Visit our reviews page to see a complete list of reviews in the dermal cell research field. | |
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SCIENCE NEWSBristol-Myers Squibb Company announced that treatment with Opdivo 3 mg/kg resulted in a significant improvement in recurrence-free survival compared to Yervoy 10 mg/kg in patients with stage IIIb/c or stage IV melanoma following complete surgical resection. [Press release from Bristol-Myers Squibb Company discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release Phase III COLUMBUS Part 2 Results in BRAF-Mutant Melanoma Presented Array BioPharma and Pierre Fabre announced results from Part 2 of the Phase III COLUMBUS study evaluating binimetinib, a MEK inhibitor, and encorafenib, a BRAF inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma. [Press release from Array BioPharma discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release Incyte Corporation announced updated data from the ongoing Phase I/II ECHO-202 trial evaluating epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with KEYTRUDA®, an anti-PD-1 therapy marketed by Merck & Co., Inc., in patients with advanced melanoma. [Press release from Incyte Corporation discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release Idera Pharmaceuticals, Inc. announced final results from the dose-selection phase of an ongoing Phase I/II trial investigating IMO-2125, Idera’s intratumorally-delivered toll-like receptor 9 agonist, in combination with ipilimumab, manufactured by Bristol-Myers Squibb. [Press release from Idera Pharmaceuticals, Inc. discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release NewLink Genetics Corporation announced updated data from the ongoing Phase II NLG2103 study of indoximod, NewLink Genetics’ IDO pathway inhibitor, in combination with the PD-1 pathway inhibitor, KEYTRUDA. [Press release from NewLink Genetics Corporation discussing research presented at the 2017 International Cancer Immunotherapy Conference, Frankfurt/Mainz] Press Release | |
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INDUSTRY NEWSLasker Prizes Recognize Work on Cell Growth, Cancer Prevention, and Reproductive Care The Albert and Mary Lasker Foundation announced its three annual prizes, each of which comes with a $250,000 award. Regarded as the United States’s most prestigious biomedical research awards, the Laskers often precede a Nobel Prize in Physiology or Medicine: Eighty-seven Lasker laureates have gone on to win a Nobel. [ScienceInsider] Editorial | Press Release The 2017 Balzan Prizewinners Announced in Milan The 2017 Balzan Prizewinners were announced in Milan by the Chairman of the Balzan General Prize Committee, Salvatore Veca, together with the President of the Balzan “Prize” Foundation, Enrico Decleva, at the Corriere della Sera Foundation. [The International Balzan Foundation (EurekAlert!)] Press Release CPRIT Awards More than $9 Million in Cancer Research Grants to Texas A&M The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded eight research grants to Texas A&M University totaling more than $9 million. The grants are among 60 new awards totaling more than $102 million that CPRIT recently announced in Austin. [Texas A&M University] Press Release For more than two decades, Wei Chen, Ph.D., professor of biomedical engineering and dean of the College of Mathematics and Science at the University of Central Oklahoma (UCO), has dedicated his time and research to developing a new type of cancer treatment to treat late-stage, metastatic cancers. Those efforts recently got a big boost, as Chen received the first and only National Institutes of Health Research Project Grant awarded to a non-research institution in the state of Oklahoma. [University of Central Oklahoma] Press Release AbbVie’s Upadacitinib (ABT-494) Meets Primary Endpoint in Phase IIb Study in Atopic Dermatitis AbbVie announced positive top-line results from the Phase IIb randomized, placebo-controlled, dose-ranging study of upadacitinib, an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis not adequately controlled by topical treatments, or for whom topical treatments were not medically advisable. [AbbVie Inc.] Press Release Regeneron Pharmaceuticals, Inc. and Sanofi announced that the FDA has granted Breakthrough Therapy designation status to cemiplimab for the treatment of adults with metastatic cutaneous squamous cell carcinoma (CSCC) and adults with locally advanced and unresectable CSCC, the second deadliest skin cancer after melanoma. Cemiplimab is an investigational human, monoclonal antibody targeting PD-1. [Regeneron Pharmaceuticals, Inc.] Press Release Ortho Dermatologics, a division of Valeant Pharmaceuticals International, Inc., announced that it has submitted a New Drug Application to the FDA for IDP-118 lotion. IDP-118 is the first and only topical lotion that contains a unique combination of halobetasol propionate and tazarotene for the treatment of plaque psoriasis. [Valeant Pharmaceuticals International, Inc.] Press Release Iovance Biotherapeutics, Inc. announced that the FDA has granted Fast Track designation for LN-144, the company’s adoptive cell therapy using its tumor-infiltrating lymphocyte technology, for the treatment of advanced melanoma. [Iovance Biotherapeutics, Inc.] Press Release | |
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POLICY NEWSThe Minister of Science, Kirsty Duncan, announced $515 million in support for fundamental research through the Natural Sciences and Engineering Research Council of Canada’s (NSERC) 2017 competition for the Discovery Grants program, scholarships and fellowships. This is NSERC’s largest annual investment, and it assists researchers by offering financial support though scholarships, fellowships, research supplements, and equipment grants. [Natural Sciences and Engineering Research Council of Canada] Editorial Senate Panel Seeks Middle Ground on Human Fetal Tissue Research and Abortion A Senate spending panel countered a move by its House of Representatives counterpart to quash federal funding for research that uses human fetal tissue from elective abortions. The move sets up a conflict that will need to be resolved when lawmakers meet later this year to hash out differences between the House and Senate bills, which will provide funding for the National Institutes of Health in the 2018 fiscal year. [ScienceInsider] Editorial South Korean Researchers Lobby Government to Lift Human-Embryo Restrictions More than a decade after a fraud scandal in stem-cell science rocked South Korea, scientists in the field are ramping up pressure on the government to relax the country’s strict regulations on human-embryo research — which many researchers label a ban. [Nature News] Editorial Italian Scientists Welcome Surprise €400 Million Boost for Basic Research Italian scientists received a welcome surprise when Valeria Fedeli, the minister for education, university, and research, announced that Italy will put an extra €400 million into its main basic science fund, the Research Projects of National Interest (PRIN). The money, to be spent over three years, will more than quadruple PRIN’s annual funding. [ScienceInsider] Editorial
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EVENTSNEW Keystone Symposia: Precision Medicine in Cancer Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Molecular Oncology and Mouse Modeling (Moffitt Cancer Center) NEW Research Associate – Cancer Cell Metastasis (Imperial College London) PhD Position – Molecular Biology (University of Luxembourg) Research Fellow – Melanoma (Dana-Farber Cancer Institute) Postdoctoral Fellowship – Melanoma (Harvard Medical School) PhD Studentship – Skin Cancer & Aging (CRUK Manchester Institute) Postdoctoral Position – Immune Cells and Keratinocytes in Psoriasis (University of Geneva) Postdoctoral Position – Skin Wound Healing and Inflammation (Inserm) Research Technician – Adult Skin Stem Cells (Howard Hughes Medical Institute) 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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