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https://www.readbyqxmd.com/read/29045843/high-throughput-functional-genetic-and-compound-screens-identify-targets-for-senescence-induction-in-cancer
#1
Liqin Wang, Rodrigo Leite de Oliveira, Cun Wang, João M Fernandes Neto, Sara Mainardi, Bastiaan Evers, Cor Lieftink, Ben Morris, Fleur Jochems, Lisa Willemsen, Roderick L Beijersbergen, René Bernards
Senescence is a proliferation arrest that can result from a variety of stresses. Cancer cells can also undergo senescence, but the stresses that provoke cancer cells to undergo senescence are unclear. Here, we use both functional genetic and compound screens in cancer cells harboring a reporter that is activated during senescence to find targets that induce senescence. We show that suppression of the SWI/SNF component SMARCB1 induces senescence in melanoma through strong activation of the MAP kinase pathway...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29042215/a-novel-stilbene-like-compound-that-inhibits-melanoma-growth-by-regulating-melanocyte-differentiation-and-proliferation
#2
Noah A Stueven, Nicholas M Schlaeger, Aaron P Monte, Sheng-Ping L Hwang, Cheng-Chen Huang
Melanoma is the most aggressive form of skin cancer. Current challenges to melanoma therapy include the adverse effects from immunobiologics, resistance to drugs targeting the MAPK pathway, intricate interaction of many signal pathways, and cancer heterogeneity. Thus combinational therapy with drugs targeting multiple signaling pathways becomes a new promising therapy. Here, we report a family of stilbene-like compounds called A11 that can inhibit melanoma growth in both melanoma-forming zebrafish embryos and mouse melanoma cells...
October 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29039788/impact-of-natural-compounds-on-dna-methylation-levels-of-the-tumor-suppressor-gene-rassf1a-in-cancer
#3
REVIEW
Reinhard H Dammann, Antje M Richter, Adriana P Jiménez, Michelle Woods, Miriam Küster, Chamindri Witharana
Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in the pathogenesis of human cancer. This silencing is accomplished by aberrant chromatin modifications including DNA hypermethylation of the gene promoter. One of the most frequently hypermethylated TSG in human cancer is the Ras Association Domain Family 1A (RASSF1A) gene. Aberrant methylation of RASSF1A has been reported in melanoma, sarcoma and carcinoma of different tissues. RASSF1A hypermethylation has been correlated with tumor progression and poor prognosis...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29036293/rare-germline-variants-in-known-melanoma-susceptibility-genes-in-familial-melanoma
#4
Alisa M Goldstein, Yanzi Xiao, Joshua Sampson, Bin Zhu, Melissa Rotunno, Hunter Bennett, Yixuan Wen, Kristine Jones, Aurelie Vogt, Laurie Burdette, Wen Luo, Bin Zhu, Meredith Yeager, Belynda Hicks, Jiali Han, Immaculata De Vivo, Stella Koutros, Gabriella Andreotti, Laura Beane-Freeman, Mark Purdue, Neal D Freedman, Stephen J Chanock, Margaret A Tucker, Xiaohong R Yang
Known high-risk cutaneous malignant melanoma (CMM) genes account for melanoma risk in < 40% of melanoma-prone families, suggesting the existence of additional high-risk genes or perhaps a polygenic mechanism involving multiple genetic modifiers. The goal of this study was to systematically characterize rare germline variants in 42 established melanoma genes among 144 CMM patients in 76 American CMM families without known mutations using data from whole-exome sequencing. We identified 68 rare (<0.1% in public and in-house control datasets) nonsynonymous variants in 25 genes...
October 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29036014/a-family-with-two-cases-of-melanocytic-tumors-and-fragile-x-syndrome
#5
Candice Lesage, Isabelle Coupier, Bernard Guillot
Fragile X syndrome (FXS), a leading cause of inherited intellectual disability, most commonly results from an expansion of the CGG trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene to more than 200 copies (full mutation). The FXS phenotype differs by sex and is associated with intellectual and cognitive impairment, characteristic physical features, epilepsy, and/or behavioral challenges including autism spectrum disorder. In this patient population, tumors involving blood cells, digestive organs, the central nervous system, and testes have been described, but melanocytic tumors have not been reported...
October 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29031828/non-progressing-cancer-patients-have-persistent-b-cell-responses-expressing-shared-antibody-paratopes-that-target-public-tumor-antigens
#6
Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S Williamson, Xiaomu Chen, Sean M Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B Sokolove, Lawrence Steinman, Tito A Serafini, Guy Cavet, Norman M Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E Emerling, William H Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size...
October 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29024276/large-plaque-type-blue-nevus-with-cellular-nodules-a-rare-unrecognized-melanocytic-tumor
#7
C Baraldi, B Corti, M Lambertini, P A Fanti, A Patrizi, E Dika
A 24-year-old Caucasian woman referred to us due to the modification of a congenital skin lesion in her right scapular area over the past 10 months. Physical examination disclosed multiple blue/whitish nodules arising on a bluish oval plaque, 6 cm in maximum diameter (fig. 1). The patient's personal and family medical history were unremarkable and negative for melanoma and non-melanoma skin cancers. The entire lesion was totally excised. Microscopy revealed a multifocal dermal proliferation of fusiform and dendritic melanocytes arranged in irregular nodules characterized by many individual foci with the histologic appearance of common blue nevus involving the reticular dermis (fig...
October 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29020442/two-photon-photosensitizer-polymer-conjugates-for-combined-cancer-cell-death-induction-and-two-photon-fluorescence-imaging-structure-photodynamic-therapy-efficiency-relationship
#8
Cristina Cepraga, Sophie Marotte, Edna Ben Daoud, Arnaud Favier, Pierre-Henri Lanoe, Cyrille Monnereau, Patrice Baldeck, Chantal Andraud, Jacqueline Marvel, Marie-Therese Charreyre, Yann Leverrier
One of the challenges of photodynamic therapy is to increase the penetration depth of light irradiation in the tumor tissues. Although two-photon excitation strategies have been developed, the two-photon absorption cross-sections of clinically used photosensitizers are generally low (below 300 GM). Besides, photosensitizers with high cross-section values are often non water-soluble. In this research work, a whole family of photosensitizer-polymer conjugates was synthesized via the covalent binding of a photosensitizer with a relatively high cross-section along a biocompatible copolymer chain...
October 11, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#9
K A Gelato, L Schöckel, O Klingbeil, T Rückert, R Lesche, J Toedling, E Kalfon, M Héroult, P Lejeune, U Mönning, A E Fernández-Montalván, S Bäurle, S Siegel, B Haendler
Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28988323/analysis-of-nod-like-receptor-nlrp1-in-multiple-sclerosis-families
#10
Cecily Q Bernales, Mary Encarnacion, Maria G Criscuoli, Irene M Yee, Anthony L Traboulsee, A Dessa Sadovnick, Carles Vilariño-Güell
The implementation of exome sequencing technologies has started to unravel the genetic etiology of familial multiple sclerosis (MS). A homozygote p.G587S mutation in NLRP1 has been suggested as potentially causative for the onset of MS in an affected sibling pair, who later developed malignant melanoma. To validate the proposed role of recessive NLRP1 mutations in the pathological mechanisms of MS, we examined exome sequencing data from 326 MS patients from Canada for the identification of NLRP1 missense and nonsense variants...
October 7, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28986867/genetic-and-functional-analysis-of-grin2a-in-tumor-samples
#11
Todd D Prickett, Jared J Gartner, Yardena Samuels
Ionotropic glutamate receptors (iGluRs) are large integral membrane multi-protein complexes that create ion channels in plasma membranes. Upon binding of receptor specific ligands (e.g., glutamate), increased efflux or influx of mono- or divalent cations (e.g., Ca(2+)) promotes synaptic transmission, cellular migration, and survival. Three classes of iGluRs were originally defined after their respective agonists: AMPA, kainate, and NMDA receptors (NMDARs). Recently, we examined iGluR families at the genetic level using Next-Generation Sequencing (NGS) (whole-exome sequencing (WES)) and discovered a high prevalence of somatic mutations within the gene for one of the NMDAR subunits, GRIN2A, specifically in malignant melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986701/mechano-growth-factor-e-peptide-inhibits-invasion-of-melanoma-cells-and-up-regulates-chop-expression-via-endoplasmic-reticulum-stress
#12
Jianhua He, Lili Dong, Kang Xu, Yuna Qian, Chunli Wang, Yongqiang Sha, Juila Li Zhong, Wanqian Liu, Yonggang Lv, Yang Song, Li Yang
OBJECTIVE: To evaluate the effects of mechano growth factor E peptide (MGF) on the invasive properties of melanoma cells. RESULTS: Melanoma cells (GLL19) were treated with 10, 20 and 30 ng MGF/ml for 24 h. Their invasive properties were investigated by transwell assay. Cytoskeleton reorganization was assessed via staining with phalloidin-FITC; lysyl oxidase (LOX) family gene expression was tested by qRT-PCR, and western blotting was used to detect expression of the matrix metalloproteinases (MMPs) and endoplasmic reticulum (ER) stress...
October 6, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28986450/stap-2-promotes-prostate-cancer-growth-by-enhancing-egfr-stabilization
#13
Yuichi Kitai, Masashi Iwakami, Kodai Saitoh, Sumihito Togi, Serina Isayama, Yuichi Sekine, Ryuta Muromoto, Jun-Ichi Kashiwakura, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda
Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through upregulation of EGFR signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28984472/sanger-institute-series-uncovering-the-genetics-of-cancer-an-interview-with-david-adams
#14
David J Adams
Dr David Adams speaks to Editor of Oncology Central, Jade Parker: Based at Wellcome Trust Sanger Institute as a senior group leader, David Adams uses DNA sequencing of patients and genetic screens in human cells and mice to identify cancer genes and genetic interactions. The Adams group studies the mechanisms of cancer development, particularly skin cancer (melanoma) and colorectal cancer. They sequence DNA from families with a high incidence of cancer and also tumors from patients to understand why some people are at greater risk of tumor development and how cancers evolve...
October 6, 2017: Future Oncology
https://www.readbyqxmd.com/read/28979722/pancreatic-adenosquamous-carcinoma-and-intraductal-papillary-mucinous-neoplasm-in-a-cdkn2a-germline-mutation-carrier
#15
Fernando Martínez de Juan, María Reolid Escribano, Carmen Martínez Lapiedra, Fernanda Maia de Alcantara, María Caballero Soto, Ana Calatrava Fons, Isidro Machado
A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma (ASPC) arising in an intraductal papillar mucinous neoplasm (IPMN)...
September 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28978129/melanoma-antigen-a12-regulates-cell-cycle-via-tumor-suppressor-p21-expression
#16
Teruki Yanagi, Ko Nagai, Hiroshi Shimizu, Shu-Ichi Matsuzawa
Melanoma-associated antigen family A (MAGE-A) is a family of cancer/testis antigens that are expressed in malignant tumors but not in normal tissues other than the testes. MAGE-A12 is a MAGE-A family gene whose tumorigenic function in cancer cells remains unclear. Searches of the Oncomine and NextBio databases revealed that malignant tumors show up-regulation of MAGE-A12 mRNA relative to corresponding normal tissue. In PPC1 primary prostatic carcinoma cells and in HCT116 colorectal cancer cells (wild type and p53-depleted), MAGE-A12 gene knockdown using siRNA or shRNA diminishes cancer cell proliferation as assessed by cellular ATP levels, cell counting, and clonogenic assays...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977882/enhanced-chemosensitization-of-anoikis-resistant-melanoma-cells-through-syndecan-2-upregulation-upon-anchorage-independency
#17
TingTing Tseng, WuChing Uen, JenChih Tseng, ShaoChen Lee
Syndecan family proteins are heparan sulfate proteoglycans, which involved in various cellular activities and associating with metastatic potential and chemosensitivity of tumor cells. Melanoma is one of malignant tumors with poor prognosis upon metastasis. Previously, we had shown that melanoma cells remained survived under cell detachment, which was similar to the initial steps of tumor metastasis. Downregulation of syndecan-1 and upregulation of syndecan-2 in melanoma A375 cells were observed by different suspension conditions...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974924/regulatory-pathway-analysis-of-coat-color-genes-in-mongolian-horses
#18
Bei Li, Xiaolong He, Yiping Zhao, Dongyi Bai, Wunierfu Shiraigo, Qinan Zhao, Dugarjaviin Manglai
BACKGROUND: Studies on the molecular genetics of horse skin pigmentation have typically focused on very few genes and proteins. In this study, we used Illumina sequencing to determine the global gene expression profiles in horses with white-colored coats and those with black-colored coats, with the goal of identifying novel genes that could regulate horse coat color. RESULTS: Genes encoding ribosomal-associated proteins were highly expressed in horse skin. We found a total of 231 unigenes that were differentially expressed between horses with white coats and horses with black coats; 119 were down-regulated, and 112 were up-regulated...
2018: Hereditas
https://www.readbyqxmd.com/read/28963435/carbidopa-is-an-activator-of-aryl-hydrocarbon-receptor-with-potential-for-cancer-therapy
#19
Jiro Ogura, Seiji Miyauchi, Kazumi Shimono, Shengping Yang, Sathisha Gonchigar, Vadivel Ganapathy, Yangzom D Bhutia
Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect...
September 28, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28955754/suppression-of-mage-a10-alters-the-metastatic-phenotype-of-tongue-squamous-cell-carcinoma-cells
#20
Bruna Dos Santos Mendonça, Michelle Agostini, Iara Gonçalves Aquino, Wagner Barbosa Dias, Débora Campanella Bastos, Franklin D Rumjanek
MAGE-A10 is a member of the MAGE protein family (melanoma associated antigen) which is overexpressed in cancer cells. Although MAGE-A10 has been characterized for some time and is generally associated to metastasis its function remains unknown. Here we describe experiments using as models oral squamous cell carcinoma (OSCC) cell lines displaying increasing metastatic potential (LN1 and LN2). These cell lines were transduced with lentivirus particles coding for short hairpin against MAGE-A10 mRNA. Repression of MAGE-A10 expression in LN2 cells altered their morphology and impaired growth of LN1 and LN2 cell lines...
July 2017: Biochemistry and Biophysics Reports
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