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Melanoma antigene gene

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https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#1
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28647344/oncogene-expressing-senescent-melanocytes-upregulate-mhc-class-ii-a-candidate-melanoma-suppressor-function
#2
John van Tuyn, Farah Jaber-Hijazi, Douglas MacKenzie, John J Cole, Elizabeth Mann, Jeff S Pawlikowski, Taranjit Singh Rai, David M Nelson, Tony McBryan, Andre Ivanov, Karen Blyth, Hong Wu, Simon Milling, Peter D Adams
On acquisition of an oncogenic mutation, primary human and mouse cells can enter oncogene-induced senescence (OIS). OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28639716/expression-of-the-autoantigen-trim33-tif1%C3%AE-in-skin-and-muscle-of-patients-with-dermatomyositis-is-upregulated-together-with-markers-of-cellular-stress
#3
B Scholtissek, S Ferring-Schmitt, J Maier, J Wenzel
Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively)...
June 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28638445/association-of-mage-a1-6-expression-with-lung-cancer-progression
#4
Eunjue Yi, Ji-Eun Chang, Chosun Leem, Chang-Ho Jeon, Sanghoon Jheon
The melanoma-associated antigen (MAGE) genes are known to be expressed in various kinds of tumors including lung cancer. Although they are studied as targets for immunotherapy and tools for early detection of lung cancer, the correlation between MAGE expression and the prognosis in lung cancer has not been clarified. In this study, we evaluated the relationship between MAGE A1-6 gene expression and the clinical prognosis in lung cancer. Bone marrow aspirations were performed in 60 patients who were diagnosed as lung cancer and underwent lung cancer surgery between 2007 and 2008...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28634046/tumor-antigen-prame-is-up-regulated-by-mzf1-in-cooperation-with-dna-hypomethylation-in-melanoma-cells
#5
Yong-Kyu Lee, Ui-Hyun Park, Eun-Joo Kim, Jin-Taek Hwang, Ji-Cheon Jeong, Soo-Jong Um
Elevated expression of preferentially expressed antigen in melanoma (PRAME) has been implicated in disease progression in a variety of cancers. However, the mechanisms underlying the transcriptional regulation of PRAME remain largely unexplored. Initially, we observed that PRAME was elevated in proportion to the malignant potential of melanoma cells. From the in silico prediction of PRAME gene structure, we identified the putative myeloid zinc finger 1 (MZF1) binding sites, which overlap with a CpG-rich region located in the first intron...
June 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#6
Jason Roszik, Wei-Lien Wang, John A Livingston, Christina L Roland, Vinod Ravi, Cassian Yee, Patrick Hwu, Andrew Futreal, Alexander J Lazar, Shreyaskumar R Patel, Anthony P Conley
BACKGROUND: PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma. METHODS: To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28626083/cellular-and-disease-functions-of-the-prader-willi-syndrome-gene-magel2
#7
REVIEW
Klementina Fon Tacer, Patrick Ryan Potts
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme...
June 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#8
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28596641/gene-electrotransfer-of-plasmid-encoding-il-12-recruits-the-m1-macrophages-and-antigen-presenting-cells-inducing-the-eradication-of-aggressive-b16f10-murine-melanoma
#9
Ursa Lampreht Tratar, Luisa Loiacono, Maja Cemazar, Urska Kamensek, Vito Michele Fazio, Gregor Sersa, Emanuela Signori
Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12) in mice bearing aggressive B16F10 murine melanoma...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28589078/recent-clinical-trials-of-cancer-immunogene-therapy-in-companion-animals
#10
REVIEW
Liliana M E Finocchiaro, Gerardo C Glikin
This mini-review presents the results of veterinary clinical trials on immunogene therapy published from 2014 to 2016. A variety of tumors, among them melanoma (canine and equine), mastocytoma (canine), mammary adenocarcinoma (canine) and fibrosarcoma (feline) were treated by using diverse strategies. Non-viral vectors were usually employed to transfer genes of cytokines, suicide enzymes and/or tumor associated antigens. In general terms, minor or no adverse collateral effects were related to these procedures, and treated patients frequently improved their conditions (better quality of life, delayed or suppressed recurrence or metastatic spread, increased survival)...
May 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28573821/overexpression-of-the-human-antigen-r-suppresses-the-immediate-paradoxical-proliferation-of-melanoma-cell-subpopulations-in-response-to-suboptimal-braf-inhibition
#11
Marylise Fernandez, Hedwig Sutterlüty-Fall, Christoph Schwärzler, Sylvain Lemeille, Wolf-Henning Boehncke, Rastine Merat
Tumor plasticity and the heterogeneous response of melanoma cells to targeted therapies are major limits for the long-term efficacy of this line of therapy. Targeting tumor plasticity is theoretically possible through the modulation of the expression of RNA-binding proteins which can affect many different compensatory mechanisms of the adaptive response of malignant cells to targeted therapies. Human antigen R (HuR) is a modulator of gene expression and a transacting factor in the mRNA-processing machinery used in the cell stress response, and is a potential target for reducing tumor plasticity...
June 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28573185/hcv-t-cell-receptor-chain-modifications-to-enhance-expression-pairing-and-antigen-recognition-in-t-cells-for-adoptive-transfer
#12
Kendra C Foley, Timothy T Spear, David C Murray, Kaoru Nagato, Elizabeth Garrett-Mayer, Michael I Nishimura
T cell receptor (TCR)-gene-modified T cells for adoptive cell transfer can mediate objective clinical responses in melanoma and other malignancies. When introducing a second TCR, mispairing between the endogenous and introduced α and β TCR chains limits expression of the introduced TCR, which can result in impaired efficacy or off-target reactivity and autoimmunity. One approach to promote proper TCR chain pairing involves modifications of the introduced TCR genes: introducing a disulfide bridge, substituting murine for human constant regions, codon optimization, TCR chain leucine zipper fusions, and a single-chain TCR...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28561041/acquired-ifn%C3%AE-resistance-impairs-anti-tumor-immunity-and-gives-rise-to-t-cell-resistant-melanoma-lesions
#13
Antje Sucker, Fang Zhao, Natalia Pieper, Christina Heeke, Raffaela Maltaner, Nadine Stadtler, Birgit Real, Nicola Bielefeld, Sebastian Howe, Benjamin Weide, Ralf Gutzmer, Jochen Utikal, Carmen Loquai, Helen Gogas, Ludger Klein-Hitpass, Michael Zeschnigk, Astrid M Westendorf, Mirko Trilling, Susanne Horn, Bastian Schilling, Dirk Schadendorf, Klaus G Griewank, Annette Paschen
Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8(+) T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28560754/oncostatin-m-induces-rig-i-and-mda5-expression-and-enhances-the-double-stranded-rna-response-in-fibroblasts
#14
Sabine Hergovits, Christine Mais, Claude Haan, Ana P Costa-Pereira, Heike M Hermanns
Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts...
May 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28549093/autoantibodies-in-melanoma-associated-retinopathy-recognize-an-epitope-conserved-between-trpm1-and-trpm3
#15
Robert M Duvoisin, Tammie L Haley, Gaoying Ren, Iwona Strycharska-Orczyk, James P Bonaparte, Catherine W Morgans
Purpose: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with malignant melanoma and the presence of anti-retinal autoantibodies, including autoantibodies against transient receptor potential melanopsin 1 (TRPM1), a cation channel expressed by both melanocytes and retinal bipolar cells. The goal of this study was to further map the antigenic epitope. Methods: Patient sera were tested by immunofluorescence and Western blotting on HEK293 cells transfected with enhanced green fluorescent protein (EGFP)-TRPM1 fusion constructs and mouse retina sections...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28542476/functional-interaction-between-co-expressed-mage-a-proteins
#16
Julieta E Laiseca, María F Ladelfa, Javier Cotignola, Leticia Y Peche, Franco A Pascucci, Bryan A Castaño, Mario D Galigniana, Claudio Schneider, Martin Monte
MAGE-A (Melanoma Antigen Genes-A) are tumor-associated proteins with expression in a broad spectrum of human tumors and normal germ cells. MAGE-A gene expression and function are being increasingly investigated to better understand the mechanisms by which MAGE proteins collaborate in tumorigenesis and whether their detection could be useful for disease prognosis purposes. Alterations in epigenetic mechanisms involved in MAGE gene silencing cause their frequent co-expression in tumor cells. Here, we have analyzed the effect of MAGE-A gene co-expression and our results suggest that MageA6 can potentiate the androgen receptor (AR) co-activation function of MageA11...
2017: PloS One
https://www.readbyqxmd.com/read/28542406/human-igg3-with-extended-half-life-does-not-improve-fc-gamma-receptor-mediated-cancer-antibody-therapies-in-mice
#17
Rens Braster, Simran Grewal, Remco Visser, Helga K Einarsdottir, Marjolein van Egmond, Gestur Vidarsson, Marijn Bögels
BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models...
2017: PloS One
https://www.readbyqxmd.com/read/28536262/in-silico-and-cell-based-analyses-reveal-strong-divergence-between-prediction-and-observation-of-t-cell-recognized-tumor-antigen-t-cell-epitopes
#18
Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic, Julia Karbach, George Coukos, Immanuel Luescher
Tumor exomes provide comprehensive information on mutated, over-expressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T cell epitopes, because neoepitope specific T cells often are tumoricidal. However, identifying tumor-specific T cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen binding peptides by in silico algorithms, but the predictive power of this approach is unclear...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28516231/molecular-evolution-of-type-ii-mage-genes-from-ancestral-maged2-gene-and-their-phylogenetic-resolution-of-basal-mammalian-clades
#19
Marcos De Donato, Sunday O Peters, Tanveer Hussain, Hectorina Rodulfo, Bolaji N Thomas, Masroor E Babar, Ikhide G Imumorin
Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen proteins found in various locations in the genome and expressed in normal tissues, thus are not related to cancer as the type I MAGE genes. This gene family exists as a single copy in non-mammals and monotremata, but found as two copies in metatherians and occur as a diverse group in all eutherians. Our studies suggest MAGED2 as the ancestor of this subfamily and the most likely evolutionary history of eutherian type II MAGE genes is hereby proposed based on synteny conservation, phylogenetic relations, genome location, homology conservation, and the protein and gene structures...
May 17, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28498455/overexpression-of-magea2-has-a-prognostic-significance-and-is-a-potential-therapeutic-target-for-patients-with-lung-cancer
#20
Hideki Ujiie, Tatsuya Kato, Daiyoon Lee, Hsin-Pei Hu, Kosuke Fujino, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Kazuhiro Yasufuku
Melanoma-associated antigens (MAGE) are expressed in different type of cancers including lung cancer and have been shown to be functionally related to p53 tumor suppressor gene. Little is known about the relationship between MAGE genes and p53 aberrant expression in lung cancer. The aims of this study were to observe the expression of MAGEA2, examine the role of MAGEA2 in lung cancer survival, investigate its correlation between MAGEA2 and p53, and explore its clinicopathologic significance as a prognostic marker...
May 5, 2017: International Journal of Oncology
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