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Melanoma antigene gene

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https://www.readbyqxmd.com/read/28438869/correlation-between-expression-of-the-cancer-testis-antigen-kk-lc-1-and-helicobacter-pylori-infection-in-gastric-cancer
#1
Takashi Fukuyama, Nobue Futawatari, Yoshinobu Ichiki, Akiko Shida, Taiga Yamazaki, Yatsushi Nishi, Hiroshi Nonoguchi, Yoshihito Takahashi, Hitoshi Yamazaki, Noritada Kobayashi
BACKGROUND/AIM: Our previous study indicated that Kita-kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer cases. Here, we investigated the relationship between KK-LC-1 expression and Helicobacter pylori infection in Japanese patients with gastric cancer. PATIENTS AND METHODS: We examined CTA expression in 25 surgical gastric cancer specimens and anti-H. pylori IgGs in the serum of each patient. RESULTS: KK-LC-1 was expressed in 80% of tumor samples, markedly higher than melanoma antigen gene (MAGE)-A1, MAGE-A3, MAGE-A4, synovial sarcoma, X breakpoint 4 (SSX4) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1)...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#2
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#3
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28424760/insights-into-local-tumor-microenvironment-immune-factors-associated-with-regression-of-cutaneous-melanoma-metastases-by-mycobacterium-bovis-bacille-calmette-gu%C3%A3-rin
#4
Junbao Yang, Maris S Jones, Romela Irene Ramos, Alfred A Chan, Agnes F Lee, Leland J Foshag, Peter A Sieling, Mark B Faries, Delphine J Lee
Mycobacterium bovis bacille Calmette-Guérin (BCG) is listed as an intralesional (IL) therapeutic option for inoperable stage III in-transit melanoma in the National Comprehensive Cancer Network Guidelines. Although the mechanism is unknown, others have reported up to 50% regression of injected lesions, and 17% regression of uninjected lesions in immunocompetent patients after direct injection of BCG into metastatic melanoma lesions in the skin. BCG and other mycobacteria express ligands capable of stimulating the γ9δ2 T cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#5
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28401488/a-no-stop-mutation-in-mageb4-is-a-possible-cause-of-rare-x-linked-azoospermia-and-oligozoospermia-in-a-consanguineous-turkish-family
#6
Ozlem Okutman, Jean Muller, Valerie Skory, Jean Marie Garnier, Angeline Gaucherot, Yoni Baert, Valérie Lamour, Munevver Serdarogullari, Meral Gultomruk, Albrecht Röpke, Sabine Kliesch, Viviana Herbepin, Isabelle Aknin, Moncef Benkhalifa, Marius Teletin, Emre Bakircioglu, Ellen Goossens, Nicolas Charlet-Berguerand, Mustafa Bahceci, Frank Tüttelmann, STéphane Viville
PURPOSE: The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases. METHODS: We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers identified a mutation in the melanoma antigen family B4 (MAGEB4) gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects...
April 11, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28393253/recombinant-adenovirus-of-sea-and-cd80-genes-driven-by-mmre-and-mouse-tert-promoter-induce-effective-antitumor-immune-responses-against-different-types-of-tumor-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#7
Shao-Yan Si, Jun-Li Liu, Jun-Lian Liu, Bing-Xin Xu, Jian-Zhong Li, Ya-Ya Qin, Shu-Jun Song
Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant and can stimulate T cells bearing certain T-cell receptor β-chain variable regions when bound to major histocompatibility complex II molecules. SEA is widely used in research of antitumor therapy. The low affinity T-cell receptor (TCR) interaction with SEA in the absence of MHC class II antigens is sufficient for the induction of cytotoxicity but requires additional CD28/B7 signaling to result in proliferation of resting T cells. In this study, we constructed recombinant adenovirus (named as Ad-MMRE-mTERT-BIS) carrying membrane-expressing SEA (named as SEAtm) and CD80 driven by Myc-Max response elements (MMRE) and mouse telomerase reverse transcriptase (mTERT) promoter to reduce toxicity and to improve safety and efficiency...
April 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28377094/t-cell-target-antigens-across-major-gynecologic-cancers
#8
REVIEW
Alba Rodriguez-Garcia, Nicholas G Minutolo, John M Robinson, Daniel J Powell
Immunotherapies have achieved remarkable success in treating different forms of cancer including melanoma, non-small cell lung carcinoma, bladder cancer, synovial cell sarcoma, and multiple myeloma using immune checkpoint blockade or gene-engineered T-cells. Although gynecologic cancers have not been historically classified as immunogenic tumors, growing evidence has shown that they are in fact able to elicit endogenous antitumor immune responses suggesting that patients with these cancers may benefit from immunotherapy...
April 2, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28362259/non-coding-cancer-driver-candidates-identified-with-a-sample-and-position-specific-model-of-the-somatic-mutation-rate
#9
Malene Juul, Johanna Bertl, Qianyun Guo, Morten Muhlig Nielsen, Michał Świtnicki, Henrik Hornshøj, Tobias Madsen, Asger Hobolth, Jakob Skou Pedersen
Non-coding mutations may drive cancer development. Statistical detection of non-coding driver regions is challenged by a varying mutation rate and uncertainty of functional impact. Here we develop a statistically-founded non-coding driver-detection method, ncdDetect, which includes sample-specific mutational signatures, long-range mutation rate variation, and position-specific impact measures. Using ncdDetect, we screened non-coding regulatory regions of protein-coding genes across a pan-cancer set of whole-genomes (n=505), which top-ranked known drivers and identified new candidates...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28344884/the-differentiation-and-plasticity-of-tc17-cells-are-regulated-by-ctla-4-mediated-effects-on-stats
#10
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#11
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28314298/multi-omics-profiling-of-patients-with-melanoma-treated-with-nivolumab-in-project-hope
#12
Shusuke Yoshikawa, Yoshio Kiyohara, Masaki Otsuka, Ryota Kondou, Chizu Nonomura, Haruo Miyata, Akira Iizuka, Keiichi Ohshima, Kenichi Urakami, Takeshi Nagashima, Masatoshi Kusuhara, Takashi Sugino, Tohru Mochizuki, Ken Yamaguchi, Yasuto Akiyama
BACKGROUND: Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. MATERIALS AND METHODS: The patients with melanoma comprised of six males and seven females, and their mean age was 68 years...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303311/-immunotherapy-of-cancer-with-checkpoint-inhibitors-not-only-in-malignant-melanoma
#13
A Neubauer
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide...
March 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28300603/a-comprehensive-guide-to-the-mage-family-of-ubiquitin-ligases
#14
REVIEW
Anna K Lee, Patrick Ryan Potts
Melanoma antigen (MAGE) genes are conserved in all eukaryotes and encode for proteins sharing a common MAGE homology domain. Although only a single MAGE gene exists in lower eukaryotes, the MAGE family rapidly expanded in eutherians and consists of more than 50 highly conserved genes in humans. A subset of MAGEs initially garnered interest as cancer biomarkers and immunotherapeutic targets due to their antigenic properties and unique expression pattern that is primary restricted to germ cells and aberrantly reactivated in various cancers...
March 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28280601/minimal-residual-disease-in-melanoma-circulating-melanoma-cells-and-predictive-role-of-mcam-muc18-melcam-cd146
#15
REVIEW
Maria Cristina Rapanotti, Elena Campione, Giulia Spallone, Augusto Orlandi, Sergio Bernardini, Luca Bianchi
Circulating tumour cells (CTCs), identified in numerous cancers including melanoma, are unquestionably considered valuable and useful as diagnostic and prognostic markers. They can be detected at all melanoma stages and may persist long after treatment. A crucial step in metastatic processes is the intravascular invasion of neoplastic cells as circulating melanoma cells (CMCs). Only a small percentage of these released cells are efficient and capable of colonizing with a strong metastatic potential. CMCs' ability to survive in circulation express a variety of genes with continuous changes of signal pathways and proteins to escape immune surveillance...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28265230/electrotransfer-of-plasmid-dna-radiosensitizes-b16f10-tumors-through-activation-of-immune-response
#16
Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa
BACKGROUND: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. MATERIALS AND METHODS: The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation...
March 1, 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28257297/new-concepts-in-the-molecular-understanding-of-uveal-melanoma
#17
REVIEW
David Reichstein
PURPOSE OF REVIEW: Uveal melanoma is the most common primary intraocular malignancy, and its metastases are deadly. Significant work has been done to elucidate the molecular framework that causes uveal melanoma development and metastasis. This review is intended to highlight the most recent breakthroughs in the molecular understanding of uveal melanoma. RECENT FINDINGS: Monosomy of chromosome 3 and class 2 gene-expression profile are well-known indicators of melanoma metastasis...
May 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28256716/assessing-microenvironment-immunogenicity-using-tumor-specimen-exomes-co-detection-of-tcr-%C3%AE-%C3%AE-v-d-j-recombinations-correlates-with-pd-1-expression
#18
Yaping N Tu, Wei Lue Tong, Mohammad D Samy, John M Yavorski, Minjung Kim, George Blanck
T-cell receptor (TcR) recombinations can be recovered from tumor specimen, whole exome sequences (WXS) files. However, it is not yet clear how these recombinations represent lymphocytes or an anti-tumor immune response. Here we report the identification of productive TcR-β recombinations in WXS files representing primary and metastatic melanoma. The recombinations are identifiable in about 20% of the cancer genome atlas melanoma samples. This frequency of detection is lower than the frequency of TcR-α VJ recombinations, consistent with the occurrence of biallelic TcR-α recombinations and possibly consistent with the fact that only one junctional recombination is required for TcR-α whereas two recombinations are required to form a TcR-β gene...
March 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#19
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John V Heymach, Stephen G Swisher, Chantale Bernatchez, Gheath Alatrash, Samir Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these reinvigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28251903/integrated-molecular-analysis-of-tumor-biopsies-on-sequential-ctla-4-and-pd-1-blockade-reveals-markers-of-response-and-resistance
#20
Whijae Roh, Pei-Ling Chen, Alexandre Reuben, Christine N Spencer, Peter A Prieto, John P Miller, Vancheswaran Gopalakrishnan, Feng Wang, Zachary A Cooper, Sangeetha M Reddy, Curtis Gumbs, Latasha Little, Qing Chang, Wei-Shen Chen, Khalida Wani, Mariana Petaccia De Macedo, Eveline Chen, Jacob L Austin-Breneman, Hong Jiang, Jason Roszik, Michael T Tetzlaff, Michael A Davies, Jeffrey E Gershenwald, Hussein Tawbi, Alexander J Lazar, Patrick Hwu, Wen-Jen Hwu, Adi Diab, Isabella C Glitza, Sapna P Patel, Scott E Woodman, Rodabe N Amaria, Victor G Prieto, Jianhua Hu, Padmanee Sharma, James P Allison, Lynda Chin, Jianhua Zhang, Jennifer A Wargo, P Andrew Futreal
Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T cell receptor sequencing and whole-exome sequencing within the same cohort and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade...
March 1, 2017: Science Translational Medicine
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