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Melanoma antigene gene

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https://www.readbyqxmd.com/read/28314298/multi-omics-profiling-of-patients-with-melanoma-treated-with-nivolumab-in-project-hope
#1
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
#2
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
#3
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 re-activated 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
#4
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
#5
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
#6
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...
March 2, 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
#7
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 (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 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
#8
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 Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M 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 re-invigorated 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...
March 2, 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
#9
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
https://www.readbyqxmd.com/read/28250926/tumour-cell-conditioned-medium-reveals-greater-m2-skewing-of-macrophages-in-the-absence-of-properdin
#10
Izzat A M Al-Rayahi, Michael J Browning, Cordula Stover
INTRODUCTION: The tumour microenvironment is shaped by the interaction of immune, non immune, and tumour cells present in close proximity. Tumour cells direct the development of a locally immune suppressed state, affecting the activity of anti tumour T cells and preparing the escape phase of tumour development. Macrophages in the tumour typically develop into so-called tumour associated macrophages with a distinct profile of activities which lead to a reduction in inflammation and antigen presentation...
March 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28212574/the-combined-action-of-mast-cell-chymase-tryptase-and-carboxypeptidase-a3-protects-against-melanoma-colonization-of-the-lung
#11
Mirjana Grujic, Aida Paivandy, Ann-Marie Gustafson, Allan R Thomsen, Helena Öhrvik, Gunnar Pejler
Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178658/prime-boost-immunization-by-both-dna-vaccine-and-oncolytic-adenovirus-expressing-gm-csf-and-shrna-of-tgf-%C3%AE-2-induces-anti-tumor-immune-activation
#12
So Young Kim, Dongxu Kang, Hye Jin Choi, Yeonsoo Joo, Joo-Hang Kim, Jae J Song
A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28114254/adoptive-cell-therapy-for-metastatic-melanoma
#13
Efrat Merhavi-Shoham, Orit Itzhaki, Gal Markel, Jacob Schachter, Michal J Besser
Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28105158/time-dependent-transition-of-the-immunoglobulin-g-subclass-and-immunoglobulin-e-response-in-cancer-patients-vaccinated-with-cholesteryl-pullulan-melanoma-antigen-gene-a4-nanogel
#14
Noriaki Kyogoku, Hiroaki Ikeda, Takahiro Tsuchikawa, Takehiro Abiko, Aki Fujiwara, Takehiro Maki, Yoshiyuki Yamamura, Masaomi Ichinokawa, Kimitaka Tanaka, Naoko Imai, Yoshihiro Miyahara, Shinichi Kageyama, Hiroshi Shiku, Satoshi Hirano
A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28043151/identification-of-magea12-as-a-prognostic-outlier-gene-in-gastric-cancers
#15
J Wu, J Wang, W Shen
Melanoma antigen (MAGE) family genes are frequently over-expressed in a subset population of multiple cancers, and serve as idea therapeutic targets; however, their distribution pattern in gastric cancers has not yet been evaluated. In this study, we first performed a cancer outlier profile analysis (COPA) on a series of public gene expression datasets of gastric cancer, and identified MAGEA12 showing a significant outlier expression model reproducibly. We further in silico validated that MAGEA12 outlier over-expression were associated with poor clinical outcome using six microarray datasets from GEO database...
2017: Neoplasma
https://www.readbyqxmd.com/read/28042025/androgen-receptor-regulation-by-histone-methyltransferase-suppressor-of-variegation-3-9-homolog-2-and-melanoma-antigen-a11
#16
Emily B Askew, Suxia Bai, Amanda B Parris, John T Minges, Elizabeth M Wilson
Androgen receptor (AR) transcriptional activity depends on interactions between the AR NH2-terminal region and transcriptional coregulators. A yeast two-hybrid screen of a human testis library using predicted α-helical NH2-terminal fragment AR-(370-420) as bait identified suppressor of variegation 3-9 homolog 2 (SUV39H2) histone methyltransferase as an AR interacting protein. SUV39H2 interaction with AR and the AR coregulator, melanoma antigen-A11 (MAGE-A11), was verified in two-hybrid, in vitro glutathione S-transferase affinity matrix and coimmunoprecipitation assays...
March 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#17
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
https://www.readbyqxmd.com/read/27976415/up-regulation-of-follistatin-like-1-by-the-androgen-receptor-and-melanoma-antigen-a11-in-prostate-cancer
#18
Shifeng Su, Amanda B Parris, Gail Grossman, James L Mohler, Zengjun Wang, Elizabeth M Wilson
BACKGROUND: High affinity androgen binding to the androgen receptor (AR) activates genes required for male sex differentiation and promotes the development and progression of prostate cancer. Human AR transcriptional activity involves interactions with coregulatory proteins that include primate-specific melanoma antigen-A11 (MAGE-A11), a coactivator that increases AR transcriptional activity during prostate cancer progression to castration-resistant/recurrent prostate cancer (CRPC). METHODS: Microarray analysis and quantitative RT-PCR were performed to identify androgen-regulated MAGE-A11-dependent genes in LAPC-4 prostate cancer cells after lentivirus shRNA knockdown of MAGE-A11...
December 14, 2016: Prostate
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#19
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#20
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
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