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Melanoma antigene gene

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https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#1
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755733/recent-advancements-in-the-management-of-retinoblastoma-and-uveal-melanoma
#2
REVIEW
Amy C Schefler, Ryan S Kim
Retinoblastoma and uveal melanoma are the most common intraocular malignancies observed in pediatric and adult populations, respectively. For retinoblastoma, intra-arterial chemotherapy has dramatically improved treatment outcomes and eye salvage rates compared with traditional salvage rates of systemic chemotherapy and external beam radiation therapy. Intravitreal injections of chemotherapy have also demonstrated excellent efficacy for vitreous seeds. Uveal melanoma, on the other hand, is treated predominantly with iodine-125 plaque brachytherapy or with proton beam therapy...
2018: F1000Research
https://www.readbyqxmd.com/read/29742191/gene-expression-analysis-differentiates-melanomas-from-spitz-nevi
#3
Burkhard Jansen, Doyle Hansen, Ronald Moy, Maesa Hanhan, Zuxu Yao
INTRODUCTION: Pediatric Spitz nevi can pose significant diagnostic challenges to both clinicians and dermatopathologists when the current image-recognition based gold standard is employed. PRAME (preferentially expressed antigen in melanoma) and/or LINC (long intergeneic non-coding RNA 518) gene expression in adult patients in samples obtained non-invasively via adhesive patches differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91%, and a specificity of 69%, to help clinicians rule out melanoma and the need for surgical biopsies of atypial pigmented lesions with suspicion for melanoma...
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29737353/induction-of-necrotic-cell-death-and-activation-of-sting-in-the-tumor-microenvironment-via-cationic-silica-nanoparticles-leading-to-enhanced-antitumor-immunity
#4
Myunggi An, Chunsong Yu, Jingchao Xi, Joyce Reyes, Guangzhao Mao, Wei-Zen Wei, Haipeng Liu
Nanotechnology has demonstrated tremendous clinical utility, with potential applications in cancer immunotherapy. Although nanoparticles with intrinsic cytotoxicity are often considered unsuitable for clinical applications, such toxicity may be harnessed in the fight against cancer. Nanoparticle-associated toxicity can induce acute necrotic cell death, releasing tumor-associated antigens which may be captured by antigen-presenting cells to initiate or amplify tumor immunity. To test this hypothesis, cytotoxic cationic silica nanoparticles (CSiNPs) were directly administered into B16F10 melanoma implanted in C57BL/6 mice...
May 8, 2018: Nanoscale
https://www.readbyqxmd.com/read/29735366/self-delivering-rnai-targeting-pd-1-improves-tumor-specific-t-cell-functionality-for-adoptive-cell-therapy-of-malignant-melanoma
#5
Maarten A Ligtenberg, Yago Pico de Coaña, Taisia Shmushkovich, Yuya Yoshimoto, Iva Truxova, Yuan Yang, Monica Betancur-Boissel, Alexey V Eliseev, Alexey D Wolfson, Rolf Kiessling
Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT...
April 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29720400/interferon-regulatory-factor-1-and-a-variant-of-heterogeneous-nuclear-ribonucleoprotein-l-coordinately-silence-the-gene-for-adhesion-protein-ceacam1
#6
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 in CEACAM1, generating L-iso. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29708315/glypican-3-and-melanoma-antigen-genes-1-and-3-as-tumor-markers-for-hepatocellular-carcinoma
#7
Nadia M El-Wahab, Hebat-Allah G Rashed, Wafaa T El-Sherif, Sohair K Sayed, Mohamed O Abd-Elmalek, Abeer Refaiy, Hussein Fakhry, Abeer A Mokhtar
Hepatocellular carcinoma (HCC) is the commonest liver cancer; its incidence and prevalence are continuously increased. Glypican3 (GPC3), melanoma antigen-1, 3 genes (MAGE1 and 3) are tumor markers used in HCC. We evaluated their role in HCC detection and assessed their relation to tumor parameters. Three groups, HCC group, liver cirrhosis group and a control group were studied. AFP, GPC3, and MAGE1 and 3 mRNA were determined in all study subjects. Tissue GPC3 was examined in patients with HCC only. Serum AFP and GPC3 were elevated in HCC group compared to other groups (P < 0...
June 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29678949/hu-antigen-r-regulates-antiviral-innate-immune-responses-through-the-stabilization-of-mrna-for-polo-like-kinase-2
#8
Takuya Sueyoshi, Takumi Kawasaki, Yuichi Kitai, Daisuke Ori, Shizuo Akira, Taro Kawai
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-κB, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#9
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 6, 2018: Cell
https://www.readbyqxmd.com/read/29628306/tumor-resident-dendritic-cells-and-macrophages-modulate-the-accumulation-of-tcr-engineered-t-cells-in-melanoma
#10
Alastair Hotblack, Angelika Holler, Alice Piapi, Sophie Ward, Hans J Stauss, Clare L Bennett
Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+ cells in CD11c...
March 16, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29617362/a-novel-approach-to-improve-immune-effector-responses-post-transplant-by-restoration-of-ccl21-expression
#11
Heather E Stefanski, Leslie Jonart, Emily Goren, James J Mulé, Bruce R Blazar
Chemotherapy or chemoradiotherapy conditioning regimens required for bone marrow transplantation (BMT) cause significant morbidity and mortality as a result of insufficient immune surveillance mechanisms leading to increased risks of infection and tumor recurrence. Such conditioning causes host stromal cell injury, impairing restoration of the central (thymus) and peripheral (spleen and lymph node) T cell compartments and slow immune reconstitution. The chemokine, CCL21, produced by host stromal cells, recruits T- and B-cells that provide lymphotoxin mediated instructive signals to stromal cells for lymphoid organogenesis...
2018: PloS One
https://www.readbyqxmd.com/read/29574604/evolution-of-melanoma-antigen-a11-magea11-during-primate-phylogeny
#12
Christopher S Willett, Elizabeth M Wilson
Melanoma antigen-A11 (MAGE-A11) is an X-linked and primate-specific steroid hormone receptor transcriptional coregulator and proto-oncogenic protein whose increased expression promotes the growth of prostate cancer. The MAGEA11 gene is expressed at low levels in normal human testis, ovary, and endometrium, and at highest levels in castration-resistant prostate cancer. Annotated genome predictions throughout the surviving primate lineage show that MAGEA11 acquired three 5' coding exons unique within the MAGEA subfamily during the evolution of New World monkeys (NWM), Old World monkeys (OWM), and apes...
March 24, 2018: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29563979/melanoma-antigen-family-a4-protein-produced-by-transgenic-silkworms-induces-antitumor-immune-responses
#13
Yoko Motokawa, Michifumi Kokubo, Nobuo Kuwabara, Ken-Ichiro Tatematsu, Hideki Sezutsu, Hideyuki Takahashi, Koichi Sakakura, Kazuaki Chikamatsu, Shigeki Takeda
Recent clinical trials with the aim of developing tumor antigen (TA)-specific cancer vaccines against a number of malignancies have focused on the identification of TAs presented by tumor cells and recognized by T cells. In the present study, the TA melanoma antigen family A4 (MAGE-A4) protein was produced using a transgenic (TG) silkworm system. Using in vitro stimulation, it was subsequently determined whether MAGE-A4 protein induced MAGE-A4-specific T cells from peripheral blood mononuclear cells of healthy donors...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29528339/cell-based-molecularly-targeted-therapy-targeting-oncoproteins-with-t-cell-receptor-gene-therapy
#14
Christian S Hinrichs
As oncogenes drive carcinogenesis and promote cancer cell survival, they are highly attractive therapeutic targets, and oncogene-targeting small molecules have achieved some clinical success. While many oncogenes are presently considered to be "druggable," tumors often acquire treatment resistance, and patients are rarely cured in response to oncogene-specific treatment. In this issue of the JCI, Veatch and colleagues describe a patient with metastatic acral melanoma who experienced a complete tumor response following infusion of tumor-infiltrating T cells that targeted multiple tumor antigens, including a BRAFV600E driver mutation...
March 12, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29518473/gene-expression-network-regulated-by-dna-methylation-and-microrna-during-microcystin-leucine-arginine-induced-malignant-transformation-in-human-hepatocyte-l02-cells
#15
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
June 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29518100/associations-between-sun-sensitive-pigmentary-genes-and-serum-prostate-specific-antigen-levels
#16
Visalini Nair-Shalliker, Sam Egger, Agata Chrzanowska, Rebecca Mason, Louise Waite, David Le Couteur, Markus J Seibel, David J Handelsman, Robert Cumming, David P Smith, Bruce K Armstrong
BACKGROUND: Melanoma and prostate cancer may share risk factors. This study examined the association between serum PSA levels, which is a risk factor for prostate cancer, and variants in some melanoma-associated pigmentary genes. METHODS: We studied participants, all aged 70+ years, in the Concord Health and Ageing in Men Project who had no history of prostatitis or received treatment for prostate disease (n = 1033). We genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174)...
2018: PloS One
https://www.readbyqxmd.com/read/29515077/-cancer-immunotherapy-using-gene-engineered-t-cells
#17
Shinichi Kageyama
Cancer immunotherapies using gene-engineered T cells comprise adoptive transfer of T-cell receptor (TCR) and chimeric antigen receptor (CAR) gene-transduced T cells. Although CD19-targeting CAR-T cell therapy is the most progressed, wherein B-cell malignancy is treated efficiently, it also induces cytokine release syndrome and neurotoxicity, which frequently leads to serious adverse events. Of note, TCR-T cell therapy has been primarily used to target melanoma, resulting in 30%-50% of tumor responses. In clinical trials that target NY-ESO-1-expressing synovial sarcoma, a high efficacy of 50%-60% has been obtained...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29475880/identification-of-tumoricidal-tcrs-from-tumor-infiltrating-lymphocytes-by-single-cell-analysis
#18
Kiyomi Shitaoka, Hiroshi Hamana, Hiroyuki Kishi, Yoshihiro Hayakawa, Eiji Kobayashi, Kenta Sukegawa, Xiuhong Piao, Fulian Lyu, Takuya Nagata, Daisuke Sugiyama, Hiroyoshi Nishikawa, Atsushi Tanemura, Ichiro Katayama, Mutsunori Murahashi, Yasushi Takamatsu, Kenzaburo Tani, Tatsuhiko Ozawa, Atsushi Muraguchi
T-cell receptor (TCR) gene therapy is a promising next-generation antitumor treatment. We previously developed a single-T-cell analysis protocol that allows the rapid capture of paired TCRα and β cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TIL) of various cancer patients. We found clonally expanded populations of T cells that expressed the same clonotypic TCR in 50% to 70% of CD137+ CD8+ TILs, indicating that they responded to certain antigens in the tumor environment...
April 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29467889/serum-immunoglobulin-e-response-as-a-marker-for-unfavorable-prognosis-following-cholesteryl-pullulan-mage-a4-vaccination
#19
Takehiro Abiko, Takahiro Tsuchikawa, Kengo Miyauchi, Masataka Wada, Noriaki Kyogoku, Toshiaki Shichinohe, Yoshihiro Miyahara, Shinichi Kageyama, Hiroaki Ikeda, Hiroshi Shiku, Satoshi Hirano
Since 2009, a cancer vaccine clinical trial was conducted with melanoma antigen gene-A4 as an immunogenic agent. The levels of IgG1, IgG2 and IgG3, which are known to be Type 1 T helper cell-associated antibodies, and the levels of IgG4 and IgE, which are known to be Type 2 T helper cell-associated antibodies, were measured and used as biomarkers for predicting therapeutic effect. The results of the present study indicated a strong positive correlation between IgG2 and IgG4, with a correlation coefficient of R=0...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29450544/hla-class-i-antigen-expression-in-conjunctival-melanoma-is-not-associated-with-pd-l1-pd-1-status
#20
Jinfeng Cao, Niels J Brouwer, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd G van Duinen, Nadine E de Waard, Bruce R Ksander, Arend Mulder, Frans H J Claas, Mirjam H M Heemskerk, Martine J Jager
Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status...
February 1, 2018: Investigative Ophthalmology & Visual Science
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