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Melanoma antigene gene

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
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...
March 5, 2018: Toxicology Letters
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
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
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 TCRalpha and beta cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TILs) 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...
February 23, 2018: Cancer Immunology Research
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
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
Shina Liu, Fei Liu, Weina Huang, Lina Gu, Lingjiao Meng, Yingchao Ju, Yunyan Wu, Juan Li, Lihua Liu, Meixiang Sang
Recently, we have reported that the product of Melanoma Antigens Genes (MAGE) family member MAGE-A11 is an independent poor prognostic marker for esophageal squamous cell carcinoma (ESCC). However, the reason how MAGE-A11 is activated in ESCC progression still remains unclear. In the current study, we demonstrated that DNA methylation and the subsequent histone posttranslational modifications play crucial roles in the regulation of MAGE-A11 in ESCC progression. We found that the methylation rate of TFCP2/ZEB1 binding site on MAGE-A11 promoter in ESCC tissues and cells is higher than the normal esophageal epithelial tissues and cells...
January 9, 2018: Oncotarget
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
Hiroshi Kawamoto, Kyoko Masuda, Seiji Nagano, Takuya Maeda
Recent advances in adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) have led to moderate therapeutic anti-cancer effects in clinical trials. However, a critical issue, namely that CTLs collected from patients are easily exhausted during expansion culture, has yet to be solved. To address this issue, we have been developing a strategy which utilizes induced pluripotent stem cell (iPSC) technology. This strategy is based on the idea that when iPSCs are produced from antigen-specific CTLs, CTLs regenerated from such iPSCs should show the same antigen specificity as the original CTLs...
March 2018: International Journal of Hematology
Nobutaka Nakamura, Takanori Matsui, Yuji Ishibashi, Ami Sotokawauchi, Kei Fukami, Yuichiro Higashimoto, Sho-Ichi Yamagishi
Epidemiological studies have suggested the link between cumulative diabetic exposure and cancer. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) may contribute to the phenomenon. We examined here the effects of DNA aptamer raised against RAGE (RAGE-aptamer) on growth and liver metastasis of G361 melanoma in nude mice. Malignant melanoma cells were intradermally injected into the upper flank region of nude mice, which received continuous administration of RAGE-aptamer (38.4 pmol/day/g body weight) or vehicle intraperitoneally by an osmotic pump up to 42 days...
November 6, 2017: Molecular Medicine
Ernesto Mejías-Pérez, Liliana Carreño-Fuentes, Mariano Esteban
Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options in the fight against cancer. The poxviruses have many features that make them an attractive platform for the development of oncolytic vectors, with some candidates currently in clinical trials. Here, we report the design and generation of a new oncolytic vector based on the vaccinia virus Western Reserve (WR) strain...
March 30, 2018: Molecular Therapy Oncolytics
Joshua R Veatch, Sylvia M Lee, Matthew Fitzgibbon, I-Ting Chow, Brenda Jesernig, Thomas Schmitt, Ying Ying Kong, Julia Kargl, A McGarry Houghton, John A Thompson, Martin McIntosh, William W Kwok, Stanley R Riddell
T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). Tumor exome sequencing surprisingly revealed less than 30 somatic mutations, including oncogenic BRAF V600E...
January 23, 2018: Journal of Clinical Investigation
Yaping N Tu, Wei Lue Tong, John M Yavorski, George Blanck
We developed a scripted algorithm, based on previous, earlier editions of the algorithm, to mine prostate cancer exome files for T-cell receptor (TcR) recombination reads: Reads representing TcR gene recombinations were identified in 497 prostate cancer exome files from the cancer genome atlas (TCGA). As has been reported for melanoma, co-detection of productive TcR-α and TcR-β recombination reads correlated with an RNA expression signature representing T-cell exhaustion, particularly with high RNA levels for PD-1 and PD-L1, in comparison to several different control sets of samples...
January 22, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
Nobue Futawatari, Takashi Fukuyama, Rui Yamamura, Akiko Shida, Yoshihito Takahashi, Yatsushi Nishi, Yoshinobu Ichiki, Noritada Kobayashi, Hitoshi Yamazaki, Masahiko Watanabe
AIM: To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. METHODS: Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained...
December 14, 2017: World Journal of Gastroenterology: WJG
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
Jean-Jacques Grob, Laurent Mortier, Lionel D'Hondt, Florent Grange, Jean Francois Baurain, Brigitte Dréno, Céleste Lebbe, Caroline Robert, Anne Dompmartin, Bart Neyns, Marc Gillet, Jamila Louahed, Silvija Jarnjak, Frédéric F Lehmann
Background: We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. Methods: In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine...
2017: ESMO Open
Yohsuke Yagawa, Mark Robertson-Tessi, Susan L Zhou, Alexander R A Anderson, James J Mulé, Adam W Mailloux
The induction of ectopic lymph node structures (ELNs) holds great promise to augment immunotherapy against multiple cancers including metastatic melanoma, in which ELN formation has been associated with a unique immune-related gene expression signature composed of distinct chemokines. To investigate the therapeutic potential of ELNs induction, preclinical models of ELNs are needed for interrogation of these chemokines. Computational models provide a non-invasive, cost-effective method to investigate leukocyte trafficking in the tumor microenvironment, but parameterizing such models is difficult due to differing assay conditions and contexts among the literature...
November 22, 2017: Scientific Reports
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M Gamero, Jonathan Soboloff, Italo Tempera, M Raza Zaidi
CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner...
November 17, 2017: Cancer Research
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