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https://www.readbyqxmd.com/read/28862643/a-therapeutic-t-cell-receptor-mimic-antibody-targets-tumor-associated-prame-peptide-hla-i-antigens
#1
Aaron Y Chang, Tao Dao, Ron S Gejman, Casey A Jarvis, Andrew Scott, Leonid Dubrovsky, Melissa D Mathias, Tatyana Korontsvit, Victoriya Zakhaleva, Michael Curcio, Ronald C Hendrickson, Cheng Liu, David A Scheinberg
No abstract text is available yet for this article.
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28759137/soft-tissue-sarcomas-from-a-morphological-to-a-molecular-biological-approach
#2
REVIEW
Yoshinao Oda, Hidetaka Yamamoto, Kenichi Kohashi, Yuichi Yamada, Kunio Iura, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki
Recently developed molecular genetic techniques have led to the elucidation of tumor-specific genomic alterations and thereby the reclassification of tumor entities of soft tissue sarcoma. A solitary fibrous tumor-mimicking tumor with the AHRR-NCOA2 gene has been isolated as angiofibroma of soft tissue. As for small round cell sarcomas, novel fusion genes such as CIC-DUX4 and BCOR-CCNB3 have been identified in these tumor groups. SMARCB1/INI1 deficient tumors with round cell morphology are also expected to be reclassified in three types, based on the combination of their morphology and genotype...
July 31, 2017: Pathology International
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#3
Huimeng Lei, Zhangming Yan, Xiaohong Sun, Yue Zhang, Jianhong Wang, Caihong Ma, Qunyuan Xu, Rui Wang, Erich D Jarvis, Zhirong Sun
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data...
July 7, 2017: Brain and Language
https://www.readbyqxmd.com/read/28634046/tumor-antigen-prame-is-up-regulated-by-mzf1-in-cooperation-with-dna-hypomethylation-in-melanoma-cells
#4
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
#5
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/28628042/a-therapeutic-t-cell-receptor-mimic-antibody-targets-tumor-associated-prame-peptide-hla-i-antigens
#6
Aaron Y Chang, Tao Dao, Ron S Gejman, Casey A Jarvis, Andrew Scott, Leonid Dubrovsky, Melissa D Mathias, Tatyana Korontsvit, Victoriya Zakhaleva, Michael Curcio, Ronald C Hendrickson, Cheng Liu, David A Scheinberg
Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that is expressed in many cancers and leukemias. In healthy tissue, PRAME expression is limited to the testes and ovaries, making it a highly attractive cancer target. PRAME is an intracellular protein that cannot currently be drugged. After proteasomal processing, the PRAME300-309 peptide ALYVDSLFFL (ALY) is presented in the context of human leukocyte antigen HLA-A*02:01 molecules for recognition by the T cell receptor (TCR) of cytotoxic T cells...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28611979/impact-of-preferentially-expressed-antigen-of-melanoma-on-the-prognosis-of-hepatocellular-carcinoma
#7
Kenji Oyama, Keita Kanki, Hiroki Shimizu, Yohei Kono, Junya Azumi, Kan Toriguchi, Etsuro Hatano, Goshi Shiota
BACKGROUND: Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. METHODS: PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection...
March 2017: Gastrointestinal Tumors
https://www.readbyqxmd.com/read/28604677/pramel7-mediates-ground-state-pluripotency-through-proteasomal-epigenetic-combined-pathways
#8
Urs Graf, Elisa A Casanova, Sarah Wyck, Damian Dalcher, Marco Gatti, Eva Vollenweider, Michal J Okoniewski, Fabienne A Weber, Sameera S Patel, Marc W Schmid, Jiwen Li, Jafar Sharif, Guido A Wanner, Haruhiko Koseki, Jiemin Wong, Pawel Pelczar, Lorenza Penengo, Raffaella Santoro, Paolo Cinelli
Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance...
July 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#9
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28454473/methylation-pattern-of-preferentially-expressed-antigen-of-melanoma-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#10
Ya-Zhen Qin, Yan-Huan Zhang, Xiao-Ying Qin, Hong-Hu Zhu
Preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is overexpressed in a variety of hematologic malignancies with a great variation in expression. The majority of patients with acute myeloid leukemia (AML) 1-eight-twenty one (ETO)(+) AML and a certain number of myelodysplastic syndromes (MDS) have an abnormally high increase in PRAME expression level. The landscape of PRAME methylation requires evaluation in order to determine the most relevant sites and the exact association of its methylation with expression level and type of disease...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448663/prame-as-a-potential-target-for-immunotherapy-in-metastatic-uveal-melanoma
#11
Gülçin Gezgin, Sietse J Luk, Jinfeng Cao, Mehmet Dogrusöz, Dirk M van der Steen, Renate S Hagedoorn, Daniëlle Krijgsman, Pieter A van der Velden, Matthew G Field, Gregorius P M Luyten, Karoly Szuhai, J William Harbour, Ekaterina S Jordanova, Mirjam H M Heemskerk, Martine J Jager
Importance: Uveal melanoma (UM) is an intraocular primary malignant neoplasm that often gives rise to metastatic disease for which there are no effective therapies. A substantial proportion of UMs express the cancer-testis antigen PRAME (preferentially expressed antigen in melanoma), which can potentially be targeted by adoptive T-cell therapy. Objective: To determine whether there may be a rationale for PRAME-directed T-cell therapy for metastatic UM. Design, Setting, and Participants: An experimental study using a retrospective cohort of 64 patients with UM (median follow-up, 62 months) was conducted from January 8, 2015, to November 20, 2016, at the Leiden University Medical Center...
June 1, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28445578/utility-of-a-noninvasive-2-gene-molecular-assay-for-cutaneous-melanoma-and-effect-on-the-decision-to-biopsy
#12
Laura K Ferris, Burkhard Jansen, Jonhan Ho, Klaus J Busam, Kenneth Gross, Doyle D Hansen, John P Alsobrook, Zuxu Yao, Gary L Peck, Pedram Gerami
Importance: Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated. Objective: To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions...
July 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28356500/a-novel-testis-specific-protein-pramey-is-involved-in-spermatogenesis-in-cattle
#13
Wan-Sheng Liu, Yaqi Zhao, Chen Lu, Gang Ning, Yun Ma, Francisco Diaz, Michael O'Connor
PRAME is a cancer/testis antigen that is predominantly expressed in normal testicular tissues and a variety of tumors. The function of the PRAME family in spermatogenesis remains unknown. This study was designed to characterize the Y-linked PRAME (PRAMEY) protein during spermatogenesis in cattle. We found that PRAMEY is a novel male germ cell-specific, and a germinal granule-associated protein that is expressed in spermatogenic cells during spermatogenesis. The intact PRAMEY protein (58 kDa) was detected in different ages of testes but not in epididymal spermatozoa...
March 29, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28257297/new-concepts-in-the-molecular-understanding-of-uveal-melanoma
#14
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/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-and-decreased-pd-1-and-immune-suppressors
#15
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n = 8), MMR (BCR-ABL1 ≤0.1%, n = 20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n = 16), and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n = 13)...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/27993576/cancer-testis-antigen-expression-in-synovial-sarcoma-ny-eso-1-prame-magea4-and-magea1
#16
Kunio Iura, Akira Maekawa, Kenichi Kohashi, Takeaki Ishii, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, Hidetaka Yamamoto, Katsumi Harimaya, Yukihide Iwamoto, Yoshinao Oda
Synovial sarcoma (SS) is regarded as a relatively chemosensitive sarcoma, but the prognosis of advanced SSs remains poor. Here we identified highly expressed cancer-testis antigens that could be promising immunotherapy targets for SS, using a previously conducted cDNA microarray, and we assessed the clinicopathological or prognostic relationships of these antigens in SS. We compared the gene expression profiles of 11 SSs with those of 3 normal adipose tissues. Among the up-regulated cancer-testis antigens, we analyzed PRAME, MAGEA1, and MAGEA4 and another cancer-testis antigen (NY-ESO-1) together, by immunohistochemistry and real-time polymerase chain reaction in 108 SSs...
March 2017: Human Pathology
https://www.readbyqxmd.com/read/27875783/prame-overexpression-predicted-good-outcome-in-pediatric-b-cell-acute-lymphoblastic-leukemia-patients-receiving-chemotherapy
#17
Yan-Huan Zhang, Ai-Dong Lu, Lu Yang, Ling-Di Li, Wen-Min Chen, Ling-Yu Long, Le-Ping Zhang, Ya-Zhen Qin
To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5...
January 2017: Leukemia Research
https://www.readbyqxmd.com/read/27843625/safety-and-immunogenicity-of-the-prame-cancer-immunotherapeutic-in-metastatic-melanoma-results-of-a-phase-i-dose-escalation-study
#18
R Gutzmer, L Rivoltini, E Levchenko, A Testori, J Utikal, P A Ascierto, L Demidov, J J Grob, R Ridolfi, D Schadendorf, P Queirolo, A Santoro, C Loquai, B Dreno, A Hauschild, E Schultz, T P Lesimple, N Vanhoutte, B Salaun, M Gillet, S Jarnjak, P M De Sousa Alves, J Louahed, V G Brichard, F F Lehmann
PURPOSE: The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. PATIENTS AND METHODS: Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic...
2016: ESMO Open
https://www.readbyqxmd.com/read/27794402/the-prevalence-of-expression-of-mage-a3-and-prame-tumor-antigens-in-east-and-south-east-asian-non-small-cell-lung-cancer-patients
#19
Sumitra Thongprasert, Pan-Chyr Yang, Jung Shin Lee, Ross Soo, Olivier Gruselle, Aung Myo, Jamila Louahed, Frédéric F Lehmann, Vincent G Brichard, Thierry Coche
INTRODUCTION: Treatment of non-small cell lung cancer (NSCLC) is an important and often unmet medical need regardless of the disease stage at the time of first diagnosis. Antigen-specific immunotherapy may be a feasible therapeutic option if tumor associated antigens (TAAs) that can be targeted by the patient's immune system are identified. The study objective (NCT01837511) was to investigate the expression rates of MAGE-A3 and PRAME in tumors from East Asian NSCLC patients, and the associations between TAA expression and clinico-pathologic patient characteristics...
November 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27776018/inhibitor-of-vasculogenic-mimicry-restores-sensitivity-of-resistant-melanoma-cells-to-dna-damaging-agents
#20
Amalia Vartanian, Maria Baryshnikova, Olga Burova, Dariya Afanasyeva, Vsevolod Misyurin, Alexander Belyаvsky, Zoya Shprakh
The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug...
February 2017: Melanoma Research
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