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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
#1
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
#2
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
#3
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...
April 27, 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
#4
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...
April 26, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28356500/a-novel-testis-specific-protein-pramey-is-involved-in-spermatogenesis-in-cattle
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27707590/development-and-validation-of-a-noninvasive-2-gene-molecular-assay-for-cutaneous-melanoma
#13
Pedram Gerami, Zuxu Yao, David Polsky, Burkhard Jansen, Klaus Busam, Jonhan Ho, Mary Martini, Laura K Ferris
BACKGROUND: Clinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable. OBJECTIVE: We sought to provide clinicians with such a tool. METHODS: A 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy...
January 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27632898/prame-is-critical-for-breast-cancer-growth-and-metastasis
#14
Zhengwang Sun, Zhipeng Wu, Fenglin Zhang, Qunfeng Guo, Lin Li, Kun Li, Hui Chen, Juan Zhao, Dianwen Song, Quan Huang, Lei Li, Jianru Xiao
Breast cancer is the most common cause of cancer death in women and ranks second among cancer deaths. Metastasis is the main cause of death in breast cancer patients. However, the mechanisms underlying the invasion and metastasis of breast cancer cells remain largely elusive. Here we report that the protein PRAME, a tumor-associated antigen isolated from a melanoma, plays a role in preventing the proliferation and metastasis of breast cancer cells. Knocking down of PRAME promotes breast cancer cell proliferation and inhibits apoptosis...
December 5, 2016: Gene
https://www.readbyqxmd.com/read/27603913/cancer-testis-antigens-expression-regulation-tumor-invasion-and-use-in-immunotherapy-of-cancers
#15
REVIEW
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27544054/safety-and-immunogenicity-of-the-prame-cancer-immunotherapeutic-in-patients-with-resected-non-small-cell-lung-cancer-a-phase-i-dose-escalation%C3%A2-study
#16
Jean-Louis Pujol, Tommaso De Pas, Achim Rittmeyer, Eric Vallières, Bartosz Kubisa, Eugeny Levchenko, Sebastian Wiesemann, Gregory A Masters, Robert Shen, Sergei A Tjulandin, Hans-Stefan Hofmann, Nicolas Vanhoutte, Bruno Salaun, Muriel Debois, Silvija Jarnjak, Pedro Miguel De Sousa Alves, Jamila Louahed, Vincent G Brichard, Frédéric F Lehmann
INTRODUCTION: Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964)...
December 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27519286/gene-expression-of-mage-a3-and-prame-tumor-antigens-and-egfr-mutational-status-in-taiwanese-non-small-cell-lung-cancer-patients
#17
Szu-Hua Pan, Kang-Yi Su, Bart Spiessens, Nicole Kusuma, Nicolas F Delahaye, Olivier Gruselle, Aung Myo, An de Creus, Jamila Louahed, Gee-Cheng Chang, Sung-Liang Yu, Pan-Chyr Yang
AIM: To determine the frequency of expression of the tumor-associated antigens (TAAs) melanoma-associated antigen A3 (MAGE-A3) and preferentially expressed antigen of melanoma (PRAME) and the rate of EGFR mutations in a Taiwanese non-small cell lung cancer (NSCLC) population including only adenocarcinomas and squamous cell carcinomas. Furthermore, to investigate associations between TAA expression and EGFR mutations and to evaluate these TAAs as prognostic markers for overall survival...
August 12, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27505074/analytical-characteristics-of-a-noninvasive-gene-expression-assay-for-pigmented-skin-lesions
#18
Zuxu Yao, Talisha Allen, Margaret Oakley, Carol Samons, Darryl Garrison, Burkhard Jansen
We previously reported clinical performance of a novel noninvasive and quantitative PCR (qPCR)-based molecular diagnostic assay (the pigmented lesion assay; PLA) that differentiates primary cutaneous melanoma from benign pigmented skin lesions through two target gene signatures, LINC00518 (LINC) and preferentially expressed antigen in melanoma (PRAME). This study focuses on analytical characterization of this PLA, including qPCR specificity and sensitivity, optimization of RNA input in qPCR to achieve a desired diagnostic sensitivity and specificity, and analytical performance (repeatability and reproducibility) of this two-gene PLA...
August 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27490939/the-in-vitro-generation-of-multi-tumor-antigen-specific-cytotoxic-t-cell-clones-candidates-for-leukemia-adoptive-immunotherapy-following-allogeneic-stem-cell-transplantation
#19
Yehia S Mohamed, Layla A Bashawri, Chittibabu Vatte, Eman Y Abu-Rish, Cyril Cyrus, Wafaa S Khalaf, Michael J Browning
Adoptive T-cell immunotherapy is a promising approach to manage and maintain relapse-free survival of leukemia patients, especially following allogeneic stem cell transplantation. Post-transplant adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) of the donor origin provide graft-versus-tumor effects, with or without graft-versus-host disease. Myeloid leukemias express immunogenic leukemia associated antigens (LAAs); such as WT-1, PRAME, MAGE, h-TERT and others, most of them are able to induce specific T cell responses whenever associated with the proper co-stimulation...
September 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27486988/epigenetic-reprogramming-and-aberrant-expression-of-prame-are-associated-with-increased-metastatic-risk-in-class-1-and-class-2-uveal-melanomas
#20
Matthew G Field, Michael A Durante, Christina L Decatur, Bercin Tarlan, Kristen M Oelschlager, John F Stone, Jeffim Kuznetsov, Anne M Bowcock, Stefan Kurtenbach, J William Harbour
BACKGROUND: We previously identified PRAME as a biomarker for metastatic risk in Class 1 uveal melanomas. In this study, we sought to define a threshold value for positive PRAME expression (PRAME+) in a large dataset, identify factors associated with PRAME expression, evaluate the prognostic value of PRAME in Class 2 uveal melanomas, and determine whether PRAME expression is associated with aberrant hypomethylation of the PRAME promoter. RESULTS: Among 678 samples analyzed by qPCR, 498 (73...
September 13, 2016: Oncotarget
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