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https://www.readbyqxmd.com/read/29755733/recent-advancements-in-the-management-of-retinoblastoma-and-uveal-melanoma
#1
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
#2
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/29738081/prame-peptide-specific-cd8-t-cells-represent-the-predominant-response-against-leukemia-associated-antigens-laas-in-healthy-individuals
#3
Sarah Matko, Julia Manderla, Maria Bonsack, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
Antigen-specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia associated antigen (LAA)-specific T cells in HIs still limits such an approach for tumor therapy. Therefore, we have investigated T cell responses against prominent candidates comprising WT1, PRAME, Survivin, NY-ESO and p53 by screening PBMCs from HIs using intracellular IFN-γ staining following provocation with LAA peptide mixes...
May 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29615432/adoptive-immunotherapy-using-prame-specific-t-cells-in-medulloblastoma
#4
Domenico Orlando, Evelina Miele, Biagio De Angelis, Marika Guercio, Iolanda Boffa, Matilde Sinibaldi, Agnese Po, Ignazio Caruana, Luana Abballe, Andrea Carai, Simona Caruso, Antonio Camera, Annemarie Moseley, Renate S Hagedoorn, Mirjam H M Heemskerk, Felice Giangaspero, Angela Mastronuzzi, Elisabetta Ferretti, Franco Locatelli, Concetta Quintarelli
Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 medulloblastoma patients. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy...
April 3, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439259/downregulation-of-prame-suppresses-proliferation-and-promotes-apoptosis-in-hepatocellular-carcinoma-through-the-activation-of-p53-mediated-pathway
#5
Hanzhang Zhu, Jingrui Wang, Junjie Yin, Bei Lu, Qijun Yang, Yafeng Wan, Changku Jia
BACKGROUND/AIMS: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. METHODS: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29407229/combined-analysis-of-dna-methylation-and-gene-expression-profiles-of-osteosarcoma-identified-several-prognosis-signatures
#6
Wen Tian, Yongsheng Li, Jinghua Zhang, Jijun Li, Jinghua Gao
Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While, the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we conducted a combined analysis of two types of microarray datasets (gene expression and DNA methylation) from the Gene Expression Omnibus (GEO). Differential methylation sites (DMS) were identified by the IMA package and differential expression genes (DEGs) were screened out via the limma package...
April 15, 2018: Gene
https://www.readbyqxmd.com/read/29387942/partners-in-crime-neutrophils-and-monocytes-macrophages-in-inflammation-and-disease
#7
REVIEW
Kathryn Prame Kumar, Alyce J Nicholls, Connie H Y Wong
Neutrophils are becoming recognized as highly versatile and sophisticated cells that display de novo synthetic capacity and potentially prolonged lifespan. Emerging concepts such as neutrophil heterogeneity and plasticity have revealed that, under pathological conditions, neutrophils may differentiate into discrete subsets defined by distinct phenotypic and functional characteristics. Indeed, these newly described neutrophil subsets will undoubtedly add to the already complex interactions between neutrophils and other immune cell types for an effective immune response...
March 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29167000/-study-on-genetype-in-lung-squamous-carcinoma-by-high-throughput-of-transcriptome-sequence
#8
Ying Xiong, Mingzhen Li, Panpan Zhang, Liyi Zhang, Yue Yang
BACKGROUND: Recently, there is no effective targeted drug for to the lung squamous carcinoma, the targeted drug for the adenocarcinoma does not benefit for the patients with squamous lung cancer, and researchers have known less targets for this type of patients. The main study herein is to screen and identify the specific key genes for the lung squamous carcinoma that will provide potential novel targets to describe pathogenesis of lung cancer. METHODS: Transcript sequence was used to detect the five pairs lung squamous carcinoma and normal lung tissues and bioinformatics was performed to investigate the differential coding genes between them and quantitative PCR was done to validate the key genes expression in lung cancer cell lines...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29029482/-in-vivo-immuno-targeting-of-an-extracellular-epitope-of-membrane-bound-preferentially-expressed-antigen-in-melanoma-prame
#9
Dmitry Pankov, Ludvig Sjöström, Teja Kalidindi, Sang-Gyu Lee, Kjell Sjöström, Rui Gardner, Michael R McDevitt, Richard O'Reilly, Daniel L J Thorek, Steven M Larson, Darren Veach, David Ulmert
Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is overexpressed in a broad range of malignancies, while absent in most healthy human tissues, making it an attractive diagnostic cancer biomarker and therapeutic target. Although commonly viewed as an intracellular protein, we have demonstrated that PRAME has a membrane bound form with an external epitope targetable with conventional antibodies. We generated a polyclonal antibody (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide sequence of PRAME...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28953414/prame-gene-copy-number-variation-is-related-to-its-expression-in-multiple-myeloma
#10
Lu Yang, Ya-Zhe Wang, Hong-Hu Zhu, Yan Chang, Ling-Di Li, Wen-Min Chen, Ling-Yu Long, Yan-Huan Zhang, Yan-Rong Liu, Jin Lu, Ya-Zhen Qin
Multiple myeloma (MM) patients commonly present abnormal expression of cancer-testis antigens, which may serve as immunotherapeutic targets and prognostic factors. We previously reported that preferentially expressed antigen of melanoma (PRAME) overexpression in bone marrow mononuclear cells is related to progression in MM patients treated with non-bortezomib-containing regimens. The mechanism underlying variations in PRAME expression remains unknown. To investigate the impact of gene copy number variation (CNV) on PRAME expression, plasma cells were sorted from 50 newly diagnosed patients and 8 healthy volunteers to measure PRAME transcript levels and gene copy numbers by real-time quantitative polymerase chain reaction...
September 27, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28951518/immune-activation-in-early-stage-non-small-cell-lung-cancer-patients-receiving-neoadjuvant-chemotherapy-plus-ipilimumab
#11
John S Yi, Neal Ready, Patrick Healy, Chelsae Dumbauld, Robyn Osborne, Mark Berry, Debra Shoemaker, Jeffrey Clarke, Jeffrey Crawford, Betty Tong, David Harpole, Thomas A D'Amico, Frances McSherry, Frank Dunphy, Shannon J McCall, Jared D Christensen, Xiaofei Wang, Kent J Weinhold
Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non-small cell lung cancer (NSCLC) patients. Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles. Results: Chemotherapy alone had little effect on immune parameters in PBMCs...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28862643/a-therapeutic-t-cell-receptor-mimic-antibody-targets-tumor-associated-prame-peptide-hla-i-antigens
#12
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
#13
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...
September 2017: Pathology International
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#14
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...
November 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
#15
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...
September 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#16
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
#17
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
#18
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
#19
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
#20
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
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