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https://www.readbyqxmd.com/read/28796899/plag1-immunohistochemistry-is-a-sensitive-marker-for-pleomorphic-adenoma-a-comparative-study-with-plag1-genetic-abnormalities
#1
Nora Katabi, Bin Xu, Achim A Jungbluth, Lei Zhang, Sung Yun Shao, Jason Lane, Ronald Ghossein, Cristina R Antonescu
AIMS: PLAG1 gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex-PA) can mimic various benign and malignant salivary gland tumors. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex-PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in situ hybridization (FISH)...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28794017/differential-recruitment-of-e3-ubiquitin-ligase-complexes-regulates-ret-isoform-internalization
#2
Brandy D Hyndman, Mathieu J F Crupi, Susan Peng, Leslie N Bone, Aisha N Rekab, Eric Y Lian, Simona M Wagner, Costin N Antonescu, Lois M Mulligan
The RET receptor tyrosine kinase is implicated in normal development and cancer. RET is expressed as two isoforms, RET9 and RET51, with unique C-terminal tail sequences that recruit distinct protein complexes to mediate signals. Upon activation, RET isoforms are internalized with distinct kinetics, suggesting differences in regulation. Here, we demonstrate that RET9 and RET51 differ in their abilities to recruit E3-ubiquitin ligases to their unique C-termini. RET51, but not RET9, interacts with, and is ubiquitinated by CBL, which is recruited through interactions with the GRB2 adaptor protein...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28791645/measurement-of-epidermal-growth-factor-receptor-derived-signals-within-plasma-membrane-clathrin-structures
#3
Stefanie Lucarelli, Ralph Christian Delos Santos, Costin N Antonescu
The epidermal growth factor (EGF) receptor (EGFR) is an important regulator of cell growth, proliferation, survival, migration, and metabolism. EGF binding to EGFR triggers the activation of the receptor's intrinsic kinase activity, in turn eliciting the recruitment of many secondary signaling proteins and activation of downstream signals, such as the activation of phosphatidylinositol-3-kinase (PI3K) and Akt, a process requiring the phosphorylation of Gab1. While the identity of many signals that can be activated by EGFR has been revealed, how the spatiotemporal organization of EGFR signaling within cells controls receptor outcome remains poorly understood...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28762137/a-clinicopathologic-study-of-head-and-neck-malignant-peripheral-nerve-sheath-tumors
#4
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Ping Chi, Cristina R Antonescu
Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST...
July 31, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28694018/the-enu-3-protein-family-members-function-in-the-wnt-pathway-parallel-to-unc-6-netrin-to-promote-motor-neuron-axon-outgrowth-in-c-elegans
#5
Roxana Oriana Florica, Victoria Hipolito, Stephen Bautista, Homa Anvari, Chloe Rapp, Suzan El-Rass, Alimohammad Asgharian, Costin N Antonescu, Marie T Killeen
The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5...
July 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28692601/recurrent-braf-gene-rearrangements-in-myxoinflammatory-fibroblastic-sarcomas-but-not-hemosiderotic-fibrolipomatous-tumors
#6
Yu-Chien Kao, Valentina Ranucci, Lei Zhang, Yun-Shao Sung, Edward A Athanasian, David Swanson, Brendan C Dickson, Cristina R Antonescu
Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade soft tissue sarcoma with a predilection for acral sites, being associated with a high rate of local recurrence but very infrequent distant metastases. Although a t(1;10) translocation resulting in TGFBR3-MGEA5 fusion has been reported as a recurrent genetic event in MIFS, this abnormality is seen only in a subset of cases. As no studies to date have investigated the spectrum of alternative genetic alterations in TGFBR3-MGEA5 fusion negative MIFS, we undertook a genetic analysis of this particular cohort for further molecular classification...
July 7, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28644513/benign-vascular-lesions-of-the-breast-diagnosed-by-core-needle-biopsy-do-not-require-excision
#7
Christopher Sebastiano, Lucas Gennaro, Edi Brogi, Elizabeth Morris, Zenica L Bowser, Cristina R Antonescu, Fresia Pareja, Sandra Brennan, Melissa P Murray
AIMS: Surgical excision of all benign vascular lesions of the breast identified by core needle biopsy has been recommended in the past to rule out a more serious lesion. In this study we investigated the clinical, radiologic, and pathologic findings in patients diagnosed with a benign vascular lesion at our institution to assess whether excision may be spared for lesions without atypia. METHODS AND RESULTS: We searched the electronic medical record for patients with a vascular lesion of the breast diagnosed between 2000 and 2015...
June 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28621321/bcor-is-a-robust-diagnostic-immunohistochemical-marker-of-genetically-diverse-high-grade-endometrial-stromal-sarcoma-including-tumors-exhibiting-variant-morphology
#8
Sarah Chiang, Cheng-Han Lee, Colin J R Stewart, Esther Oliva, Lien N Hoang, Rola H Ali, Martee L Hensley, Javier A Arias-Stella, Denise Frosina, Achim A Jungbluth, Ryma Benayed, Marc Ladanyi, Meera Hameed, Lu Wang, Yu-Chien Kao, Cristina R Antonescu, Robert A Soslow
Recognition of high-grade endometrial stromal sarcoma is important because of its aggressive clinical behavior. Morphologic features of YWHAE-NUTM2 high-grade endometrial stromal sarcoma may overlap with other uterine sarcoma types. BCOR immunoexpression was studied in these tumors and their morphologic mimics to assess its diagnostic utility. BCOR immunohistochemical staining was performed on archival tissue from 28 high-grade endometrial stromal sarcomas with classic morphology (20 YWHAE-NUTM2, 5 ZC3H7B-BCOR, 3 BCOR-ZC3H7B), 3 high-grade endometrial stromal sarcomas with unusual morphology and unknown gene rearrangement status, 66 low-grade endometrial stromal sarcomas, 21 endometrial stromal nodules, 38 uterine leiomyosarcomas, and 19 uterine leiomyomas...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#9
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28574194/the-big-and-intricate-dreams-of-little-organelles-embracing-complexity-in-the-study-of-membrane-traffic
#10
REVIEW
Allen P Liu, Roberto J Botelho, Costin N Antonescu
Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale and nonlinear regulatory networks...
June 2, 2017: Traffic
https://www.readbyqxmd.com/read/28551330/histopathologic-evaluation-of-atypical-neurofibromatous-tumors-and-their-transformation-into-malignant-peripheral-nerve-sheath-tumor-in-neurofibromatosis-1-patients-a-consensus-overview
#11
Markku M Miettinen, Cristina R Antonescu, Christopher D M Fletcher, Aerang Kim, Alexander J Lazar, Martha M Quezado, Karlyne M Reilly, Anat Stemmer-Rachamimov, Douglas R Stewart, David Viskochil, Brigitte Widemann, Arie Perry
Neurofibromatosis 1 (NF1) patients develop multiple neurofibromas, with 8-15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, following a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant trans-formation of neurofibromas. Nuclear atypia alone is generally insignificant...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28539323/etv1-positive-cells-give-rise-to-braf-v600e-mutant-gastrointestinal-stromal-tumors
#12
Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R Antonescu, Yu Chen, Ping Chi
Gastrointestinal stromal tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA wild-type GIST, including mutant BRAF-driven tumors, has been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here, we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28521780/ultrasound-and-microbubble-induced-release-from-intracellular-compartments
#13
Farah Hussein, Costin Antonescu, Raffi Karshafian
BACKGROUND: Ultrasound and microbubbles (USMB) have been shown to enhance the intracellular uptake of molecules, generally thought to occur as a result of sonoporation. The underlying mechanism associated with USMB-enhanced intracellular uptake such as membrane disruption and endocytosis may also be associated with USMB-induced release of cellular materials to the extracellular milieu. This study investigates USMB effects on the molecular release from cells through membrane-disruption and exocytosis...
May 18, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28510278/tfg-met-fusion-in-an-infantile-spindle-cell-sarcoma-with-neural-features
#14
Uta Flucke, Max M van Noesel, Marc Wijnen, Lei Zhang, Chun-Liang Chen, Yun-Shao Sung, Cristina R Antonescu
An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression...
September 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28505004/a-subset-of-malignant-mesotheliomas-in-young-adults-are-associated-with-recurrent-ewsr1-fus-atf1-fusions
#15
Patrice Desmeules, Philippe Joubert, Lei Zhang, Hikmat A Al-Ahmadie, Christopher D Fletcher, Efsevia Vakiani, Deborah F Delair, Natasha Rekhtman, Marc Ladanyi, William D Travis, Cristina R Antonescu
Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28504702/pgbd5-promotes-site-specific-oncogenic-mutations-in-human-tumors
#16
Anton G Henssen, Richard Koche, Jiali Zhuang, Eileen Jiang, Casie Reed, Amy Eisenberg, Eric Still, Ian C MacArthur, Elias Rodríguez-Fos, Santiago Gonzalez, Montserrat Puiggròs, Andrew N Blackford, Christopher E Mason, Elisa de Stanchina, Mithat Gönen, Anne-Katrin Emde, Minita Shah, Kanika Arora, Catherine Reeves, Nicholas D Socci, Elizabeth Perlman, Cristina R Antonescu, Charles W M Roberts, Hanno Steen, Elizabeth Mullen, Stephen P Jackson, David Torrents, Zhiping Weng, Scott A Armstrong, Alex Kentsis
Genomic rearrangements are a hallmark of human cancers. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as encoding an active DNA transposase expressed in the majority of childhood solid tumors, including lethal rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found previously undefined genomic rearrangements in human rhabdoid tumors. These rearrangements involved PGBD5-specific signal (PSS) sequences at their breakpoints and recurrently inactivated tumor-suppressor genes...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28449608/primary-pulmonary-myxoid-sarcoma-a-newly-described-entity-report-of-a-case-and-review-of-the-literature
#17
Carlos N Prieto-Granada, Rose B Ganim, Lei Zhang, Cristina Antonescu, James Mueller
Primary pulmonary myxoid sarcoma (PPMS) is a recently described, exceedingly rare low-grade lung sarcoma that tends to present in young females as an endobronchial mass and shows evidence of an EWSR1- CREB1 fusion. Herein, we present a case of PPMS with fluorescence in situ hybridization (FISH) analysis for EWSR1 and CREB1 rearrangements. An 80-year-old woman presented with an endobronchial, multinodular tumor exhibiting spindle, ovoid and epithelioid cells arranged in reticular/lattice-like and alveolar-like patterns in a myxoid background...
April 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28448384/cytoreductive-surgery-for-metastatic-gastrointestinal-stromal-tumors-treated-with-tyrosine-kinase-inhibitors-a-2-institutional-analysis
#18
Mark Fairweather, Vinod P Balachandran, George Z Li, Monica M Bertagnolli, Cristina Antonescu, William Tap, Samuel Singer, Ronald P DeMatteo, Chandrajit P Raut
OBJECTIVE: To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery. BACKGROUND: Early reports suggested that patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts. METHODS: Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined...
April 26, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#19
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). However, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here, we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
June 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28346326/sarcomas-with-cic-rearrangements-are-a-distinct-pathologic-entity-with-aggressive-outcome-a-clinicopathologic-and-molecular-study-of-115-cases
#20
Cristina R Antonescu, Adepitan A Owosho, Lei Zhang, Sonja Chen, Kemal Deniz, Joseph M Huryn, Yu-Chien Kao, Shih-Chiang Huang, Samuel Singer, William Tap, Inga-Marie Schaefer, Christopher D Fletcher
CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available...
July 2017: American Journal of Surgical Pathology
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