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https://www.readbyqxmd.com/read/29903880/real-time-genomic-characterization-of-advanced-pancreatic-cancer-to-enable-precision-medicine
#1
Andrew J Aguirre, Jonathan A Nowak, Nicholas D Camarda, Richard A Moffitt, Arezou A Ghazani, Mehlika Hazar-Rethinam, Srivatsan Raghavan, Jaegil Kim, Lauren K Brais, Dorisanne Ragon, Marisa W Welch, Emma Reilly, Devin McCabe, Lori Marini, Kristin Anderka, Karla Helvie, Nelly Oliver, Ana Babic, Annacarolina Da Silva, Brandon Nadres, Emily E Van Seventer, Heather A Shahzade, Joseph P St Pierre, Kelly P Burke, Thomas E Clancy, James M Cleary, Leona A Doyle, Kunal Jajoo, Nadine J McCleary, Jeffrey A Meyerhardt, Janet E Murphy, Kimmie Ng, Anuj K Patel, Kimberly Perez, Michael H Rosenthal, Douglas A Rubinson, Marvin Ryou, Geoffrey I Shapiro, Ewa Sicinska, Stuart G Silverman, Rebecca J Nagy, Richard B Lanman, Deborah Knoerzer, Dean J Welsch, Matthew B Yurgelun, Charles S Fuchs, Levi A Garraway, Gad Getz, Jason L Hornick, Bruce E Johnson, Matthew H Kulke, Robert J Mayer, Jeffrey W Miller, Paul B Shyn, David A Tuveson, Nikhil Wagle, Jen Jen Yeh, William C Hahn, Ryan B Corcoran, Scott L Carter, Brian M Wolpin
Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole exome sequencing and RNA-sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data...
June 14, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29877921/alk-expression-in-angiomatoid-fibrous-histiocytoma-a-potential-diagnostic-pitfall
#2
Alison L Cheah, Youran Zou, Christopher Lanigan, Steven D Billings, Brian P Rubin, Jason L Hornick, John R Goldblum
We recently encountered a case of primary pulmonary angiomatoid fibrous histiocytoma (AFH), which was initially misdiagnosed as inflammatory myofibroblastic tumor (IMT) based in part on anaplastic lymphoma kinase (ALK) expression by immunohistochemistry (IHC). Prompted by this experience, we evaluated ALK expression in 11 AFH, 15 IMT, and 11 follicular dendritic cell sarcomas using 3 different antibody clones: D5F3, 5A4, and ALK1. ALK IHC positive cases were analyzed with fluorescence in situ hybridization (FISH) using dual color ALK break-apart probe kit...
June 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29863809/evaluation-of-pan-trk-immunohistochemistry-in-infantile-fibrosarcoma-lipofibromatosis-like-neural-tumor-and-histologic-mimics
#3
Yin P Hung, Christopher D M Fletcher, Jason L Hornick
AIMS: Infantile fibrosarcoma is characterized by intersecting fascicles of spindle cells and ETV6-NTRK3 gene fusion in most cases. Given histologic overlap with other spindle-cell tumors, the diagnosis can be challenging and often requires molecular confirmation. A recently developed pan-TRK antibody shows promise for identifying tumors with NTRK fusions. The purpose of this study was to evaluate the potential diagnostic utility of pan-TRK immunohistochemistry for infantile fibrosarcoma...
June 4, 2018: Histopathology
https://www.readbyqxmd.com/read/29863547/expression-of-pax3-distinguishes-biphenotypic-sinonasal-sarcoma-from-histologic-mimics
#4
Vickie Y Jo, Adrián Mariño-Enríquez, Christopher D M Fletcher, Jason L Hornick
Biphenotypic sinonasal sarcoma (BSNS) is a distinctive, anatomically restricted, low-grade spindle cell sarcoma that shows considerable histologic overlap with other cellular spindle cell neoplasms. This tumor type shows both myogenic and neural differentiation, which can be demonstrated by immunohistochemistry; however, the available diagnostic markers are relatively nonspecific. BSNS is characterized by PAX3 rearrangements, with MAML3 as the most common fusion partner. Our aim was to determine whether immunohistochemistry using a monoclonal PAX3 antibody could distinguish BSNS from potential histologic mimics, as well as to evaluate a widely available polyclonal PAX8 antibody, which is known to cross-react with other paired box transcription factor family members...
May 31, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29861296/the-ss18-ssx-fusion-oncoprotein-hijacks-baf-complex-targeting-and-function-to-drive-synovial-sarcoma
#5
Matthew J McBride, John L Pulice, Hannah C Beird, Davis R Ingram, Andrew R D'Avino, Jack F Shern, Gregory W Charville, Jason L Hornick, Robert T Nakayama, Enrique M Garcia-Rivera, Dejka M Araujo, Wei-Lien Wang, Jen-Wei Tsai, Michelle Yeagley, Andrew J Wagner, P Andrew Futreal, Javed Khan, Alexander J Lazar, Cigall Kadoch
Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes...
May 23, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29800950/anthracycline-gemcitabine-and-pazopanib-in-epithelioid-sarcoma-a-multi-institutional-case-series
#6
Anna Maria Frezza, Robin L Jones, Salvatore Lo Vullo, Naofumi Asano, Francesca Lucibello, Eytan Ben-Ami, Ravin Ratan, Pawel Teterycz, Kjetil Boye, Mehdi Brahmi, Emanuela Palmerini, Alexander Fedenko, Bruno Vincenzi, Antonella Brunello, Ingrid M E Desar, Robert S Benjamin, Jean Yves Blay, Javier Martin Broto, Paolo G Casali, Hans Gelderblom, Giovanni Grignani, Alessandro Gronchi, Kirsten Sundby Hall, Olivier Mir, Piotr Rutkowski, Andrew J Wagner, Olga Anurova, Paola Collini, Angelo P Dei Tos, Uta Flucke, Jason L Hornick, Ingvild Lobmaier, Terrier Philippe, Piero Picci, Dominique Ranchere, Salvatore L Renne, Marta Sbaraglia, Khin Thway, Michal Wagrodzki, Wei-Lien Wang, Akihiko Yoshida, Luigi Mariani, Akira Kawai, Silvia Stacchiotti
Importance: Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. Objective: To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. Design, Setting, and Participants: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016...
April 12, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29757500/immunohistochemistry-for-histone-h3g34w-and-h3k36m-is-highly-specific-for-giant-cell-tumor-of-bone-and-chondroblastoma-respectively-in-fna-and-core-needle-biopsy
#7
Inga-Marie Schaefer, Jonathan A Fletcher, G Petur Nielsen, Angela R Shih, Marco L Ferrone, Jason L Hornick, Xiaohua Qian
BACKGROUND: Diagnosing giant cell-rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation-specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell-rich bone tumors on fine-needle aspiration and core needle biopsy specimens...
May 14, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29741745/prospective-feasibility-and-safety-assessment-of-surgical-biopsy-for-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#8
Nalin Gupta, Liliana C Goumnerova, Peter Manley, Susan N Chi, Donna Neuberg, Maneka Puligandla, Jason Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Joshua B Rubin, Karen Gauvain, David Limbrick, Jeffrey Leonard, J Russel Geyer, Sarah Leary, Samuel Browd, Zhihong Wang, Sandeep Sood, Anne Bendel, Mahmoud Nagib, Sharon Gardner, Matthias A Karajannis, David Harter, Kanyalakshmi Ayyanar, William Gump, Daniel C Bowers, Bradley Weprin, Tobey J MacDonald, Dolly Aguilera, Barunashish Brahma, Nathan J Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Sabine Mueller, Anu Banerjee, Amy-Lee Bredlau, Sri Gururangan, Herbert Fuchs, Kenneth J Cohen, George Jallo, Kathleen Dorris, Michael Handler, Melanie Comito, Mark Dias, Kellie Nazemi, Lissa Baird, Jeff Murray, Neal Lindeman, Jason L Hornick, Hayley Malkin, Claire Sinai, Lianne Greenspan, Karen D Wright, Michael Prados, Pratiti Bandopadhayay, Keith L Ligon, Mark W Kieran
Background: Diagnosis of diffuse intrinsic pontine gliomas (DIPG) has relied on imaging studies since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG...
May 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29683816/immunohistochemical-detection-and-molecular-characterization-of-idh-mutant-sinonasal-undifferentiated-carcinomas
#9
Jeffrey K Mito, Justin A Bishop, Peter M Sadow, Edward B Stelow, William C Faquin, Stacey E Mills, Jeffrey F Krane, Christopher A French, Christopher D M Fletcher, Jason L Hornick, Lynette M Sholl, Vickie Y Jo
Recent studies have identified recurrent isocitrate dehydrogenase 2 (IDH2) mutations in a subset of sinonasal undifferentiated carcinomas (SNUCs); however, the true frequency of IDH mutations in SNUC is unknown. We evaluated the utility of mutation-specific IDH1/2 immunohistochemistry (IHC) in a large multi-institutional cohort of SNUC and morphologic mimics. IHC using a multispecific antibody for IDH1/2 (R132/R172) mutant protein was performed on 193 sinonasal tumors including: 53 SNUCs, 8 poorly differentiated carcinomas (PDCARs) and 132 histologic mimics...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29608884/detection-of-mutations-in-barrett-s-esophagus-before-progression-to-high-grade-dysplasia-or-adenocarcinoma
#10
Matthew D Stachler, Nicholas D Camarda, Christopher Deitrick, Anthony Kim, Agoston T Agoston, Robert D Odze, Jason L Hornick, Anwesha Nag, Aaron R Thorner, Matthew Ducar, Amy Noffsinger, Richard H Lash, Mark Redston, Scott L Carter, Jon M Davison, Adam J Bass
BACKGROUND & AIMS: Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress. METHODS: We performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10)...
March 31, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29605270/pumpless-arteriovenous-extracorporeal-membrane-oxygenation-a-novel-mode-of-respiratory-support-in-a-lamb-model-of-congenital-diaphragmatic-hernia
#11
Emily A Partridge, Marcus G Davey, Matthew Hornick, Kevin C Dysart, Aliza Olive, Robert Caskey, James T Connelly, Holly L Hedrick, William H Peranteau, Alan W Flake
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is commonly required in neonates with congenital diaphragmatic hernia (CDH) complicated by pulmonary hypertension (PH). ECMO carries significant risk, and is contraindicated in the setting of extreme prematurity or intracranial hemorrhage. Pumpless arteriovenous ECMO (P-ECMO) may represent an alternative for respiratory support. The present study summarizes our initial experience with P-ECMO in a lamb model of CDH. STUDY DESIGN: Surgical creation of CDH was performed at 65-75days' gestation...
March 9, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29420353/clusterin-in-neuroendocrine-epithelial-neoplasms-absence-of-expression-in-a-well-differentiated-tumor-suggests-a-jejunoileal-origin
#12
Thomas W Czeczok, Kristen M Stashek, Jessica E Maxwell, Thomas M O'Dorisio, James R Howe, Jason L Hornick, Andrew M Bellizzi
Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs...
February 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29392729/umbilical-cannulation-optimizes-circuit-flows-in-premature-lambs-supported-by-the-extra-uterine-environment-for-neonatal-development-extend
#13
Matthew A Hornick, Marcus G Davey, Emily A Partridge, Ali Y Mejaddam, Patrick E McGovern, Aliza M Olive, Grace Hwang, Jenny Kim, Orlando Castillo, Kathleen Young, Jiancheng Han, Sheng Zhao, James T Connelly, Kevin C Dysart, Jack Rychik, William H Peranteau, Alan W Flake
KEY POINTS: Bronchopulmonary dysplasia is a disease of extreme prematurity that occurs when the immature lung is exposed to gas ventilation. We designed a novel 'artificial womb' system for supporting extreme premature lambs (called EXTEND) that obviates gas ventilation by providing oxygen via a pumpless arteriovenous circuit with the lamb submerged in sterile artificial amniotic fluid. In the present study, we compare different arteriovenous cannulation strategies on EXTEND, including carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery/umbilical vein (UA/UV)...
May 1, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29385322/sox10-keratin-dual-color-immunohistochemistry-an-effective-first-line-test-for-the-workup-of-epithelioid-malignant-neoplasms-in-fna-and-small-biopsy-specimens
#14
Jeffrey K Mito, James R Conner, Jason L Hornick, Edmund S Cibas, Xiaohua Qian
BACKGROUND: The characterization of poorly differentiated neoplasms in fine-needle aspiration (FNA) and small biopsy specimens usually requires immunohistochemistry (IHC) with a panel of markers. Because of an increasing need to preserve limited diagnostic material for tumor genotyping and a mounting demand for cost containment, the authors investigated the usefulness of dual-color IHC with antibodies directed against broad-spectrum keratins and SOX10, a neuroectodermal transcription factor consistently expressed in melanoma, in the workup of epithelioid malignant neoplasms...
March 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29340997/immunohistochemical-biomarkers-of-mesenchymal-neoplasms-in-endocrine-organs-diagnostic-pitfalls-and-recent-discoveries
#15
Yin P Hung, Jason L Hornick
Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma...
January 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#16
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
April 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29332233/pilot-study-of-serial-flt-and-fdg-pet-ct-imaging-to-monitor-response-to-neoadjuvant-chemoradiotherapy-of-esophageal-adenocarcinoma-correlation-with-histopathologic-response
#17
Victor H Gerbaudo, Joseph H Killoran, Chun K Kim, Jason L Hornick, Jonathan A Nowak, Peter C Enzinger, Harvey J Mamon
OBJECTIVE: The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al...
April 2018: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29327718/epithelioid-fibrous-histiocytoma-molecular-characterization-of-alk-fusion-partners-in-23-cases
#18
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327713/expression-of-enhancer-of-zeste-homolog-2-ezh2-protein-in-histiocytic-and-dendritic-cell-neoplasms-with-evidence-for-p-erk1-2-related-but-not-myc-or-p-stat3-related-cell-signaling
#19
Xuejun Tian, Jie Xu, Christopher Fletcher, Jason L Hornick, David M Dorfman
EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. We found that the majority of cases of histiocytic and dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast to benign histiocytic lesions and normal cellular counterparts, which did not show EZH2 expression, suggesting that this molecule may function as an oncogenic protein in these neoplasms...
April 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29282312/nlrp12-mediates-adverse-neutrophil-recruitment-during-influenza-virus-infection
#20
Emma E Hornick, Balaji Banoth, Ann M Miller, Zeb R Zacharias, Nidhi Jain, Mary E Wilson, Katherine N Gibson-Corley, Kevin L Legge, Gail A Bishop, Fayyaz S Sutterwala, Suzanne L Cassel
Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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