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https://www.readbyqxmd.com/read/29774203/small-rho-gtpases-and-the-effector-vipa-mediate-the-invasion-of-epithelial-cells-by-filamentous-legionella-pneumophila
#1
Akriti Prashar, María Eugenia Ortiz, Stefanie Lucarelli, Elizabeth Barker, Zohreh Tabatabeiyazdi, Feras Shamoun, Deepa Raju, Costin Antonescu, Cyril Guyard, Mauricio R Terebiznik
Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates β1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29587244/epigenetic-regulation-of-vascular-nadph-oxidase-expression-and-reactive-oxygen-species-production-by-histone-deacetylase-dependent-mechanisms-in-experimental-diabetes
#2
Simona-Adriana Manea, Mihaela-Loredana Antonescu, Ioana Madalina Fenyo, Monica Raicu, Maya Simionescu, Adrian Manea
Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox) contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC)-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29572501/array-based-dna-methylation-profiling-in-sarcomas-with-small-blue-round-cell-histology-provides-valuable-diagnostic-information
#3
Christian Koelsche, Wolfgang Hartmann, Daniel Schrimpf, Damian Stichel, Susanne Jabar, Andreas Ranft, David E Reuss, Felix Sahm, David T W Jones, Melanie Bewerunge-Hudler, Marcel Trautmann, Thomas Klingebiel, Christian Vokuhl, Manfred Gessler, Eva Wardelmann, Iver Petersen, Daniel Baumhoer, Uta Flucke, Cristina Antonescu, Manel Esteller, Stefan Fröhling, Marcel Kool, Stefan M Pfister, Gunhild Mechtersheimer, Uta Dirksen, Andreas von Deimling
Undifferentiated solid tumors with small blue round cell histology and expression of CD99 mostly resemble Ewing sarcoma. However, they also may include other tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell osteosarcoma. Definitive classification usually requires detection of entity-specific mutations. While this approach identifies the majority of Ewing sarcomas, a subset of lesions remains unclassified and, therefore, has been termed "Ewing-like sarcomas" or small blue round cell tumors not otherwise specified...
March 23, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29553955/ntrk-fusions-define-a-novel-uterine-sarcoma-subtype-with-features-of-fibrosarcoma
#4
Sarah Chiang, Paolo Cotzia, David M Hyman, Alexander Drilon, William D Tap, Lei Zhang, Jaclyn F Hechtman, Denise Frosina, Achim A Jungbluth, Rajmohan Murali, Kay J Park, Robert A Soslow, Esther Oliva, A John Iafrate, Ryma Benayed, Marc Ladanyi, Cristina R Antonescu
Tropomyosin receptor kinase (Trk) inhibitors have shown high response rates in patients with tumors harboring NTRK fusions. We identified 4 NTRK fusion-positive uterine sarcomas that should be distinguished from leiomyosarcoma and undifferentiated uterine sarcoma. NTRK rearrangements were detected by fluorescence in situ hybridization (FISH) and/or targeted RNA or DNA sequencing in 4 undifferentiated uterine sarcomas with spindle cell morphology. Because of histologic overlap with leiomyosarcoma, TrkA and pan-Trk immunohistochemistry was performed in 97 uterine leiomyosarcomas...
March 16, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29533464/genetic-analyses-of-undifferentiated-small-round-cell-sarcoma-identifies-a-novel-sarcoma-subtype-with-a-recurrent-crtc1-ss18-gene-fusion
#5
Abdullah Alholle, Marie Karanian, Anna T Brini, Mark R Morris, Vinodh Kannappan, Stefania Niada, Angela Niblett, Dominique Ranchère-Vince, Daniel Pissaloux, Christophe Delfour, Aurelie Maran-Gonzalez, Cristina R Antonescu, Vaiyapuri Sumathi, Franck Tirode, Farida Latif
In recent years, undifferentiated small round cell sarcomas (USRCSs) have been divided into a variety of new, rare, sarcoma subtypes, including the group of Ewing-like sarcomas, which have the morphological appearance of Ewing sarcomas, but carry CIC-DUX4, BCOR-CCNB3 and other gene fusions different from the classic EWSR1-ETS gene fusion. Using high-throughput RNA-sequencing (RNA-seq) analyses, we identified a novel recurrent gene fusion, CRTC1-SS18, in two cases of USRCS that lacked any known translocation...
June 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29467128/macrophages-and-cd8-t-cells-mediate-the-antitumor-efficacy-of-combined-cd40-ligation-and-imatinib-therapy-in-gastrointestinal-stromal-tumors
#6
Jennifer Q Zhang, Shan Zeng, Gerardo A Vitiello, Adrian M Seifert, Benjamin D Medina, Michael J Beckman, Jennifer K Loo, Juan Santamaria-Barria, Joanna H Maltbaek, Nesteene J Param, John A Moral, Julia N Zhao, Vinod Balachandran, Ferdinand Rossi, Cristina R Antonescu, Ronald P DeMatteo
Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective but typically culminates in resistance and is rarely curative. Immunotherapy has potential application to GIST, as we previously showed that T-cell checkpoint blockade increases the antitumor effects of imatinib. Here, we showed that ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor-associated macrophages (TAMs) in vivo in a knock-in mouse model of GIST harboring a germline mutation in Kit exon 11. Activated TAMs had greater TNFα production and NFκB signaling and directly inhibited tumor cells in vitro Anti-CD40 required concomitant therapy with imatinib for efficacy and depended on TAMs, and to a lesser extent CD8+ T cells, but not on CD4+ T cells or B cells...
April 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29443014/recurrent-ret-gene-rearrangements-in-intraductal-carcinomas-of-salivary-gland
#7
Ilan Weinreb, Justin A Bishop, Simion I Chiosea, Raja R Seethala, Bayardo Perez-Ordonez, Lei Zhang, Yun-Shao Sung, Chun-Liang Chen, Adel Assaad, Bahram R Oliai, Cristina R Antonescu
Intraductal carcinoma (IC) is the World Health Organization designation for lesions previously called low-grade cribriform cystadenocarcinoma. The relationship of IC to salivary duct carcinoma (SDC) is controversial, but currently these are considered distinct entities. It is hypothesized that IC and SDC should have different genomic signatures that may be identifiable by next-generation sequencing. A total of 23 ICs were identified: 14 pure IC and 9 invasive carcinomas with an intraductal component. Five invasive carcinomas were subjected to next-generation paired-end RNA sequencing...
April 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29370992/nivolumab-with-or-without-ipilimumab-treatment-for-metastatic-sarcoma-alliance-a091401-two-open-label-non-comparative-randomised-phase-2-trials
#8
Sandra P D'Angelo, Michelle R Mahoney, Brian A Van Tine, James Atkins, Mohammed M Milhem, Balkrishna N Jahagirdar, Cristina R Antonescu, Elise Horvath, William D Tap, Gary K Schwartz, Howard Streicher
BACKGROUND: Patients with metastatic sarcoma have limited treatment options. Nivolumab and ipilimumab are monoclonal antibodies targeting PD-1 and CTLA-4, respectively. We investigated the activity and safety of nivolumab alone or in combination with ipilimumab in patients with locally advanced, unresectable, or metastatic sarcoma. METHODS: We did a multicentre, open-label, non-comparative, randomised, phase 2 study that enrolled patients aged 18 years or older and had central pathology confirmation of sarcoma with at least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) 1...
March 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29366253/nadph-oxidase-5-expression-is-regulated-by-histone-acetyltransferase-1-and-p300-dependent-in-human-macrophages
#9
Mihaela-Loredana Antonescu, Simona-Adriana Manea, Maya Simionescu, Adrian Manea
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29360641/cop1-det1-ets-axis-regulates-erk-transcriptome-and-sensitivity-to-mapk-inhibitors
#10
Yuanyuan Xie, Zhen Cao, Elissa Wp Wong, Youxin Guan, Wenfu Ma, Jenny Q Zhang, Edward G Walczak, Devan Murphy, Leili Ran, Inna Sirota, Shangqian Wang, Shipra Shukla, Dong Gao, Simon Rv Knott, Kenneth Chang, Justin Leu, John Wongvipat, Cristina R Antonescu, Gregory Hannon, Ping Chi, Yu Chen
Aberrant activation of MAPK signaling leads to the activation of oncogenic transcriptomes. How MAPK signaling is coupled with the transcriptional response in cancer is not fully understood. In 2 MAPK-activated tumor types, gastrointestinal stromal tumor and melanoma, we found that ETV1 and other Pea3-ETS transcription factors are critical nuclear effectors of MAPK signaling that are regulated through protein stability. Expression of stabilized Pea3-ETS factors can partially rescue the MAPK transcriptome and cell viability after MAPK inhibition...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29356724/nutm1-gene-fusions-characterize-a-subset-of-undifferentiated-soft-tissue-and-visceral-tumors
#11
Brendan C Dickson, Yun-Shao Sung, Marc K Rosenblum, Victor E Reuter, Mohammed Harb, Jay S Wunder, David Swanson, Cristina R Antonescu
NUT midline carcinoma is an aggressive tumor that occurs mainly in the head and neck and, less frequently, the mediastinum and lung. Following identification of an index case of a NUTM1 fusion positive undifferentiated soft tissue tumor, we interrogated additional cases of primary undifferentiated soft tissue and visceral tumors for NUTM1 abnormalities. Targeted next-generation sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue, and results validated by fluorescence in situ hybridization using custom bacterial artificial chromosome probes...
May 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29300189/bcor-ccnb3-fusion-positive-sarcomas-a-clinicopathologic-and-molecular-analysis-of-36-cases-with-comparison-to-morphologic-spectrum-and-clinical-behavior-of-other-round-cell-sarcomas
#12
Yu-Chien Kao, Adepitan A Owosho, Yun-Shao Sung, Lei Zhang, Yumi Fujisawa, Jen-Chieh Lee, Leonard Wexler, Pedram Argani, David Swanson, Brendan C Dickson, Christopher D M Fletcher, Cristina R Antonescu
BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis...
October 25, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29246941/mitochondrial-inhibition-augments-the-efficacy-of-imatinib-by-resetting-the-metabolic-phenotype-of-gastrointestinal-stromal-tumor
#13
Gerardo A Vitiello, Benjamin D Medina, Shan Zeng, Timothy G Bowler, Jennifer Q Zhang, Jennifer K Loo, Nesteene J Param, Mengyuan Liu, Alec J Moral, Julia N Zhao, Ferdinand Rossi, Cristina R Antonescu, Vinod P Balachandran, Justin R Cross, Ronald P DeMatteo
Purpose: Imatinib dramatically reduces gastrointestinal stromal tumor (GIST)18 F-FDG uptake, providing an early indicator of treatment response. Despite decreased glucose internalization, many GIST cells persist, suggesting that alternative metabolic pathways are used for survival. The role of mitochondria in imatinib-treated GIST is largely unknown. Experimental Design: We quantified the metabolic activity of several human GIST cell lines. We treated human GIST xenografts and genetically engineered KitV558del/+ mice with the mitochondrial oxidative phosphorylation inhibitor VLX600 in combination with imatinib and analyzed tumor volume, weight, histology, molecular signaling, and cell cycle activity...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29192652/zc3h7b-bcor-high-grade-endometrial-stromal-sarcomas-a-report-of-17-cases-of-a-newly-defined-entity
#14
Natasha Lewis, Robert A Soslow, Deborah F Delair, Kay J Park, Rajmohan Murali, Travis J Hollmann, Ben Davidson, Francesca Micci, Ioannis Panagopoulos, Lien N Hoang, Javier A Arias-Stella, Esther Oliva, Robert H Young, Martee L Hensley, Mario M Leitao, Meera Hameed, Ryma Benayed, Marc Ladanyi, Denise Frosina, Achim A Jungbluth, Cristina R Antonescu, Sarah Chiang
High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three initial endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, we herein investigate the clinicopathologic features of this genetic subset by expanding the analysis to 17 such tumors. All of them occurred in adult women with a median age of 54 (range, 28-71) years. They were predominantly based in the endomyometrium and demonstrated tongue-like and/or pushing myometrial invasion...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29162563/foxf1-defines-the-core-regulatory-circuitry-in-gastrointestinal-stromal-tumor
#15
Leili Ran, Yuedan Chen, Jessica Sher, Elissa W P Wong, Devan Murphy, Jenny Q Zhang, Dan Li, Kemal Deniz, Inna Sirota, Zhen Cao, Shangqian Wang, Youxin Guan, Shipra Shukla, Katie Yang Li, Alan Chramiec, Yuanyuan Xie, Deyou Zheng, Richard P Koche, Cristina R Antonescu, Yu Chen, Ping Chi
The cellular context that integrates upstream signaling and downstream nuclear response dictates the oncogenic behavior and shapes treatment responses in distinct cancer types. Here, we uncover that in gastrointestinal stromal tumor (GIST), the forkhead family member FOXF1 directly controls the transcription of two master regulators, KIT and ETV1 , both required for GIST precursor-interstitial cells of Cajal lineage specification and GIST tumorigenesis. Further, FOXF1 colocalizes with ETV1 at enhancers and functions as a pioneer factor that regulates the ETV1-dependent GIST lineage-specific transcriptome through modulation of the local chromatin context, including chromatin accessibility, enhancer maintenance, and ETV1 binding...
February 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29119645/high-sensitivity-of-fish-analysis-in-detecting-homozygous-smarcb1-deletions-in-poorly-differentiated-chordoma-a-clinicopathologic-and-molecular-study-of-nine-cases
#16
Adepitan A Owosho, Lei Zhang, Marc K Rosenblum, Cristina R Antonescu
Poorly differentiated chordomas (PDCs) represent a rare subset of notochordal neoplasms, affecting primarily children and associated with an aggressive outcome. In contrast to conventional chordomas, PDC show solid growth and increased cellularity, cytologic atypia, and mitotic activity. Recent studies have shown that PDCs are characterized by recurrent deletions encompassing the SMARCB1 locus, resulting in consistent loss of nuclear SMARCB1 expression. Thus PDC joined the expanding family of SMARCB1-deficient tumors characterized by various SMARCB1 structural abnormalities, ranging from large homozygous deletions to small intragenic mutations...
February 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29058144/rectal-gastrointestinal-stromal-tumor-gist-in-the-era-of-imatinib-organ-preservation-and-improved-oncologic-outcome
#17
Michael J Cavnar, Lin Wang, Vinod P Balachandran, Cristina R Antonescu, William D Tap, Mary Keohan, Sam Singer, Larissa Temple, Garrett M Nash, Martin R Weiser, Jose G Guillem, Julio Garcia Aguilar, Ronald P DeMatteo, Philip B Paty
BACKGROUND: Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib. METHODS: Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan-Meier method...
December 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29039030/size-and-location-are-the-most-important-risk-factors-for-malignant-behavior-in-resected-solitary-fibrous-tumors
#18
Sepideh Gholami, Michael R Cassidy, Amanda Kirane, Deborah Kuk, Bhumika Zanchelli, Christina R Antonescu, Samuel Singer, Murray Brennan
PURPOSE: While previously thought to be clinically indolent, recent data suggest significant late metastatic capacity of solitary fibrous tumors (SFTs). We define prognostic factors for recurrence and disease-specific death (DSD) in resected primary SFTs. METHODS: Resected primary SFTs from 1982 to 2015 were identified from a prospective, single institutional database. Risk factors for local (LR) and distant recurrence (DR), and DSD were assessed using competing risk analysis...
December 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28951624/erratum-pgbd5-promotes-site-specific-oncogenic-mutations-in-human-tumors
#19
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
No abstract text is available yet for this article.
September 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28939748/in-depth-genetic-analysis-of-sclerosing-epithelioid-fibrosarcoma-reveals-recurrent-genomic-alterations-and-potential-treatment-targets
#20
Elsa Arbajian, Florian Puls, Cristina R Antonescu, Fernanda Amary, Raf Sciot, Maria Debiec-Rychter, Vaiyapuri P Sumathi, Marcus Järås, Linda Magnusson, Jenny Nilsson, Jakob Hofvander, Fredrik Mertens
Purpose: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphologic characteristics of both SEF and LGFMS, hence they are known as hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The current study aimed to further characterize SEF and hybrid SEF/LGFMS genetically to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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