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https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#1
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28081303/the-novel-fusion-transcript-nr5a2-klhl29ft-is-generated-by-an-insertion-at-the-klhl29-locus
#2
Zhenguo Sun, Xiquan Ke, Steven L Salzberg, Daehwan Kim, Valentin Antonescu, Yulan Cheng, Binbin Huang, Jee Hoon Song, John M Abraham, Sariat Ibrahim, Hui Tian, Stephen J Meltzer
BACKGROUND: Novel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. METHODS: RNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement...
January 12, 2017: Cancer
https://www.readbyqxmd.com/read/28035047/the-acyltransferase-lycat-controls-specific-phosphoinositides-and-related-membrane-traffic
#3
Leslie N Bone, Roya M Dayam, Minhyoung Lee, Nozomu Kono, Gregory D Fairn, Hiroyuki Arai, Roberto J Botelho, Costin N Antonescu
Phosphoinositides (PIPs) are key regulators of membrane traffic and signaling. The interconversion of PIPs by lipid kinases and phosphatases regulates their functionality. Phosphatidylinositol (PI) and PIPs have a unique enrichment of 1-stearoyl-2-arachidonyl acyl species; however, the regulation and function of this specific acyl profile remains poorly understood. We examined the role of the PI acyltransferase LYCAT in control of PIPs and PIP-dependent membrane traffic. LYCAT silencing selectively perturbed the levels and localization of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol-3-phosphate and the membrane traffic dependent on these specific PIPs but was without effect on phosphatidylinositol-4-phosphate or biosynthetic membrane traffic...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28028572/romanian-medicine-european-medicine
#4
EDITORIAL
Ioan Cristian Stoica, Dinu Antonescu, Adrian Pana, Stefan Mogos, Romain Seil
The aim of the present paper is to present the message transmitted by the Presidential Lecture given during the first congress of arthroscopy organised in Romania, in March 2016, by the Romanian Society of Arthroscopy and Sports Trauma (SRATS). The goal was to present the evolution of medical care in Romania over the years, with the remarkable progress made in the first half of the twentieth century and the current status of arthroscopic surgery as seen from the point of view of medical professionals, as well as from a governmental point of view...
December 28, 2016: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/28009602/ewsr1-fusions-with-creb-family-transcription-factors-define-a-novel-myxoid-mesenchymal-tumor-with-predilection-for-intracranial-location
#5
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Chun-Liang Chen, Sumathi Vaiyapuri, Marc K Rosenblum, Cristina R Antonescu
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities...
December 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#6
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph P Erinjeri, Mark Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina R Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
PURPOSE: A phase Ib study of dasatinib plus ipilimumab in GIST and other sarcomas was performed based on pre-clinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. EXPERIMENTAL DESIGN: A standard 3+3 design was used evaluate the safety, efficacy and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks followed by maintenance every 12 weeks with escalating doses of dasatinib (70mg daily, 100 mg daily or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27914109/bcor-upregulation-in-a-poorly-differentiated-synovial-sarcoma-with-ss18l1-ssx1-fusion-a-pathologic-and-molecular-pitfall
#7
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Samuel Kenan, Samuel Singer, William D Tap, David Swanson, Brendan C Dickson, Cristina R Antonescu
The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here, we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH, which were misinterpreted as a URCS with BCOR gene rearrangements...
December 3, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27859477/primary-cutaneous-adenoid-cystic-carcinoma-with-myb-aberrations-report-of-three-cases-and-comprehensive-review-of-the-literature
#8
Carlos N Prieto-Granada, Lei Zhang, Cristina R Antonescu, Jean M Henneberry, Jane L Messina
Adenoid cystic carcinoma (ACC) is a relatively rare slow-growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22-23;p23-24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report three additional cases of PCACC harboring MYB aberrations. The tumors presented in three males aged 43, 81 and 55 years old and affected the extremities in the first two patients and the scalp in the third one...
February 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27757134/circulating-plasma-micro-rnas-in-patients-with-major-depressive-disorder-treated-with-antidepressants-a-pilot-study
#9
Virgil Radu Enatescu, Ion Papava, Ileana Enatescu, Mirela Antonescu, Andrei Anghel, Edward Seclaman, Ioan Ovidiu Sirbu, Catalin Marian
OBJECTIVE: Significant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants. METHODS: At the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done...
September 2016: Psychiatry Investigation
https://www.readbyqxmd.com/read/27689858/long-term-effect-of-chemotherapy-intensity-modulated-radiation-therapy-chemo-imrt-on-dentofacial-development-in-head-and-neck-rhabdomyosarcoma-patients
#10
Adepitan A Owosho, Paul Brady, Suzanne L Wolden, Leonard H Wexler, Cristina R Antonescu, Joseph M Huryn, Cherry L Estilo
Dentofacial developmental abnormalities have been reported in head and neck rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy technique and chemotherapy. This current study investigates dentofacial long-term effects among HNRMS survivors managed with intensity-modulated radiotherapy (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal radiotherapy technique, which delivers high doses of radiation to the tumor target while minimizing doses received by the surrounding normal tissues...
September 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27688110/a-clinicopathologic-study-of-head-and-neck-rhabdomyosarcomas-showing-foxo1-fusion-positive-alveolar-and-myod1-mutant-sclerosing-are-associated-with-unfavorable-outcome
#11
Adepitan A Owosho, Shih-Chiang Huang, Sonja Chen, Shruti Kashikar, Cherry L Estilo, Suzanne L Wolden, Leonard H Wexler, Joseph M Huryn, Cristina R Antonescu
BACKGROUND: Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort...
October 2016: Oral Oncology
https://www.readbyqxmd.com/read/27631520/novel-high-grade-endometrial-stromal-sarcoma-a-morphologic-mimicker-of-myxoid-leiomyosarcoma
#12
Lien N Hoang, Amandeep Aneja, Niamh Conlon, Deborah F Delair, Sumit Middha, Ryma Benayed, Martee L Hensley, Kay J Park, Travis J Hollmann, Meera R Hameed, Cristina R Antonescu, Robert A Soslow, Sarah Chiang
Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity...
January 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27566443/a-phase-ii-study-of-axitinib-ag-013736-in-patients-with-incurable-adenoid-cystic-carcinoma
#13
A L Ho, L Dunn, E J Sherman, M G Fury, S S Baxi, R Chandramohan, S Dogan, L G T Morris, G D Cullen, S Haque, C S Sima, A Ni, C R Antonescu, N Katabi, D G Pfister
BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27565001/tfeb-amplified-renal-cell-carcinomas-an-aggressive-molecular-subset-demonstrating-variable-melanocytic-marker-expression-and-morphologic-heterogeneity
#14
Pedram Argani, Victor E Reuter, Lei Zhang, Yun-Shao Sung, Yi Ning, Jonathan I Epstein, George J Netto, Cristina R Antonescu
Renal cell carcinomas (RCCs) with the t(6;11)(p21;q12) chromosome translocation are low-grade RCC which often occur in young patients. They typically feature an unusual biphasic morphology characterized by nests of larger epithelioid cells surrounding intraluminal collections of smaller cells clustered around basement membrane material. The t(6;11)(p21;q12) translocation fuses the Alpha (MALAT1) gene with the TFEB transcription factor gene, resulting in upregulated expression of intact native TFEB that drives the aberrant expression of melanocytic markers which is a hallmark of this distinctive neoplasm...
November 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27537276/expanding-the-molecular-signature-of-ossifying-fibromyxoid-tumors-with-two-novel-gene-fusions-crebbp-bcorl1-and-kdm2a-wwtr1
#15
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Chun-Liang Chen, Shih-Chiang Huang, Cristina R Antonescu
Ossifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent gene fusions involving either PHF1 or BCOR have been found in 85% of OFMT, including typical and malignant examples. As a subset of OFMT still lack known genetic abnormalities, we identified two OFMTs negative for PHF1 and BCOR rearrangements, which were subjected to transcriptome analysis for fusion discovery. The RNA sequencing found a novel CREBBP-BCORL1 fusion candidate in an axillary mass of a 51 year-old male and a KDM2A-WWTR1 in a thigh mass of a 36 year-old male...
January 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27508001/relationship-of-suicide-rates-with-climate-and-economic-variables-in-europe-during-2000-2012
#16
Konstantinos N Fountoulakis, Isaia Chatzikosta, Konstantinos Pastiadis, Prodromos Zanis, Wolfram Kawohl, Ad J F M Kerkhof, Alvydas Navickas, Cyril Höschl, Dusica Lecic-Tosevski, Eliot Sorel, Elmars Rancans, Eva Palova, Georg Juckel, Goran Isacsson, Helena Korosec Jagodic, Ileana Botezat-Antonescu, Janusz Rybakowski, Jean Michel Azorin, John Cookson, John Waddington, Peter Pregelj, Koen Demyttenaere, Luchezar G Hranov, Lidija Injac Stevovic, Lucas Pezawas, Marc Adida, Maria Luisa Figuera, Miro Jakovljević, Monica Vichi, Giulio Perugi, Ole A Andreassen, Olivera Vukovic, Paraskevi Mavrogiorgou, Peeter Varnik, Peter Dome, Petr Winkler, Raimo K R Salokangas, Tiina From, Vita Danileviciute, Xenia Gonda, Zoltan Rihmer, Jonas Forsman, Anne Grady, Thomas Hyphantis, Ingrid Dieset, Susan Soendergaard, Maurizio Pompili, Per Bech
BACKGROUND: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. METHODS: Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered...
2016: Annals of General Psychiatry
https://www.readbyqxmd.com/read/27489582/similar-requirement-for-clathrin-in-egf-and-hgf-stimulated-akt-phosphorylation
#17
Stefanie Lucarelli, Rohan Pandey, Gurjeet Judge, Costin N Antonescu
Receptor tyrosine kinases, such as the epidermal growth factor (EGF) receptor (EGFR) and Met lead to activation of intracellular signals including Akt, a critical regulator of cell survival, metabolism and proliferation. Upon binding their respective ligands, each of these receptors is recruited into clathrin coated pits (CCPs) eventually leading to endocytosis. We have recently shown that phosphorylation of Gab1 and Akt following EGFR activation requires clathrin, but does not require receptor endocytosis...
May 2016: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/27470968/pd-1-pd-l1-blockade-enhances-t-cell-activity-and-antitumor-efficacy-of-imatinib-in-gastrointestinal-stromal-tumors
#18
Adrian M Seifert, Shan Zeng, Jennifer Q Zhang, Teresa S Kim, Noah A Cohen, Michael J Beckman, Benjamin D Medina, Joanna H Maltbaek, Jennifer K Loo, Megan H Crawley, Ferdinand Rossi, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
PURPOSE: Tyrosine kinase inhibitors are effective in gastrointestinal stromal tumors (GISTs) but often are of transient benefit as resistance commonly develops. Immunotherapy, particularly blockade of the inhibitory receptor programmed death 1 (PD-1) or the ligand programmed death ligand 1 (PD-L1), has shown effectiveness in a variety of cancers. The functional effects of PD-1/PD-L1 blockade are unknown in GISTs. EXPERIMENTAL DESIGN: We analyzed tumor and matched blood samples from 85 patients with GISTs and determined the expression of immune checkpoint molecules using flow cytometry...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27428733/bcor-overexpression-is-a-highly-sensitive-marker-in-round-cell-sarcomas-with-bcor-genetic-abnormalities
#19
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Achim A Jungbluth, Shih-Chiang Huang, Pedram Argani, Narasimhan P Agaram, Angelica Zin, Rita Alaggio, Cristina R Antonescu
With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum of EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature including high BCOR mRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high BCOR gene expression...
December 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27385213/anaplastic-lymphoma-kinase-aberrations-correlate-with-metastatic-features-in-pediatric-rhabdomyosarcoma
#20
Patrizia Gasparini, Michela Casanova, Raffaella Villa, Paola Collini, Rita Alaggio, Angelica Zin, Paolo Bonvini, Cristina R Antonescu, Renata Boldrini, Roberto Caserini, Massimo Moro, Giovanni Centonze, Cristina Meazza, Maura Massimino, Luca Bergamaschi, Roberto Luksch, Stefano Chiaravalli, Gianni Bisogno, Nadia Zaffaroni, Maria Grazia Daidone, Gabriella Sozzi, Andrea Ferrari
Rhabdomyosarcoma (RMS) is the most frequent soft tissue tumor in childhood and arises from immature mesenchymal cells committed to skeletal muscle differentiation. Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in several cancers. Moreover, ALK full-length receptor protein has been observed in RMS, although its clinical and functional significance is yet controversial. The role of ALK and its clinical relevance were investigated in a selected cohort of 74 FFPE pediatric RMS and a panel of RMS cell lines, evaluating its gene and protein status, utilizing Fluorescent In Situ Hybridization (FISH), immunohistochemistry (IHC) and Western blot approaches...
13, 2016: Oncotarget
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