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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
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 30, 2016: Pediatric Hematology and Oncology
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
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...
September 14, 2016: American Journal of Surgical Pathology
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
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
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...
August 18, 2016: Genes, Chromosomes & Cancer
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
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
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 tumor (GIST), 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 GIST. EXPERIMENTAL DESIGN: We analyzed tumor and matched blood samples from 85 patients with GIST and determined the expression of immune checkpoint molecules using flow cytometry...
July 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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...
July 13, 2016: American Journal of Surgical Pathology
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, MariaGrazia 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...
July 1, 2016: Oncotarget
Farnaz Fekri, Ralph Christian Delos Santos, Raffi Karshafian, Costin N Antonescu
Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment...
2016: PloS One
Narasimhan P Agaram, Lei Zhang, Yun-Shao Sung, Chun-Liang Chen, Catherine T Chung, Cristina R Antonescu, Christopher Dm Fletcher
The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation...
October 2016: American Journal of Surgical Pathology
Mircea Filip, Miruna Nicolae, Andrei Filip, Cristina Antonescu, Carmen Dragne, Grigorios Triantafyllidis, Raluca Moisescu, Irina Lutic, Ileana Ungureanu, Anamaria Teodorov
The purpose of the study was to evaluate the refractive results on a large cohort of patients who were implanted spherical or toric multifocal IOL's for cataract surgery or for refractive purpose. Preoperative refractive investigations included auto refractometer topography, pentacam, contact and noncontact biometry and many non-refractive investigations. The target in multifocal IOL usage was emmetropia and it was achieved in most cases. Ametropia occurrence involved correction in different ways.
January 2016: Romanian Journal of Ophthalmology
Shih-Chiang Huang, Lei Zhang, Yun-Shao Sung, Chun-Liang Chen, Yu-Chien Kao, Narasimhan P Agaram, Cristina R Antonescu
SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma...
October 2016: Genes, Chromosomes & Cancer
Majid Maybody, Ravinder K Grewal, John H Healey, Cristina R Antonescu, Louise Fanchon, Sinchun Hwang, Jorge A Carrasquillo, Assen Kirov, Azeez Farooki
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by small benign tumors of mesenchymal origin also known as phosphaturic mesenchymal tumors mixed connective tissue variant. Excellent prognosis is expected with eradication of the culprit tumor. These small tumors are notoriously difficult to localize with conventional imaging studies; this often leads to an extensive work up and prolonged morbidity. We report a patient with clinical diagnosis of TIO whose culprit tumor was localized with Ga-68 DOTATOC PET/CT and MRI...
September 2016: Cardiovascular and Interventional Radiology
Lisa M Rooper, Shih-Chiang Huang, Cristina R Antonescu, William H Westra, Justin A Bishop
Biphenotypic sinonasal sarcoma (BSNS) is a recently recognized low-grade sarcoma that exhibits both neural and myogenic differentiation. This unique dual phenotype stems from recurrent rearrangements in PAX3, a transcription factor that promotes commitment along both lineages. While identification of PAX3 rearrangements by fluorescence in situ hybridization (FISH) can confirm a BSNS diagnosis, this assay is not widely available. This study evaluates whether an expanded immunohistochemical panel can facilitate recognition of BSNS without molecular analysis...
September 2016: Human Pathology
Mark A Dickson, Gary K Schwartz, Mary Louise Keohan, Sandra P D'Angelo, Mrinal M Gounder, Ping Chi, Cristina R Antonescu, Jonathan Landa, Li-Xuan Qin, Aimee M Crago, Samuel Singer, Andrew Koff, William D Tap
IMPORTANCE: More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. The selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and xenografts. Our prior phase 2 study demonstrated that treatment with palbociclib (200 mg daily for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. It is important to understand whether palbociclib at a new dose and schedule-125 mg daily for 21 days every 28 days-results in clinical benefit and manageable toxic effects...
July 1, 2016: JAMA Oncology
Lien Spans, Christopher Dm Fletcher, Cristina R Antonescu, Alexandre Rouquette, Jean-Michel Coindre, Raf Sciot, Maria Debiec-Rychter
Plexiform fibromyxomas are rare neoplasms, being officially recognized as a distinct entity among benign mesenchymal gastric tumours in the 2010 WHO Classification of Tumours of the Digestive System. Characteristically, these tumours have a multinodular/plexiform growth pattern, and histologically contain variably cellular areas of bland myofibroblastic-type spindle cells embedded in an abundant myxoid matrix, rich in capillary-type vessels. As yet, the molecular and/or genetic features of these tumours are unknown...
July 2016: Journal of Pathology
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