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https://www.readbyqxmd.com/read/28431135/reconstitution-of-a-functional-7sk-snrnp
#1
John E Brogie, David H Price
The 7SK small nuclear ribonucleoprotein (snRNP) plays a central role in RNA polymerase II elongation control by regulating the availability of active P-TEFb. We optimized conditions for analyzing 7SK RNA by SHAPE and demonstrated a hysteretic effect of magnesium on 7SK folding dynamics including a 7SK GAUC motif switch. We also found evidence that the 5΄ end pairs alternatively with two different regions of 7SK giving rise to open and closed forms that dictate the state of the 7SK motif. We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE to reconstruct a functional 7SK snRNP in vitro...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28299887/fibroepithelial-lesions-in-the-breast-of-adolescent-females-a-clinicopathological-study-of-54-cases
#2
Dara S Ross, Dilip D Giri, Muzaffar M Akram, Jeffrey P Catalano, Cristina Olcese, Kimberly J Van Zee, Edi Brogi
Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records...
March 2017: Breast Journal
https://www.readbyqxmd.com/read/28299848/specimen-identification-errors-in-breast-biopsies-age-matters-report-of-two-near-miss-events-and-review-of-the-literature
#3
Gary Tozbikian, Mary L Gemignani, Edi Brogi
The consequences of patient identification errors due to specimen mislabeling can be deleterious. We describe two near-miss events involving mislabeled breast specimens from two patients who sought treatment at our institution. In both cases, microscopic review of the slides identified inconsistencies between the histologic findings and patient age, unveiling specimen identification errors. By correlating the clinical information with the microscopic findings, we identified mistakes that had occurred at the time of specimen accessioning at the original laboratories...
March 16, 2017: Breast Journal
https://www.readbyqxmd.com/read/28299801/bi-allelic-alterations-in-dna-repair-genes-underpin-homologous-recombination-dna-repair-defects-in-breast-cancer
#4
Robert W Mutter, Nadeem Riaz, Charlotte Ky Ng, Rob Delsite, Salvatore Piscuoglio, Marcia Edelweiss, Luciano G Martelotto, Rita A Sakr, Tari A King, Dilip D Giri, Maria Drobnjak, Edi Brogi, Ranjit Bindra, Giana Bernheim, Raymond S Lim, Pedro Blecua, Alexis Desrichard, Dan Higginson, Russell Towers, Ruomu Jiang, William Lee, Britta Weigelt, Jorge S Reis-Filho, Simon N Powell
Homologous recombination (HR) DNA repair-deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51-based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole-exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large-scale state transitions and specific mutational signatures...
March 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28267263/genetic-analysis-of-uterine-adenosarcomas-and-phyllodes-tumors-of-the-breast
#5
Felipe C Geyer, Kathleen A Burke, Salvatore Piscuoglio, Charlotte K Y Ng, Anastasios D Papanastasiou, Caterina Marchiò, Pier Selenica, Marcia Edelweiss, Melissa P Murray, Edi Brogi, Robert A Soslow, Brian P Rubin, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Uterine adenosarcomas and breast phyllodes tumors (PTs) are morphologically similar, being composed of stromal projections in a leaf-like fashion lined by epithelial cells. Here we investigated whether their histologic similarities would be mirrored at the genetic level. The previously reported repertoires of somatic genetic alterations found in 19 adenosarcomas and 22 PTs (six benign, six borderline and 10 malignant) were compared. Phyllodes tumors significantly more frequently displayed mutations affecting MED12, the TERT gene promoter and bona fide cancer genes; whereas adenosarcomas harbored a higher rate of MDM2/CDK4 and TERT gene amplifications...
March 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28207458/response-to-influence-of-mechanical-mentilation-on-the-incidence-of-pneumothorax-during-infraclavicular-subclavian-vein-catheterization-a-prospective-randomized-noninferiority-trial
#6
Etrusca Brogi, Giampaolo Martinelli, Francesco Forfori
No abstract text is available yet for this article.
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28160237/management-of-patients-presenting-with-haemoptysis-to-a-tertiary-care-italian-emergency-department-the-florence-haemoptysis-score-flhasc
#7
Simone Vanni, Simone Bianchi, Sofia Bigiarini, Claudia Casula, Marco Brogi, Stefano Orsi, Manlio Acquafresca, Lorenzo Corbetta, Stefano Grifoni
We analysed the clinical features and diagnostic workup of patients presenting with haemoptysis to an Italian teaching hospital to derive an easy-to-use clinical score to guide risk stratification and initial management in the emergency department (ED). We retrospectively reviewed clinical records of consecutive patients with haemoptysis over 1 year. A pre-specified set of variables, including demographic data, vital signs, type of expectorate (pure blood vs. blood-streaked sputum), comorbidities, and diagnostic tests and treatments was originally registered...
February 3, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/27928699/estimating-the-oncotypedx-score-validation-of-an-inexpensive-estimation-tool
#8
Anne A Eaton, Catherine E Pesce, James O Murphy, Michelle M Stempel, Sujata M Patil, Edi Brogi, Clifford A Hudis, Mahmoud El-Tamer
BACKGROUND: OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score. METHODS: Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#9
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
January 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27913435/idh2-mutations-define-a-unique-subtype-of-breast-cancer-with-altered-nuclear-polarity
#10
Sarah Chiang, Britta Weigelt, Huei-Chi Wen, Fresia Pareja, Ashwini Raghavendra, Luciano G Martelotto, Kathleen A Burke, Thais Basili, Anqi Li, Felipe C Geyer, Salvatore Piscuoglio, Charlotte K Y Ng, Achim A Jungbluth, Jörg Balss, Stefan Pusch, Gabrielle M Baker, Kimberly S Cole, Andreas von Deimling, Julie M Batten, Jonathan D Marotti, Hwei-Choo Soh, Benjamin L McCalip, Jonathan Serrano, Raymond S Lim, Kalliopi P Siziopikou, Song Lu, Xiaolong Liu, Tarek Hammour, Edi Brogi, Matija Snuderl, A John Iafrate, Jorge S Reis-Filho, Stuart J Schnitt
Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27842893/identification-of-novel-fluorescent-probes-preventing-prp-sc-replication-in-prion-diseases
#11
Ludovica Zaccagnini, Simone Brogi, Margherita Brindisi, Sandra Gemma, Giulia Chemi, Giuseppe Legname, Giuseppe Campiani, Stefania Butini
Prion diseases are serious, not curable neurodegenerative disorders caused by the accumulation of the misfolded protein PrP(Sc) that represents the pathological variant of the normally folded cellular protein PrP(C). Molecules that bind the cellular isoform PrP(C) preventing its misfolding, could arrest the progression of pathological conditions related to the abnormal PrP protein. In this context, by combining 3D-QSAR model, derived from pharmacophore-based alignment, with molecular docking procedures and physico-chemical properties prediction we have developed a virtual screening protocol to find novel chemicals able to prevent PrP(C) misfolding...
February 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27762467/immunoglobulin-m-indirect-fluorescent-antibody-test-for-the-diagnosis-of-acute-toxoplasmosis-during-pregnancy-in-the-avidity-era-a-14-year-experience-at-the-tuscany-reference-center-for-infectious-diseases-in-pregnancy-florence-italy
#12
Michele Trotta, Beatrice Borchi, Lorenzo Zammarchi, Gaetana Sterrantino, Michela Brogi, Seble Tekle Kiros, Chiara Lorini, Guglielmo Bonaccorsi, Maria Grazia Colao, Alessandro Bartoloni
AIM: The aim of this study was to evaluate immunoglobulin M indirect-fluorescent antibody test (IgM IFAT) for the diagnosis of acute or chronic Toxoplasma infection in pregnancy. METHODS: Pregnant women with suspected acute toxoplasmosis referred to the Tuscany Reference Center for Infectious Diseases in Pregnancy during the period 1998-2012 were retrospectively enrolled. All women were tested with a panel of serological tests, including enzyme-linked immunosorbent assay for IgG avidity and IgM IFAT...
December 2016: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/27761108/dopamine-d3-receptor-antagonists-as-potential-therapeutics-for-the-treatment-of-neurological-diseases
#13
Samuele Maramai, Sandra Gemma, Simone Brogi, Giuseppe Campiani, Stefania Butini, Holger Stark, Margherita Brindisi
D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27757552/safety-and-tolerability-of-fingolimod-in-patients-with-relapsing-remitting-multiple-sclerosis-results-of-an-open-label-clinical-trial-in-italy
#14
Alice Laroni, Davide Brogi, Vincenzo Brescia Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni Luigi Mancardi
The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs)...
January 2017: Neurological Sciences
https://www.readbyqxmd.com/read/27701165/lung-ultrasound-pattern-is-normal-during-the-last-gestational-weeks-an-observational-pilot-study
#15
Erik Arbeid, Alessio Demi, Etrusca Brogi, Elisa Gori, Teresa Giusto, Gino Soldati, Luigi Vetrugno, Francesco Giunta, Francesco Forfori
BACKGROUND/AIMS: The normal lung ultrasound (US) pattern during a regular pregnancy has not been evaluated extensively in the current literature. Pregnancy-related changes in the respiratory tract affect maternal predisposition to several respiratory complications; consequently, it is important to differentiate between a physiologic pattern during pregnancy and a pathologic lung pattern, due to respiratory failure. The goal of our study was to assess the normal US lung pattern in women without known comorbidities in the last weeks of pregnancy...
October 5, 2016: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/27675928/mre11-dysfunction-is-associated-with-triple-negative-breast-cancer-and-confers-sensitivity-to-dna-damaging-therapy
#16
G P Gupta, A Y Ho, W Feng, C Fan, M Akram, E Brogi, S N Powell, C M Perou, Y H Wen, J H J Petrini
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27669028/polymyxin-b-direct-hemoperfusion-using-regional-citrate-calcium-anticoagulation-a-case-report
#17
Anna Sidoti, Etrusca Brogi, Joshua Morse, Michele Collareta, Luigi Vetrugno, Francesco Giunta, Francesco Forfori
Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP...
December 1, 2016: A & A Case Reports
https://www.readbyqxmd.com/read/27587469/deep-sequencing-of-t-cell-receptor-dna-as-a-biomarker-of-clonally-expanded-tils-in-breast-cancer-after-immunotherapy
#18
David B Page, Jianda Yuan, David Redmond, Y Hanna Wen, Jeremy C Durack, Ryan Emerson, Stephen Solomon, Zhiwan Dong, Phillip Wong, Christopher Comstock, Adi Diab, Janice Sung, Majid Maybody, Elizabeth Morris, Edi Brogi, Monica Morrow, Virgilio Sacchini, Olivier Elemento, Harlan Robins, Sujata Patil, James P Allison, Jedd D Wolchok, Clifford Hudis, Larry Norton, Heather L McArthur
In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti-CTLA-4 (ipilimumab), or cryoablation + ipilimumab...
October 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27566765/a-pilot-study-of-preoperative-single-dose-ipilimumab-and-or-cryoablation-in-women-with-early-stage-breast-cancer-with-comprehensive-immune-profiling
#19
Heather L McArthur, Adi Diab, David B Page, Jianda Yuan, Stephen B Solomon, Virgilio Sacchini, Christopher Comstock, Jeremy C Durack, Majid Maybody, Janice Sung, Arielle Ginsberg, Phillip Wong, Afsar Barlas, Zhiwan Dong, Chunjun Zhao, Brian Blum, Sujata Patil, Deirdre Neville, Elizabeth A Comen, Elizabeth A Morris, Alan Kotin, Edi Brogi, Y Hannah Wen, Monica Morrow, Mario E Lacouture, Padmanee Sharma, James P Allison, Clifford A Hudis, Jedd D Wolchok, Larry Norton
PURPOSE: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. EXPERIMENTAL DESIGN: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27556815/phenylpyrrole-based-hdac-inhibitors-synthesis-molecular-modeling-and-biological-studies
#20
Margherita Brindisi, Caterina Cavella, Simone Brogi, Angela Nebbioso, Johanna Senger, Samuele Maramai, Alfonso Ciotta, Concetta Iside, Stefania Butini, Stefania Lamponi, Ettore Novellino, Lucia Altucci, Manfred Jung, Giuseppe Campiani, Sandra Gemma
AIM: Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in the initiation and progression of cancer. Currently, three hydroxamate-containing HDAC pan-inhibitors have been approved as antitumor agents. RESULTS: We herein present the development of a series of novel phenylpyrrole-based derivatives stemmed from combined computational and medicinal chemistry efforts to rationally modulate HDAC1/6 isoform selectivity. In vitro activity on HDAC1 and HDAC6 isoforms and the effects of selected analogs on histone H3 and α-tubulin acetylation levels were determined...
September 2016: Future Medicinal Chemistry
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