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https://www.readbyqxmd.com/read/28702894/21-gene-recurrence-score-and-locoregional-recurrence-in-lymph-node-negative-estrogen-receptor-positive-breast-cancer
#1
Gulisa Turashvili, Joanne F Chou, Edi Brogi, Monica Morrow, Maura Dickler, Larry Norton, Clifford Hudis, Hannah Y Wen
BACKGROUND/PURPOSE: The 21-gene recurrence score (RS) assay evaluates the likelihood of distant recurrence and benefit of chemotherapy in lymph node-negative, estrogen receptor (ER)-positive, HER2-negative breast cancer patients. The RS categories are associated with the risk of locoregional recurrence (LRR) in some, but not all studies. METHODS: We reviewed the institutional database to identify consecutive female patients with node-negative, ER+/HER2- breast carcinoma tested for the 21-gene RS assay and treated at our center from 2008 to 2013...
July 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28689095/first-dual-ak-gsk-3%C3%AE-inhibitors-endowed-with-antioxidant-properties-as-multifunctional-potential-neuroprotective-agents
#2
Simone Brogi, Anna Ramunno, Lida Savi, Giulia Chemi, Gloria Alfano, Alessandra Pecorelli, Erika Pambianchi, Paola Galatello, Giulia Compagnoni, Federico Focher, Giuseppe Biamonti, Giuseppe Valacchi, Stefania Butini, Sandra Gemma, Giuseppe Campiani, Margherita Brindisi
The manuscript deals with the design, synthesis and biological evaluation of novel benzoxazinone-based and indole-based compounds as multifunctional neuroprotective agents. These compounds inhibit human adenosine kinase (hAK) and human glycogen synthase kinase 3 beta (hGSK-3β) enzymes. Computational analysis based on a molecular docking approach underlined the potential structural requirements for simultaneously targeting both proteins' allosteric sites. In silico hints drove the synthesis of appropriately decorated benzoxazinones and indoles (5a-s, and 6a-c) and biochemical analysis revealed their behavior as allosteric inhibitors of hGSK-3β...
June 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28662998/hematolymphoid-lesions-of-the-breast
#3
REVIEW
Jenny Hoffmann, Robert S Ohgami
Hematolymphoid malignancies of the breast are most commonly neoplasms of mature B-lymphocytes, and may arise as a primary disease or by secondary involvement of a systemic disease. Primary breast lymphomas (PBL) account for 0.04-0.5% of breast malignancies, less than 1% of all non-Hodgkin's lymphomas (NHL), and less than 5% of extranodal lymphomas (Lakhani et al., 2012; Swerdlow et al., 2008; Joks et al., 2011; Barişta et al., 2000; Giardini et al., 1992; Brogi and Harris, 1999; Topalovski et al., 1999).(1-7) Secondary breast lymphomas (SBL) are also rare, with an estimated annual incidence of 0...
May 28, 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28644513/benign-vascular-lesions-of-the-breast-diagnosed-by-core-needle-biopsy-do-not-require-excision
#4
Christopher Sebastiano, Lucas Gennaro, Edi Brogi, Elizabeth Morris, Zenica L Bowser, Cristina R Antonescu, Fresia Pareja, Sandra Brennan, Melissa P Murray
AIMS: Surgical excision of all benign vascular lesions of the breast identified by core needle biopsy has been recommended in the past to rule out a more serious lesion. In this study we investigated the clinical, radiologic, and pathologic findings in patients diagnosed with a benign vascular lesion at our institution to assess whether excision may be spared for lesions without atypia. METHODS AND RESULTS: We searched the electronic medical record for patients with a vascular lesion of the breast diagnosed between 2000 and 2015...
June 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28612228/pleomorphic-lobular-carcinoma-in-situ-of-the-breast-a-single-institution-experience-with-clinical-follow-up-and-centralized-pathology-review
#5
Marina De Brot, Starr Koslow Mautner, Shirin Muhsen, Victor P Andrade, Anita Mamtani, Melissa Murray, Dilip Giri, Rita A Sakr, Edi Brogi, Tari A King
PURPOSE: The natural history of pleomorphic lobular carcinoma in situ (PLCIS) remains largely unknown. METHODS: A pathology database search (1995-2012) was performed to identify patients diagnosed with an LCIS variant. Patients with synchronous breast cancer and/or no evidence of pleomorphism were excluded. Original slides were re-evaluated by three pathologists to identify a consensus cohort of PLCIS. Borderline lesions with focal atypia were classified as LCIS with pleomorphic features (LCIS-PF)...
June 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28577081/the-21-gene-recurrence-score-in-special-histologic-subtypes-of-breast-cancer-with-favorable-prognosis
#6
Gulisa Turashvili, Edi Brogi, Monica Morrow, Clifford Hudis, Maura Dickler, Larry Norton, Hannah Y Wen
BACKGROUND/PURPOSE: The 21-gene recurrence score (RS) assay predicts the likelihood of distant recurrence and chemotherapy benefit in early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. Data on the RS of special histologic subtypes of invasive breast carcinoma with favorable prognosis are limited. METHODS: We reviewed our institutional database to identify patients with special histologic subtypes of breast cancer associated with favorable prognosis and available RS results...
June 3, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28525717/synthesis-and-biological-evaluation-of-novel-neuroprotective-pyridazine-derivatives-as-excitatory-amino-acid-transporter-2-eaat2-activators
#7
Alessia Chelini, Simone Brogi, Marco Paolino, Angela Di Capua, Andrea Cappelli, Gianluca Giorgi, Mersedeh Farzad, Lorenzo Di Cesare Mannelli, Laura Micheli, Carla Ghelardini, Maurizio Anzini
LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the normal clearance of glutamate and providing neuronal protection. Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropathic pain, we synthesized novel activators (4a-f) of EAAT2. Among them 4f, analyzed in comparison with 3 by different paradigms in a rat model of oxaliplatin-induced neuropathic pain, showed the better antihypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy...
May 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28522578/mutated-asxl1-and-number-of-somatic-mutations-as-possible-indicators-of-progression-to-chronic-myelomonocytic-leukemia-of-myelodysplastic-syndromes-with-single-or-multilineage-dysplasia
#8
Ana Valencia-Martinez, Alessandro Sanna, Erico Masala, Elisa Contini, Alice Brogi, Antonella Gozzini, Valeria Santini
No abstract text is available yet for this article.
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28513873/myxoid-fibroadenomas-differ-from-conventional-fibroadenomas-a-hypothesis-generating-study
#9
John R Lozada, Kathleen A Burke, Aoife Maguire, Fresia Pareja, Raymond S Lim, Jisun Kim, Rodrigo Gularte-Merida, Melissa P Murray, Edi Brogi, Britta Weigelt, Jorge S Reis-Filho, Felipe C Geyer
AIMS: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. METHODS AND RESULTS: Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved...
May 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28503546/computational-tool-for-fast-in-silico-evaluation-of-herg-k-channel-affinity
#10
Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Simone Brogi, Stefania Butini, Margherita Brindisi
The development of a novel comprehensive approach for the prediction of hERG activity is herein presented. Software Phase has been used to derive a 3D-QSAR model, employing as alignment rule a common pharmacophore built on a subset of 22 highly active compounds (threshold Ki: 50 nM) against hERG K(+) channel. Five features comprised the pharmacophore: two aromatic rings (R1 and R2), one hydrogen-bond acceptor (A), one hydrophobic site (H), and one positive ionizable function (P). The sequential 3D-QSAR model developed with a set of 421 compounds (randomly divided in training and test set) yielded a test set (Q(2)) = 0...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28431135/reconstitution-of-a-functional-7sk-snrnp
#11
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
#12
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
#13
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
#14
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...
June 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28267263/genetic-analysis-of-uterine-adenosarcomas-and-phyllodes-tumors-of-the-breast
#15
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. PTs 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
#16
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
#17
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
#18
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
#19
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
#20
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
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