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https://www.readbyqxmd.com/read/29739933/recurrent-hotspot-mutations-in-hras-q61-and-pi3k-akt-pathway-genes-as-drivers-of-breast-adenomyoepitheliomas
#1
Felipe C Geyer, Anqi Li, Anastasios D Papanastasiou, Alison Smith, Pier Selenica, Kathleen A Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M Schultheis, Luciano G Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R Lozada, Pedro Blecua, Simone Muenst, Achim A Jungbluth, Maria P Foschini, Hannah Y Wen, Edi Brogi, Juan Palazzo, Brian P Rubin, Charlotte K Y Ng, Larry Norton, Zsuzsanna Varga, Ian O Ellis, Emad A Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S Reis-Filho
Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRASQ61R in non-malignant ER-negative breast epithelial cells with or without a PIK3CAH1047R somatic knock-in results in transformation and the acquisition of the cardinal features of adenomyoepitheliomas, including the expression of myoepithelial markers, a reduction in E-cadherin expression, and an increase in AKT signaling...
May 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29730163/ipsc-derived-neurons-profiling-reveals-gabaergic-circuit-disruption-and-acetylated-%C3%AE-tubulin-defect-which-improves-after-ihdac6-treatment-in-rett-syndrome
#2
Elisa Landucci, Margherita Brindisi, Laura Bianciardi, Lorenza M Catania, Sergio Daga, Susanna Croci, Elisa Frullanti, Chiara Fallerini, Stefania Butini, Simone Brogi, Simone Furini, Riccardo Melani, Angelo Molinaro, Flaminia Clelia Lorenzetti, Valentina Imperatore, Sonia Amabile, Jessica Mariani, Francesca Mari, Francesca Ariani, Tommaso Pizzorusso, Anna Maria Pinto, Flora M Vaccarino, Giuseppe Campiani, Alessandra Renieri, Ilaria Meloni
Mutations in MECP2 gene have been identified in more than 95% of patients with classic Rett syndrome, one of the most common neurodevelopmental disorders in females. Taking advantage of the breakthrough technology of genetic reprogramming, we investigated transcriptome changes in neurons differentiated from induced Pluripotent Stem Cells (iPSCs) derived from patients with different mutations. Profiling by RNA-seq in terminally differentiated neurons revealed a prominent GABAergic circuit disruption along with a perturbation of cytoskeleton dynamics...
May 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29603332/solid-papillary-breast-carcinomas-resembling-the-tall-cell-variant-of-papillary-thyroid-neoplasms-solid-papillary-carcinomas-with-reverse-polarity-harbor-recurrent-mutations-affecting-idh2-and-pik3ca-a-validation-cohort
#3
John R Lozada, Thais Basili, Fresia Pareja, Barbara Alemar, Arnaud C Paula, Rodrigo Gularte-Merida, Dilip D Giri, Patrizia Querzoli, Gabor Cserni, Emad A Rakha, Maria Pia Foschini, Jorge S Reis-Filho, Edi Brogi, Britta Weigelt, Felipe C Geyer
AIMS: Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (BPTC), also known as solid papillary carcinoma with reverse polarity, is a rare histologic type of breast cancer that morphologically resembles the tall cell variant of papillary thyroid carcinoma. BPTCs are characterized by IDH2 R172 hotspot somatic mutations or mutually exclusive TET2 somatic mutations, concurrently with mutations affecting PI3K pathway-related genes. We sought to characterize their histology, and investigate the frequency of IDH2 and PIK3CA mutations in an independent cohort of BPTCs, as well as in conventional solid papillary carcinomas (SPCs)...
March 30, 2018: Histopathology
https://www.readbyqxmd.com/read/29577795/regional-citrate-calcium-anticoagulation-during-polymyxin-b-hemoperfusion-a-case-series
#4
Francesco Forfori, Etrusca Brogi, Anna Sidoti, Martina Giraudini, Gianpaola Monti, Nadia Zarrillo, Vincenzo Cantaluppi, Claudio Ronco
INTRODUCTION: So far, only heparin-based anticoagulation has been proposed during polymyxin-B hemoperfusion. However, postsurgical septic patients can be at high risk of bleeding due to either surgical complications or septic coagulation derangement. Consequently, heparin should not represent in some cases the anticoagulation regimen of choice in this type of patients. METHODS AND RESULTS: We present a case series of four postsurgical septic patients treated with polymyxin-B hemoperfusion using regional citrate anticoagulation...
March 1, 2018: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/29571157/antimalarial-agents-against-both-sexual-and-asexual-parasites-stages-structure-activity-relationships-and-biological-studies-of-the-malaria-box-compound-1-5-4-bromo-2-chlorophenyl-furan-2-yl-n-piperidin-4-yl-methyl-methanamine-mmv019918-and-analogues
#5
Alessandra Vallone, Sarah D'Alessandro, Simone Brogi, Margherita Brindisi, Giulia Chemi, Gloria Alfano, Stefania Lamponi, Soon Goo Lee, Joseph M Jez, Karin J M Koolen, Koen J Dechering, Simona Saponara, Fabio Fusi, Beatrice Gorelli, Donatella Taramelli, Silvia Parapini, Reto Caldelari, Giuseppe Campiani, Sandra Gemma, Stefania Butini
Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P...
March 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29535827/severe-hypoxia-selects-hematopoietic-progenitors-with-stem-cell-potential-from-primary-myelodysplastic-syndrome-bone-marrow-cell-cultures
#6
Erico Masala, Ana Valencia-Martinez, Serena Pillozzi, Tommaso Rondelli, Alice Brogi, Alessandro Sanna, Antonella Gozzini, Annarosa Arcangeli, Persio Dello Sbarba, Valeria Santini
Myelodysplastic Syndromes (MDS) are clonal neoplasms where stem/progenitor cells endowed with self-renewal and capable of perpetuating the disease have been demonstrated. It is known that oxygen tension plays a key role in driving normal hematopoiesis and that hematopoietic stem cells are maintained in hypoxic areas of the bone marrow (BM). Hypoxia could also regulate leukemic/dysplastic hematopoiesis. We evaluated the stem cell potential of MDS cells derived from the BM of 39 MDS patients and selected under severe hypoxia...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29520654/the-21-gene-recurrence-score-in-male-breast-cancer
#7
Gulisa Turashvili, Monica Gonzalez-Loperena, Edi Brogi, Maura Dickler, Larry Norton, Monica Morrow, Hannah Y Wen
BACKGROUND: Given the limited data, systemic treatment of male breast cancer has been extrapolated from female patients. The 21-gene recurrence score (RS) assay estimates the risk of distant recurrence and chemotherapy benefit in early-stage, ER+/HER2- female breast cancer. We assessed the association between RS and type of treatment in male breast cancer. METHODS: We identified male patients with ER+/HER2- breast cancer and available RS results treated at our institution in 2006-2016...
June 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29451794/-s-2-amino-3-5-methyl-3-hydroxyisoxazol-4-yl-propanoic-acid-ampa-and-kainate-receptor-ligands-further-exploration-of-bioisosteric-replacements-and-structural-and-biological-investigation
#8
Simone Brogi, Margherita Brindisi, Stefania Butini, Giridhar U Kshirsagar, Samuele Maramai, Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Ettore Novellino, Paolo Fiorenzani, Jessica Pinassi, Anna Maria Aloisi, Mikko Gynther, Raminta Venskutonytė, Liwei Han, Karla Frydenvang, Jette Sandholm Kastrup, Darryl S Pickering
Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
March 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29438245/-a-message-in-the-bottle
#9
Luigi Vetrugno, Etrusca Brogi, Federico Barbariol, Francesco Forfori, Elena Bignami
No abstract text is available yet for this article.
March 2018: Anesthesiology
https://www.readbyqxmd.com/read/29426205/optical-and-molecular-characterization-of-dissolved-organic-matter-dom-in-the-arctic-ice-core-and-the-underlying-seawater-cambridge-bay-canada-implication-for-increased-autochthonous-dom-during-ice-melting
#10
Simona Retelletti Brogi, Sun-Yong Ha, Kwanwoo Kim, Morgane Derrien, Yun Kyung Lee, Jin Hur
Sea ice contains a large amount of dissolved organic matter (DOM), which can be released into the ocean once it melts. In this study, Arctic sea ice DOM was characterized for its optical (fluorescence) properties as well as the molecular sizes and composition via size exclusion chromatography and Fourier transformation ion cyclotron resonance mass spectrometry (FT-ICR MS). Ice cores were collected along with the underlying seawater samples in Cambridge Bay, an Arctic area experiencing seasonal ice formation...
June 15, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29413653/lobular-carcinoma-in-situ
#11
REVIEW
Hannah Y Wen, Edi Brogi
Lobular carcinoma in situ (LCIS) is a risk factor and a nonobligate precursor of breast carcinoma. The relative risk of invasive carcinoma after classic LCIS diagnosis is approximately 9 to 10 times that of the general population. Classic LCIS diagnosed on core biopsy with concordant imaging and pathologic findings does not mandate surgical excision, and margin status is not reported. The identification of variant LCIS in a needle core biopsy specimen mandates surgical excision, regardless of radiologic-pathologic concordance...
March 2018: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/29334428/development-of-potent-inhibitors-of-the-mycobacterium-tuberculosis-virulence-factor-zmp1-and-evaluation-of-their-effect-on-mycobacterial-survival-inside-macrophages
#12
Marco Paolino, Margherita Brindisi, Alessandra Vallone, Stefania Butini, Giuseppe Campiani, Chiara Nannicini, Germano Giuliani, Maurizio Anzini, Stefania Lamponi, Gianluca Giorgi, Diego Sbardella, Davide M Ferraris, Stefano Marini, Massimo Coletta, Ivana Palucci, Mariachiara Minerva, Giovanni Delogu, Ilaria Pepponi, Delia Goletti, Andrea Cappelli, Sandra Gemma, Simone Brogi
The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N-(benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site...
March 6, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29304773/breast-carcinoma-with-21-gene-recurrence-score-lower-than-18-rate-of-locoregional-recurrence-in-a-large-series-with-clinical-follow-up
#13
Gulisa Turashvili, Edi Brogi, Monica Morrow, Maura Dickler, Larry Norton, Clifford Hudis, Hannah Y Wen
BACKGROUND: The 21-gene recurrence score (RS) assay determines the benefit of adding chemotherapy to endocrine therapy for patients with early stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. The RS risk groups predict the likelihood of distant recurrence and have recently been associated with an increased risk of locoregional recurrence (LRR). This study analyzed clinicopathologic features of patients with low RS and LRR. METHODS: In our institutional database, we identified 1396 consecutive female patients with lymph node negative, ER+/HER2- invasive breast carcinoma and low RS (<18) results, treated at our center from 2008 to 2013...
January 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29282107/thoracic-ultrasound-for-pleural-effusion-in-the-intensive-care-unit-a-narrative-review-from-diagnosis-to-treatment
#14
REVIEW
E Brogi, L Gargani, E Bignami, F Barbariol, A Marra, F Forfori, L Vetrugno
Pleural effusion (PLEFF), mostly caused by volume overload, congestive heart failure, and pleuropulmonary infection, is a common condition in critical care patients. Thoracic ultrasound (TUS) helps clinicians not only to visualize pleural effusion, but also to distinguish between the different types. Furthermore, TUS is essential during thoracentesis and chest tube drainage as it increases safety and decreases life-threatening complications. It is crucial not only during needle or tube drainage insertion, but also to monitor the volume of the drained PLEFF...
December 28, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29276709/tumor-heterogeneity-in-breast-cancer
#15
REVIEW
Gulisa Turashvili, Edi Brogi
Breast cancer is a heterogeneous disease and differs greatly among different patients (intertumor heterogeneity) and even within each individual tumor (intratumor heterogeneity). Clinical and morphologic intertumor heterogeneity is reflected by staging systems and histopathologic classification of breast cancer. Heterogeneity in the expression of established prognostic and predictive biomarkers, hormone receptors, and human epidermal growth factor receptor 2 oncoprotein is the basis for targeted treatment. Molecular classifications are indicators of genetic tumor heterogeneity, which is probed with multigene assays and can lead to improved stratification into low- and high-risk groups for personalized therapy...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29219544/energy-spectrum-of-cosmic-ray-electron-and-positron-from-10-gev-to-3-tev-observed-with-the-calorimetric-electron-telescope-on-the-international-space-station
#16
O Adriani, Y Akaike, K Asano, Y Asaoka, M G Bagliesi, G Bigongiari, W R Binns, S Bonechi, M Bongi, P Brogi, J H Buckley, N Cannady, G Castellini, C Checchia, M L Cherry, G Collazuol, V Di Felice, K Ebisawa, H Fuke, T G Guzik, T Hams, M Hareyama, N Hasebe, K Hibino, M Ichimura, K Ioka, W Ishizaki, M H Israel, A Javaid, K Kasahara, J Kataoka, R Kataoka, Y Katayose, C Kato, N Kawanaka, Y Kawakubo, H S Krawczynski, J F Krizmanic, S Kuramata, T Lomtadze, P Maestro, P S Marrocchesi, A M Messineo, J W Mitchell, S Miyake, K Mizutani, A A Moiseev, K Mori, M Mori, N Mori, H M Motz, K Munakata, H Murakami, S Nakahira, J Nishimura, G A de Nolfo, S Okuno, J F Ormes, S Ozawa, L Pacini, F Palma, P Papini, A V Penacchioni, B F Rauch, S B Ricciarini, K Sakai, T Sakamoto, M Sasaki, Y Shimizu, A Shiomi, R Sparvoli, P Spillantini, F Stolzi, I Takahashi, M Takayanagi, M Takita, T Tamura, N Tateyama, T Terasawa, H Tomida, S Torii, Y Tsunesada, Y Uchihori, S Ueno, E Vannuccini, J P Wefel, K Yamaoka, S Yanagita, A Yoshida, K Yoshida, T Yuda
First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV is presented based upon observations with the CALET instrument on the International Space Station starting in October, 2015. Nearly a half million electron and positron events are included in the analysis. CALET is an all-calorimetric instrument with total vertical thickness of 30 X_{0} and a fine imaging capability designed to achieve a large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum over 30 GeV can be fit with a single power law with a spectral index of -3...
November 3, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29131552/activation-of-the-wnt-pathway-by-small-peptides-rational-design-synthesis-and-biological-evaluation
#17
Simone Brogi, Samuele Maramai, Margherita Brindisi, Giulia Chemi, Valentina Porcari, Claudio Corallo, Luigi Gennari, Ettore Novellino, Anna Ramunno, Stefania Butini, Giuseppe Campiani, Sandra Gemma
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with the Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides. These compounds behave as agonists of the canonical Wnt pathway in the micromolar range when tested on a dual luciferase Wnt functional assay in glioblastoma cells. Two of the oligopeptides showed a lack of cytotoxicity in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knees of elderly patients)...
December 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29092578/hermite-regularization-of-the-lattice-boltzmann-method-for-open-source-computational-aeroacoustics
#18
F Brogi, O Malaspinas, B Chopard, C Bonadonna
The lattice Boltzmann method (LBM) is emerging as a powerful engineering tool for aeroacoustic computations. However, the LBM has been shown to present accuracy and stability issues in the medium-low Mach number range, which is of interest for aeroacoustic applications. Several solutions have been proposed but are often too computationally expensive, do not retain the simplicity and the advantages typical of the LBM, or are not described well enough to be usable by the community due to proprietary software policies...
October 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/29043292/phyllodes-tumors-with-and-without-fibroadenoma-like-areas-display-distinct-genomic-features-and-may-evolve-through-distinct-pathways
#19
Fresia Pareja, Felipe C Geyer, Rahul Kumar, Pier Selenica, Salvatore Piscuoglio, Charlotte K Y Ng, Kathleen A Burke, Marcia Edelweiss, Melissa P Murray, Edi Brogi, Britta Weigelt, Jorge S Reis-Filho
Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29030772/diagnostics-of-anti-mag-antibody-polyneuropathy
#20
REVIEW
Diego Franciotta, Matteo Gastaldi, Luana Benedetti, Martina Garnero, Tiziana Biagioli, Marco Brogi, Gianna Costa, Elisabetta Fadda, Francesca Andreetta, Ornella Simoncini, Claudia Giannotta, Elena Bazzigaluppi, Raffaella Fazio, Roberta Bedin, Diana Ferraro, Sara Mariotto, Sergio Ferrari, Elisabetta Galloni, Valentina De Riva, Elisabetta Zardini, Andrea Cortese, Eduardo Nobile-Orazio
This document presents the guidelines for anti-myelin-associated glycoprotein (MAG) antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses. The main clinical information on anti-MAG antibody polyneuropathy, indications and limits of anti-MAG antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists...
October 2017: Neurological Sciences
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