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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...
October 20, 2016: Journal of Obstetrics and Gynaecology Research
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
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)...
October 18, 2016: Neurological Sciences
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
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
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...
September 23, 2016: A & A Case Reports
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
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 Comen, Elizabeth A Morris, Alan Kotin, Edi Brogi, Y Hannah Wen, Monica Morrow, Mario E Lacouture, Padmanee Sharma, James P Allision, Clifford A Hudis, Jedd D Wolchok, Larry Norton
PURPOSE: To assess the safety and tolerability of pre-operative 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 pre-operative tumor cryoablation (n=7), single-dose ipilimumab at 10mg/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...
August 26, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
Robert A Soslow, Edi Brogi
No abstract text is available yet for this article.
August 11, 2016: American Journal of Surgical Pathology
Hannah Y Wen, Melissa Krystel-Whittemore, Sujata Patil, Fresia Pareja, Zenica L Bowser, Maura N Dickler, Larry Norton, Monica Morrow, Clifford A Hudis, Edi Brogi
BACKGROUND: A 21-gene expression assay (Oncotype DX recurrence score [RS]) that uses reverse transcriptase-polymerase chain reaction is used clinically in patients with early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinoma (ER+/HER2- BC) to determine both prognosis with tamoxifen therapy and the usefulness of adding adjuvant chemotherapy. Use of the assay is associated with reductions in overall chemotherapy use. The current study examined the treatments and outcomes in patients with low RS...
August 15, 2016: Cancer
Aoife Maguire, Edi Brogi
CONTEXT: -Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy...
August 2016: Archives of Pathology & Laboratory Medicine
Pau Castel, Haley Ellis, Ruzica Bago, Eneda Toska, Pedram Razavi, F Javier Carmona, Srinivasaraghavan Kannan, Chandra S Verma, Maura Dickler, Sarat Chandarlapaty, Edi Brogi, Dario R Alessi, José Baselga, Maurizio Scaltriti
PIK3CA, which encodes the p110α subunit of PI3K, is frequently mutated and oncogenic in breast cancer. PI3Kα inhibitors are in clinical development and despite promising early clinical activity, intrinsic resistance is frequent among patients. We have previously reported that residual downstream mTORC1 activity upon treatment with PI3Kα inhibitors drives resistance to these agents. However, the mechanism underlying this phenotype is not fully understood. Here we show that in cancer cells resistant to PI3Kα inhibition, PDK1 blockade restores sensitivity to these therapies...
August 8, 2016: Cancer Cell
Hua Gao, Goutam Chakraborty, Zhanguo Zhang, Intissar Akalay, Mayur Gadiya, Yaquan Gao, Surajit Sinha, Jian Hu, Cizhong Jiang, Muzaffar Akram, Edi Brogi, Birgit Leitinger, Filippo G Giancotti
Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCα. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain...
June 30, 2016: Cell
Fresia Pareja, Adriana D Corben, Sandra B Brennan, Melissa P Murray, Zenica L Bowser, Kiran Jakate, Christopher Sebastiano, Monica Morrow, Elizabeth A Morris, Edi Brogi
BACKGROUND: The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core-needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC). METHODS: This study identified women with a CNB diagnosis of intraductal papilloma without atypia or carcinoma at a cancer center between 2003 and 2013. Radiologic-pathologic concordance was assessed for all cases, and discordant cases were excluded...
September 15, 2016: Cancer
Etrusca Brogi, Roy Kazan, Shantale Cyr, Francesco Giunta, Thomas M Hemmerling
PURPOSE: The transversus abdominal plane (TAP) block has been described as an effective pain control technique after abdominal surgery. We performed a systematic review and meta-analysis of randomized-controlled trials (RCTs) to account for the increasing number of TAP block studies appearing in the literature. The primary outcome we examined was the effect of TAP block on the postoperative pain score at six, 12, and 24 hr. The secondary outcome was 24-hr morphine consumption. SOURCE: We searched the United States National Library of Medicine database, the Excerpta Medica database, and the Cochrane Central Register of Controlled Clinical Studies and identified RCTs focusing on the analgesic efficacy of TAP block compared with a control group [i...
October 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
S Butini, K Nikolic, S Kassel, H Brückmann, S Filipic, D Agbaba, S Gemma, S Brogi, M Brindisi, G Campiani, H Stark
Most neurological diseases have a multifactorial nature and the number of molecular mechanisms discovered as underpinning these diseases is continuously evolving. The old concept of developing selective agents for a single target does not fit with the medical need of most neurological diseases. The development of designed multiple ligands holds great promises and appears as the next step in drug development for the treatment of these multifactorial diseases. Dopamine and its five receptor subtypes are intimately involved in numerous neurological disorders...
July 2016: Progress in Neurobiology
Anup Sood, Alexandra M Miller, Edi Brogi, Yunxia Sui, Joshua Armenia, Elizabeth McDonough, Alberto Santamaria-Pang, Sean Carlin, Aleksandra Stamper, Carl Campos, Zhengyu Pang, Qing Li, Elisa Port, Thomas G Graeber, Nikolaus Schultz, Fiona Ginty, Steven M Larson, Ingo K Mellinghoff
The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins at the single-cell level in formalin-fixed and paraffin-embedded samples from treatment-naive stage II/III human breast cancer. Unsupervised clustering of protein expression data from 638,577 tumor cells in 26 breast cancers identified 8 clusters of protein coexpression...
May 5, 2016: JCI Insight
Margherita Brindisi, Samuele Maramai, Simone Brogi, Emanuela Fanigliulo, Stefania Butini, Egeria Guarino, Alice Casagni, Stefania Lamponi, Claudia Bonechi, Seema M Nathwani, Federica Finetti, Francesco Ragonese, Paola Arcidiacono, Pietro Campiglia, Salvatore Valenti, Ettore Novellino, Roberta Spaccapelo, Lucia Morbidelli, Daniela M Zisterer, Clive D Williams, Alessandro Donati, Cosima Baldari, Giuseppe Campiani, Cristina Ulivieri, Sandra Gemma
Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel. Starting from these peptide-hits, we herein describe the synthesis and the biological investigation of linear and cyclic peptides structurally related to PEP2. While linear peptides (2a,b, 3a,b, 4, 6a-f) were found inactive in cell-based assays, biological analysis revealed a pro-apoptotic effect for most of the cyclic peptides (5a-g)...
July 19, 2016: European Journal of Medicinal Chemistry
Margherita Brindisi, Simone Brogi, Simone Giovani, Sandra Gemma, Stefania Lamponi, Filomena De Luca, Ettore Novellino, Giuseppe Campiani, Jean-Denis Docquier, Stefania Butini
Metallo-β-lactamases (MBLs) represent one of the most important and widespread mechanisms of resistance to β-lactam antibiotics (including the life-saving carbapenems), against which no clinically useful inhibitors are currently available. We report herein a structure-based high-throughput docking (HTD) campaign on three clinically-relevant acquired MBLs (IMP-1, NDM-1 and VIM-2). The initial hit NF1810 (1) was optimized providing the broad-spectrum inhibitor 3i, which is able to potentiate the in vitro activity of cefoxitin on a VIM-2-producing E...
April 28, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
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