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https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#1
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28101746/music-preferences-friendship-and-externalizing-behavior-in-early-adolescence-a-siena-examination-of-the-music-marker-theory-using-the-snare-study
#2
Aart Franken, Loes Keijsers, Jan Kornelis Dijkstra, Tom Ter Bogt
Music Marker Theory posits that music is relevant for the structuring of peer groups and that rock, urban, or dance music preferences relate to externalizing behavior. The present study tested these hypotheses, by investigating the role of music preference similarity in friendship selection and the development of externalizing behavior, while taking the effects of friends' externalizing behavior into account. Data were used from the first three waves of the SNARE (Social Network Analysis of Risk behavior in Early adolescence) study (N = 1144; 50% boys; M age = 12...
January 18, 2017: Journal of Youth and Adolescence
https://www.readbyqxmd.com/read/28099737/decreased-rates-of-shoulder-dystocia-and-brachial-plexus-injury-via-an-evidence-based-practice-bundle
#3
Laura E Sienas, Herman L Hedriana, Suzanne Wiesner, Barbara Pelletreau, Machelle D Wilson, Laurence E Shields
OBJECTIVE: To evaluate whether a standardized approach to identify pregnant women at risk for shoulder dystocia (SD) is associated with reduced incidence of SD and brachial plexus injury (BPI). METHODS: Between 2011 and 2015, prospective data were collected from 29 community-based hospitals in the USA during implementation of an evidence-based practice bundle, including an admission risk assessment, required "timeout" before operative vaginal delivery (OVD), and low-fidelity SD drills...
February 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28096270/mutation-enrichment-next-generation-sequencing-for-quantitative-detection-of-kras-mutations-in-urine-cell-free-dna-from-patients-with-advanced-cancers
#4
Takeo Fujii, Afsaneh Barzi, Andrea Sartore-Bianchi, Andrea Cassingena, Giulia Siravegna, Daniel Karp, Sarina Piha-Paul, Vivek Subbiah, Apostolia M Tsimberidou, Helen Huang, Sillvio Veronese, Federica Di Nicolantonio, Sandeep C Pingle, Cecile Rose T Vibat, Saege Hancock, David Berz, Vladislava O Melnikova, Mark G Erlander, Rajyalakshmi Luthra, Scott Kopetz, Funda Meric-Bernstam, Salvatore Siena, Heinz-Josef Lenz, Alberto Bardelli, Filip Janku
PURPOSE: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers non-invasive biologic material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS. EXPERIMENTAL DESIGN: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed and results were compared to clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28061143/perceptions-of-public-breastfeeding-images-and-their-association-with-breastfeeding-knowledge-and-attitudes-among-an-internet-panel-of-men-ages-21-44-in-the-united-states
#5
Brianna M Magnusson, Callie R Thackeray, Sarah A Van Wagenen, Siena F Davis, Rickelle Richards, Ray M Merrill
BACKGROUND: Men's attitudes toward public breastfeeding may influence a woman's decisions about breastfeeding and her perceived comfort with public breastfeeding. Research aim: This study aimed to evaluate factors associated with men's visual perception of images of public breastfeeding. METHODS: A 95-item online survey was administered to 502 U.S. men ages 21 to 44. Respondents were presented with four images of women breastfeeding and asked to evaluate agreement with 15 adjectives describing each image...
February 2017: Journal of Human Lactation: Official Journal of International Lactation Consultant Association
https://www.readbyqxmd.com/read/28017438/the-role-of-vaccines-and-vaccine-decision-making-to-achieve-the-goals-of-the-grand-convergence-in-public-health
#6
David C Kaslow, Jorge Kalil, David Bloom, Gianluca Breghi, Anna Maria Colucci, Ennio De Gregorio, Guru Madhavan, Genevieve Meier, Richard Seabrook, Xiaoning Xu
On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity...
December 22, 2016: Vaccine
https://www.readbyqxmd.com/read/27998236/randomized-phase-ii-trial-of-seribantumab-in-combination-with-paclitaxel-in-patients-with-advanced-platinum-resistant-or-refractory-ovarian-cancer
#7
Joyce F Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria Del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R Wendel Naumann, Robert L Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27997874/digital-pcr-assessment-of-mgmt-promoter-methylation-coupled-with-reduced-protein-expression-optimises-prediction-of-response-to-alkylating-agents-in%C3%A2-metastatic-colorectal-cancer-patients
#8
Andrea Sartore-Bianchi, Filippo Pietrantonio, Alessio Amatu, Massimo Milione, Andrea Cassingena, Silvia Ghezzi, Marta Caporale, Rosa Berenato, Chiara Falcomatà, Alessio Pellegrinelli, Alberto Bardelli, Michele Nichelatti, Federica Tosi, Filippo De Braud, Federica Di Nicolantonio, Ludovic Barault, Salvatore Siena
BACKGROUND: O(6)-methylguanine-DNA-methyltransferase (MGMT) is a repair protein, and its deficiency makes tumours more susceptible to the cytotoxic effect of alkylating agents. Five clinical trials with temozolomide or dacarbazine have been performed in metastatic colorectal cancer (mCRC) with selection based on methyl-specific PCR (MSP) testing with modest results. We hypothesised that mitigated results are consequences of unspecific patient selection and that alternative methodologies for MGMT testing such as immunohistochemistry (IHC) and digital polymerase chain reaction (PCR) could enhance patient enrolment...
January 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27989373/bleeding-after-invasive-procedures-is-rare-and-unpredicted-by-platelet-counts-in-cirrhotic-patients-with-thrombocytopenia
#9
Grazia Napolitano, Angelo Iacobellis, Antonio Merla, Grazia Niro, Maria Rosa Valvano, Fulvia Terracciano, Domenico Siena, Mariangela Caruso, Antonio Ippolito, Pier Mannucci Mannuccio, Angelo Andriulli
BACKGROUND: In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy. PATIENTS: In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations...
December 15, 2016: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/27974047/fgfr1-and-ntrk3-actionable-alterations-in-wild-type-gastrointestinal-stromal-tumors
#10
Eileen Shi, Juliann Chmielecki, Chih-Min Tang, Kai Wang, Michael C Heinrich, Guhyun Kang, Christopher L Corless, David Hong, Katherine E Fero, James D Murphy, Paul T Fanta, Siraj M Ali, Martina De Siena, Adam M Burgoyne, Sujana Movva, Lisa Madlensky, Gregory M Heestand, Jonathan C Trent, Razelle Kurzrock, Deborah Morosini, Jeffrey S Ross, Olivier Harismendy, Jason K Sicklick
BACKGROUND: About 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies. METHODS: We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations...
December 14, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27943127/prescription-of-anti-osteoporosis-medications-after-hospitalization-for-hip-fracture-a-multicentre-italian-survey
#11
Stefano Gonnelli, Carla Caffarelli, Giovanni Iolascon, Francesco Bertoldo, Giulia Letizia Mauro, Aurora Patti, Ranuccio Nuti
PURPOSE: Literature data indicate that the proportion of patients with recent hip fracture who receive a prescription for anti-osteoporotic drugs is low and does not seem to increase over time. This study aimed to obtain data on the prescription for anti-osteoporotic drugs in Italian patients discharged after a recent hip fracture and to assess which variables could have influenced the decision for prescribing osteoporosis medication. METHODS: A total of four Italian centres located in four different geographical areas (Siena, Verona, Naples and Palermo) participated in this retrospective study...
December 9, 2016: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#12
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27925185/effects-of-carbocysteine-and-beclomethasone-on-histone-acetylation-deacetylation-processes-in-cigarette-smoke-exposed-bronchial-epithelial-cells
#13
E Pace, S Di Vincenzo, M Ferraro, L Siena, G Chiappara, P Dino, P Vitulo, A Bertani, F Saibene, L Lanata, M Gjomarkaj
Histone deacetylase expression/activity may control inflammation, cell senescence, and responses to corticosteroids. Cigarette smoke exposure, increasing oxidative stress, may negatively affect deacetylase expression/activity. The effects of cigarette smoke extracts (CSE), carbocysteine, and beclomethasone dipropionate on chromatin remodelling processes in human bronchial epithelial cells are largely unknown. The present study was aimed to assess the effects of cigarette smoke, carbocysteine, and beclomethasone dipropionate on histone deacetylase 3 (HDAC3) expression/activity, N-CoR (nuclear receptor corepressor) expression, histone acetyltransferases (HAT) (p300/CBP) expression, p-CREB and IL-1 m-RNA expression, neutrophil chemotaxis...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925164/brain-volume-change-in-first-episode-psychosis-an-effect-of-antipsychotic-medication-independent-of-bmi-change
#14
K N Jørgensen, R Nesvåg, S Nerland, L Mørch-Johnsen, L T Westlye, E H Lange, U K Haukvik, C B Hartberg, I Melle, O A Andreassen, I Agartz
OBJECTIVE: The effect of antipsychotic medication on brain structure remains unclear. Given the prevalence of weight gain as a side-effect, body mass index (BMI) change could be a confounder. METHOD: Patients with first-episode psychosis (n = 78) and healthy controls (n = 119) underwent two 1.5T MRI scans with a 1-year follow-up interval. siena (fsl 5.0) was used to measure whole-brain volume change. Weight and height were measured at both time points. Antipsychotic medication use at baseline and follow-up was converted into chlorpromazine equivalent dose and averaged...
February 2017: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/27906440/supramicrosurgical-lymphatico-venular-anastomosis-lva-in-treating-lymphoedema-36-months-preliminary-report
#15
P Gennaro, G Gabriele, M Mihara, K Kikuchi, C Salini, I Aboh, F Cascino, G Chisci, C Ungari
OBJECTIVE: Lymphoedema of the extremities is a widespread pathological condition that mostly occurs as a complication of cancer resections, especially in women. Conventional therapy refers to conservative and physiotherapeutic approaches. Surgical strategies have been widely reported in the literature and are still challenging. Part of this literature focuses on the supra microsurgical lymphaticovenular anastomosis (LVA) technique. LVA is characterized by a high success rate, minimal invasivity and broad indications...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27883019/17-oxo-dha-displays-additive-anti-inflammatory-effects-with-fluticasone-propionate-and-inhibits-the-nlrp3-inflammasome
#16
Chiara Cipollina, Serena Di Vincenzo, Liboria Siena, Caterina Di Sano, Mark Gjomarkaj, Elisabetta Pace
Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function associated with increased local and systemic inflammatory markers, such as TNFα and IL-1β. Glucocorticoids are used to treat this chronic disease, however their efficacy is low and new drugs are very much required. 17-oxo-DHA is a cyclooxygenase-2-dependent, electrophilic, α,β-unsaturated keto-derivative of docosahexaenoic acid with anti-inflammatory properties. We evaluated the action of 17-oxo-DHA alone or in combination with the steroid fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy individuals exposed to lipopolysaccharide...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27870245/the-art-of-compiling-protein-binding-site-ensembles
#17
Stefan Bietz, Rainer Fährrolfes, Matthias Rarey
Structure-based drug design starts with the collection, preparation, and initial analysis of protein structures. With more than 115,000 structures publically available in the Protein Data Bank (PDB), fully automated processes reliably performing these important preprocessing steps are needed. Several tools are available for these tasks, however, most of them do not address the special needs of scientists interested in protein-ligand interactions. In this paper, we summarize our research activities towards an automated processing pipeline from raw PDB data towards ready-to-use protein binding site ensembles...
December 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27869986/physical-exercise-for-late-life-depression-customizing-an-intervention-for-primary-care
#18
Stamatula Zanetidou, Martino Belvederi Murri, Marco Menchetti, Giulio Toni, Fabrizio Asioli, Luigi Bagnoli, Donato Zocchi, Matteo Siena, Barbara Assirelli, Claudia Luciano, Mattia Masotti, Carlo Spezia, Monica Magagnoli, Mirco Neri, Mario Amore, Klea D Bertakis
OBJECTIVES: To identify which individual- and context-related factors influence the translation into clinical practice of interventions based on physical exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late-life major depression (LLMD). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary care with psychiatric consultation-liaison programs (PCLPs)-organizational protocols that regulate the clinical management of individuals with psychiatric disorders...
November 21, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27865140/overcoming-dynamic-molecular-heterogeneity-in-metastatic-colorectal-cancer-multikinase-inhibition-with-regorafenib-and-the-case-of-rechallenge-with-anti-egfr
#19
REVIEW
Andrea Sartore-Bianchi, Salvatore Siena, Giuseppe Tonini, Alberto Bardelli, Daniele Santini
In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade...
December 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27843629/clonal-evolution-and-kras-met-coamplification-during-secondary-resistance-to-egfr-targeted-therapy-in-metastatic-colorectal-cancer
#20
Andrea Sartore-Bianchi, Emanuele Valtorta, Alessio Amatu, Silvio Veronese, Calogero Lauricella, Erica Bonazzina, Giulia Siravegna, Mauro Truini, Alberto Bardelli, Salvatore Siena
No abstract text is available yet for this article.
2016: ESMO Open
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