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https://www.readbyqxmd.com/read/28431480/predictive-and-prognostic-factors-associated-with-soft-tissue-sarcoma-response-to-chemotherapy-a-subgroup-analysis-of-the-european-organisation-for-research-and-treatment-of-cancer-62012-study
#1
Robin J Young, Saskia Litière, Michela Lia, Pancras C W Hogendoorn, Cyril Fisher, Gunhild Mechtersheimer, Søren Daugaard, Raf Sciot, Françoise Collin, Christina Messiou, Viktor Grünwald, Alessandro Gronchi, Winette van der Graaf, Eva Wardelmann, Ian Judson
BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy...
April 21, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28376997/ebola-2014-setting-up-a-port-health-screening-programme-at-an-international-train-station
#2
Vivien Cleary, Edward Wynne-Evans, James Freed, Katie Fleet, Simone Thorn, Deborah Turbitt
An outbreak of Ebola virus disease (EVD) began in Guinea in December 2013 and was declared a Public Health Emergency of International Concern by the World Health Organization in August 2014. In October, the UK government tasked Public Health England (PHE) to set up EVD screening at key ports. The key aim of port-of-entry screening was to identify passengers coming from areas with high risk of EVD, and give them advice to raise their awareness of symptoms and what actions to take. Direct flights from Sierra Leone, Guinea or Liberia had all been cancelled, so intelligence on passenger numbers and routes was used to identify the most commonly used routes from the affected countries into the UK...
December 1, 2017: Journal of Business Continuity & Emergency Planning
https://www.readbyqxmd.com/read/28362562/ten-year-progression-free-and-overall-survival-in-patients-with-unresectable-or-metastatic-gi-stromal-tumors-long-term-analysis-of-the-european-organisation-for-research-and-treatment-of-cancer-italian-sarcoma-group-and-australasian-gastrointestinal-trials
#3
Paolo G Casali, John Zalcberg, Axel Le Cesne, Peter Reichardt, Jean-Yves Blay, Lars H Lindner, Ian R Judson, Patrick Schöffski, Serge Leyvraz, Antoine Italiano, Viktor Grünwald, Antonio Lopez Pousa, Dusan Kotasek, Stefan Sleijfer, Jan M Kerst, Piotr Rutkowski, Elena Fumagalli, Pancras Hogendoorn, Saskia Litière, Sandrine Marreaud, Winette van der Graaf, Alessandro Gronchi, Jaap Verweij
Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued...
March 31, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28147291/source-apportionment-of-ambient-fine-and-coarse-particulate-matter-at-the-fort-mckay-community-site-in-the-athabasca-oil-sands-region-alberta-canada
#4
Matthew S Landis, J Patrick Pancras, Joseph R Graney, Emily M White, Eric S Edgerton, Allan Legge, Kevin E Percy
An ambient air particulate matter sampling study was conducted at the Wood Buffalo Environmental Association (WBEA) AMS-1 Fort McKay monitoring station in the Athabasca Oil Sand Region (AOSR) in Alberta, Canada from February 2010 to July 2011. Daily 24h integrated fine (PM2.5) and coarse (PM10-2.5) particulate matter was collected using a sequential dichotomous sampler. Over the duration of the study, 392 valid daily dichotomous PM2.5 and PM10-2.5 sample pairs were collected with concentrations of 6.8±12.9μgm(-3) (mean±standard deviation) and 6...
April 15, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28122596/high-prevalence-of-autoimmune-disease-in-the-rare-inflammatory-bone-disorder-sternocostoclavicular-hyperostosis-survey-of-a-dutch-cohort
#5
Pieter A Valkema, Clare H Luymes, Janneke E Witteveen, Saskia le Cessie, Natasha M Appelman-Dijkstra, Pancras C W Hogendoorn, Neveen A T Hamdy
BACKGROUND: Sternocostoclavicular hyperostosis (SCCH; ORPHA178311) is a rare inflammatory disorder of the axial skeleton, the precise pathophysiology of which remains to be established. We addressed the potential association of SCCH with autoimmune processes by evaluating the lifetime prevalence of autoimmune disease in 70 patients with adult-onset SCCH and 518 SCCH-unaffected first-degree relatives (parents, siblings and children). Danish hospital registry data for autoimmune diseases were used as reference data...
January 25, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28109409/ecco-essential-requirements-for-quality-cancer-care-soft-tissue-sarcoma-in-adults-and-bone-sarcoma-a-critical-review
#6
REVIEW
Elisabeth Andritsch, Marc Beishon, Stefan Bielack, Sylvie Bonvalot, Paolo Casali, Mirjam Crul, Roberto Delgado- Bolton, Davide Maria Donati, Hassan Douis, Rick Haas, Pancras Hogendoorn, Olga Kozhaeva, Verna Lavender, Jozsef Lovey, Anastassia Negrouk, Philippe Pereira, Pierre Roca, Godelieve Rochette de Lempdes, Tiina Saarto, Bert van Berck, Gilles Vassal, Markus Wartenberg, Wendy Yared, Alberto Costa, Peter Naredi
BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28105277/design-and-synthesis-of-novel-meta-linked-phenylglycine-macrocyclic-fviia-inhibitors
#7
Jeremy M Richter, Daniel L Cheney, J Alex Bates, Anzhi Wei, Joseph M Luettgen, Alan R Rendina, Timothy M Harper, Rangaraj Narayanan, Pancras C Wong, Dietmar Seiffert, Ruth R Wexler, E Scott Priestley
Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28053157/blockade-of-protease-activated-receptor-4-par4-provides-robust-antithrombotic-activity-with-low-bleeding
#8
Pancras C Wong, Dietmar Seiffert, J Eileen Bird, Carol A Watson, Jeffrey S Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M Miller, R Michael Lawrence, Jacques Banville, Julia Guy, Brad D Maxwell, E Scott Priestley, Anne Marinier, Ruth R Wexler, Michel Bouvier, David A Gordon, William A Schumacher, Jing Yang
Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/27994741/discovery-of-phenylglycine-lactams-as-potent-neutral-factor-viia-inhibitors
#9
Nicholas R Wurtz, Brandon L Parkhurst, Wen Jiang, Indawati DeLucca, Xiaojun Zhang, Vladimir Ladziata, Daniel L Cheney, Jeffrey R Bozarth, Alan R Rendina, Anzhi Wei, Joseph M Luettgen, Yiming Wu, Pancras C Wong, Dietmar A Seiffert, Ruth R Wexler, E Scott Priestley
Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27612545/synthesis-and-p1-sar-exploration-of-potent-macrocyclic-tissue-factor-factor-viia-inhibitors
#10
Vladimir Uladzimir Ladziata, Peter W Glunz, Yan Zou, Xiaojun Zhang, Wen Jiang, Swanee Jacutin-Porte, Daniel L Cheney, Anzhi Wei, Joseph M Luettgen, Timothy M Harper, Pancras C Wong, Dietmar Seiffert, Ruth R Wexler, E Scott Priestley
Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27573709/loss-of-h3k27-tri-methylation-is-a-diagnostic-marker-for-malignant-peripheral-nerve-sheath-tumors-and-an-indicator-for-an-inferior-survival
#11
Arjen Hg Cleven, Ghadah A Al Sannaa, Inge Briaire-de Bruijn, Davis R Ingram, Matt van de Rijn, Brian P Rubin, Maurits W de Vries, Kelsey L Watson, Kelia E Torres, Wei-Lien Wang, Sjoerd G van Duinen, Pancras Cw Hogendoorn, Alexander J Lazar, Judith Vmg Bovée
No abstract text is available yet for this article.
September 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27569442/comparison-of-mapie-versus-map-in-patients-with-a-poor-response-to-preoperative-chemotherapy-for-newly-diagnosed-high-grade-osteosarcoma-euramos-1-an-open-label-international-randomised-controlled-trial
#12
Neyssa M Marina, Sigbjørn Smeland, Stefan S Bielack, Mark Bernstein, Gordana Jovic, Mark D Krailo, Jane M Hook, Carola Arndt, Henk van den Berg, Bernadette Brennan, Bénédicte Brichard, Ken L B Brown, Trude Butterfass-Bahloul, Gabriele Calaminus, Heike E Daldrup-Link, Mikael Eriksson, Mark C Gebhardt, Hans Gelderblom, Joachim Gerss, Robert Goldsby, Allen Goorin, Richard Gorlick, Holcombe E Grier, Juliet P Hale, Kirsten Sundby Hall, Jendrik Hardes, Douglas S Hawkins, Knut Helmke, Pancras C W Hogendoorn, Michael S Isakoff, Katherine A Janeway, Heribert Jürgens, Leo Kager, Thomas Kühne, Ching C Lau, Patrick J Leavey, Stephen L Lessnick, Leo Mascarenhas, Paul A Meyers, Hubert Mottl, Michaela Nathrath, Zsuzsanna Papai, R Lor Randall, Peter Reichardt, Marleen Renard, Akmal Ahmed Safwat, Cindy L Schwartz, Michael C G Stevens, Sandra J Strauss, Lisa Teot, Mathias Werner, Matthew R Sydes, Jeremy S Whelan
BACKGROUND: We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. METHODS: EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation...
October 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27455395/discovery-of-a-highly-potent-selective-and-orally-bioavailable-macrocyclic-inhibitor-of-blood-coagulation-factor-viia-tissue-factor-complex
#13
Xiaojun Zhang, Peter W Glunz, James A Johnson, Wen Jiang, Swanee Jacutin-Porte, Vladimir Ladziata, Yan Zou, Monique S Phillips, Nicholas R Wurtz, Brandon Parkhurst, Alan R Rendina, Timothy M Harper, Daniel L Cheney, Joseph M Luettgen, Pancras C Wong, Dietmar Seiffert, Ruth R Wexler, E Scott Priestley
Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show excellent efficacy and minimal bleeding in preclinical models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimization of the P' groups led to a series of highly potent and selective TF-FVIIa inhibitors which displayed poor permeability. Fluorination of the aminoisoquinoline reduced the basicity of the P1 group and significantly improved permeability. The resulting lead compound was highly potent, selective, and achieved good pharmacokinetics in dogs with oral dosing...
August 11, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27369431/expression-of-ccl21-in-ewing-sarcoma-shows-an-inverse-correlation-with-metastases-and-is-a-candidate-target-for-immunotherapy
#14
Laurens G L Sand, Dagmar Berghuis, Karoly Szuhai, Pancras C W Hogendoorn
Ewing sarcoma is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. For patients with metastatic disease in particular, immunotherapy has been proposed as possible beneficial additive therapy. CCL21 activation-based immunotherapy was successful in preclinical studies in other tumor types; therefore, we investigated CCL21 expression in Ewing sarcoma as potential target for immunotherapy. The CCL21 RNA expression was determined in 21 Ewing sarcoma cell lines and 18 primary therapy-naive Ewing sarcoma samples...
August 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27235790/branch-number-matters-promoting-catalytic-reduction-of-4-nitrophenol-over-gold-nanostars-by-raising-the-number-of-branches-and-coating-with-mesoporous-sio2
#15
Pancras Ndokoye, Qidong Zhao, Xinyong Li, Tingting Li, Moses O Tade, Shaobin Wang
In this study, we demonstrate for the first time that highly branched gold nanostars (AuNSs) and silica-coated AuNSs (AuNSs@mSiO2) could potentially serve as efficient hydrogenation catalysts. The catalytic activity could be promoted by raising the number of tipped-branches of AuNSs, which reveals that the tips play an important role as active sites. The fabricated sharply-pointed AuNSs benefit the electron transfer from BH4 anions to 4-nitrophenol. Coating AuNSs with mesoporous silica (AuNSs@mSiO2) further enhanced the reduction rate and recyclability, and also contributed to reducing the induction period...
September 1, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27165360/automation-of-technology-for-cancer-research
#16
REVIEW
Wietske van der Ent, Wouter J Veneman, Arwin Groenewoud, Lanpeng Chen, Claudia Tulotta, Pancras C W Hogendoorn, Herman P Spaink, B Ewa Snaar-Jagalska
Zebrafish embryos can be obtained for research purposes in large numbers at low cost and embryos develop externally in limited space, making them highly suitable for high-throughput cancer studies and drug screens. Non-invasive live imaging of various processes within the larvae is possible due to their transparency during development, and a multitude of available fluorescent transgenic reporter lines.To perform high-throughput studies, handling large amounts of embryos and larvae is required. With such high number of individuals, even minute tasks may become time-consuming and arduous...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27067390/prevalence-of-anaemia-and-associated-risk-factors-among-pregnant-women-attending-antenatal-care-in-gulu-and-hoima-regional-hospitals-in-uganda-a-cross-sectional-study
#17
Gerald Obai, Pancras Odongo, Ronald Wanyama
BACKGROUND: Anaemia is a public health problem affecting over 1.62 billion people globally. It affects all age groups of people and is particularly more prevalent in pregnant women. Africa carries a high burden of anaemia; in Uganda 24 % of women of child bearing age have anaemia. Pregnant women living in poverty are at greater risk of developing iron deficiency anaemia. The objective of this study was to determine the prevalence of anaemia and the associated risk factors in pregnant women attending antenatal care at Gulu and Hoima Regional Hospitals in Northern and Western Uganda respectively...
April 11, 2016: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/27015008/atropisomer-control-in-macrocyclic-factor-viia-inhibitors
#18
Peter W Glunz, Luciano Mueller, Daniel L Cheney, Vladimir Ladziata, Yan Zou, Nicholas R Wurtz, Anzhi Wei, Pancras C Wong, Ruth R Wexler, E Scott Priestley
Incorporation of a methyl group onto a macrocyclic FVIIa inhibitor improves potency 10-fold but is accompanied by atropisomerism due to restricted bond rotation in the macrocyclic structure, as demonstrated by NMR studies. We designed a conformational constraint favoring the desired atropisomer in which this methyl group interacts with the S2 pocket of FVIIa. A macrocyclic inhibitor incorporating this constraint was prepared and demonstrated by NMR to reside predominantly in the desired conformation. This modification improved potency 180-fold relative to the unsubstituted, racemic macrocycle and improved selectivity...
April 28, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26990975/loss-of-h3k27-tri-methylation-is-a-diagnostic-marker-for-malignant-peripheral-nerve-sheath-tumors-and-an-indicator-for-an-inferior-survival
#19
Arjen H G Cleven, Ghadah A Al Sannaa, Inge Briaire-de Bruijn, Davis R Ingram, Matt van de Rijn, Brian P Rubin, Maurits W de Vries, Kelsey L Watson, Kelia E Torres, Wei-Lien Wang, Sjoerd G van Duinen, Pancras C W Hogendoorn, Alexander J Lazar, Judith V M G Bovée
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases...
June 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/26956700/nikolay-ivanovich-pirogov-1810-1881-a-pioneering-russian-surgeon-and-medical-scientist
#20
Inge F Hendriks, James G Bovill, Peter A van Luijt, Pancras Cw Hogendoorn
Nikolay Pirogov qualified as a physician from Moscow University in 1828 and then studied surgery and anatomy at University of Dorpat. He developed new surgical techniques, including the eponymous osteoplastic foot amputation. His application of scientifically based techniques extended surgery from a craft to a science. During the Crimean War he initiated the deployment of women as nurses and used triage for dealing with mass casualties. His textbook on field surgery became the standard reference on the subject and his principles remained virtually unchanged until the Second World War...
March 8, 2016: Journal of Medical Biography
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