tbuckley/cabot-search huggingface dataset:
OA06.06 Druggable Alterations Involving Crucial Carcinogenesis Pathways Drive the Prognosis of Squamous Cell Lung Carcinoma (SqCLC)
Authors: Sara Pilotto, Michele Simbolo, Isabella Sperduti, Silvia Novello, Caterina Vicentini, Umberto Peretti, Serena Pedron, Roberto Ferrara, Mario Caccese, Michele Milella, Andrea Mafficini, Paolo Visca, Marco Volante, Francesco Facciolo, Antonio Santo, Luisa Carbognin, Matteo Brunelli, Marco Chilosi, Aldo Scarpa, Giampaolo Tortora, Emilio Bria
Journal: Journal of Thoracic Oncology (2017)
Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10
Authors: Hamida Hammad, Matthias Vanderkerken, Philippe Pouliot, Kim Deswarte, Wendy Toussaint, Karl Vergote, Lana Vandersarren, Sophie Janssens, Ioanna Ramou, Savvas N Savvides, Jody J Haigh, Rudi Hendriks, Manfred Kopf, Katleen Craessaerts, Bart de Strooper, John F Kearney, Daniel H Conrad, Bart N Lambrecht
Journal: Nature Immunology (2017)
Clonal Evolution in Chronic Lymphocytic Leukemia: Acquisition of High-Risk Genomic Aberrations Associated with Unmutated VH, Resistance to Therapy, and Short Survival.
Authors: Stephan Stilgenbauer, Sandrine Sander, Lars Bullinger, Axel Benner, Elke Leupolt, Dirk Winkler, Alexander Kröber, Dirk Kienle, Peter Lichter, Hartmut Döhner
Journal: Blood (2006)
OA13.07 Intrapleural Modified Vaccine Strain Measles Virus Therapy for Patients with Malignant Pleural Mesothelioma
Authors: Tobias Peikert, Sumithra Mandrekar, Aaron Mansfield, Virginia Van Keulen, Steven Albelda, Sandra Aderca, Stephanie Carlson, Allen Dietz, Mike Gustafson, Robert Kratzke, Val Lowe, Fabien Maldonado, Julian Molina, Manish Patel, Anja Roden, Jin Sun, Angelina Tan, Maja Tippmann-Peikert, Evanthia Galanis
Journal: Journal of Thoracic Oncology (2017)
The -195C→G Substitution In Brazilian Hereditary Persistence of Fetal Hemoglobin Decreases NF-E1/YY1 Binding and Increases PAX1 Binding to the A Gamma Globin Promoter Region
Authors: Fernanda Marconi Roversi, Anderson Ferreira Cunha, Carolina Lanaro, Ana Flavia Brugnerotto, Maria Emília Favero, Dulcinéia Martins Albuquerque, Fernando Ferreira Costa
Journal: Blood (2010)
S41 Clinical relevance of pulmonary non-tuberculous mycobacteria isolated over 7 years at a single uk centre
Authors: HF Schiff, S Philpot, A Achaiah, A Pereira, G Stait, B Green
Journal: Thorax (2016)

<h3>Background</h3> The frequency of clinical isolation of non-tuberculous mycobacteria (NTM) from the respiratory tract is increasing. American Thoracic Society (ATS) criteria aid the identification of clinically relevant isolates causing lung disease. <h3>Objectives</h3> (1) to audit diagnostic criteria used when treating NTM at our hospital (2) to identify the most clinically relevant isolates in our region and (3) to identify relevant associated patient demographics and radiological features <h3>Methods</h3> records of all patients from whom NTM were isolated from respiratory samples between 2007 and 2014 were reviewed. Microbiological results, radiological findings and symptoms were reviewed to assess adherence to ATS diagnostic criteria and outcomes. <h3>Results</h3> NTM were isolated 826 times in 444 clinical episodes during the study period. Of 92 treated episodes, 81 (88%) met diagnostic criteria. If isolated, <i>M. abscessus</i> was most likely to be clinically relevant [Figure 1] and sputum smear positive. Isolation of <i>M. kansasii</i> and <i>M. malmoense</i> also warrant particular attention. Of the cases meeting ATS diagnostic criteria, the most common symptoms were fever, night sweats and weight loss. Concomitant oral steroid use and HIV positive status were common in this group. Cavitation and tree-in-bud were the most common CT radiographic appearances. <h3>Discussion</h3> 21% of all clinical episodes with NTM isolation were treated for NTM disease. 88% of cases met ATS diagnostic criteria suggesting good adherence to guidance. <h3>Reference</h3> Griffith DE, <i>et al</i>. An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. <i>Am J Respir Crit Care Med</i> 2007;<b>175</b>:367–416.
Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars
Authors: Antoine D'Hollander, Hilde Jans, Greetje Vande Velde, Charlotte Verstraete, Sam Massa, Nick Devoogdt, Tim Stakenborg, Serge Muyldermans, Liesbet Lagae, Uwe Himmelreich
Journal: Biomaterials (2017)
S128 Lungsearch: a randomised controlled trial of surveillance for the early detection of lung cancer in a high risk group
Authors: S Spiro, P Shah, R Rintoul, J George, S Janes, M Callister, M Novelli, P Shaw, C Griffths, M Falzon, G Kocjan, R Booton, N Magee, M Peake, P Dhillon, K Sridharan, J Allen, N Chinyanganya, V Ashford-Turner, N Counsell, A Hackshaw
Journal: Thorax (2016)

Screening for the early detection of lung cancers should increase the percentage of operable tumours, thus improving cure rates. A large randomised US trial showed that CT screening moderate/heavy smokers is effective but expensive, with a high false-positive rate. We designed LungSEARCH in 2006 to target screening in higher-risk subjects. Because most tumours in the UK were of squamous-histology, we hypothesised that sputum cytology plus cytometry would be an effective initial screen, only offering more intensive/expensive tests to those with abnormal sputum. Eligibility criteria were: current/former smokers (≥20 pack-years and/or smoked ≥20 years), GOLD-defined COPD, no prior cancer. Subjects were randomised to surveillance or a control group, and each followed for 5 years. Screened subjects provided sputum for central assessment, and those with abnormal results (cytology: low/high-grade squamous intraepithelial lesions, and/or cytometry: abnormal ploidy) were referred for annual low-dose CT and autofluorescence bronchoscopy (AFB) for the remainder of the trial, with diagnostic investigations when cancer suspected by abnormal CT/AFB. Sputum-negatives provided annual sputum samples only. Control subjects had a chest X-ray when they reached 5 years. Primary objective: to show a higher proportion of early stage cancers using surveillance than controls. 1568 subjects were recruited (target 1300) from GPs or chest clinics around 10 UK centres (August 2007–March 2011): 785 screened, 783 controls. Mean age 63 years; males 52%; current (56%), former (44%) smokers; mild (25%), moderate (75%) COPD; from GPs (79%). &gt;90% screened subjects provided sputum samples in their first year. After 5 years, the overall sputum-positive rate is 33%; 30% (236/785) had a CT scan and 25% (193/785) had an AFB at any time. Of those who had a CT scan 19% (45/236) were abnormal (lung nodule(s) ≥9 mm); and of those who had AFB 3% (5/193) had severe dysplasia or worse. 79 lung cancers have been identified to date via the centres/national registry: 43 surveillance and 36 control. But awaiting staging details for 6 surveillance and 14 control cases. Preliminary results are promising: 57% (surveillance) versus 41% (controls) of cancers were diagnosed with stage I/II non-small-cell-lung cancer or limited disease small-cell-lung cancer. Final data available later in 2016.
P3.03-013 BAP1 Immunostaining and FISH Analysis of p16 Help Making Distinction among Subtypes of Mesothelioma
Authors: Kenzo Hiroshima, Di Wu, Yasuo Sekine, Daisuke Ozaki, Toshikazu Yusa, Kouta Washimi, Reiji Haba, Yuji Tada, Hideaki Shimada, Masatoshi Tagawa
Journal: Journal of Thoracic Oncology (2017)
P1.02-071 Detection of Multiple Low-Frequency Mutations by Molecular-Barcode Sequencing
Authors: Kei Namba, Shuta Tomida, Hidejiro Torigoe, Hiroki Sato, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Journal: Journal of Thoracic Oncology (2017)
Abstract B19: Targeting dependencies within apoptotic pathways through inhibition of BET bromodomains
Authors: Andrew R. Conery, Richard C. Centore, Kerry L. Spillane, Nicole E. Follmer, Archana Bommi-Reddy, Charlie Hatton, Barbara M. Bryant, Patricia Greninger, Arnaud Amzallag, Cyril H. Benes, Jennifer A. Mertz, Robert J. Sims
Journal: Clinical Cancer Research (2017)

Abstract Cancer is driven in large part by dysregulated transcriptional programs that allow for the acquisition of the many ‘Hallmarks of Cancer.' Multiple regulatory factors are essential for the establishment and maintenance of these cancer-specific transcriptional programs, and this dependence creates vulnerabilities that can be therapeutically targeted. Here we describe a selective dependence on the bromodomain and extraterminal (BET) family of proteins for the reprogramming of apoptotic signaling networks and demonstrate how this dependence can be predicted prior to therapeutic intervention. We demonstrate in phenotypically sensitive cell lines that BET inhibition results in a rapid and robust transcriptional response among regulators of apoptosis, and that this transcriptional response is correlated with changes in the apoptotic threshold of target cells and subsequent apoptosis. We show that the robustness of the apoptotic response, and not that of the cytostatic response, predicts phenotypic sensitivity to BETi. Consistent with this, we observed that acquired BETi tolerance in two disparate cellular models is driven by dysregulated expression of anti-apoptotic BCL2 family proteins, and that genetic or pharmacological manipulation of apoptotic signaling can modify the phenotypic response to BETi. We further demonstrate that the basal expression levels of a set of apoptotic factors significantly predict preclinical response to BETi, and in particular note that BETi preferentially targets those cells that are dependent on BCL2 for survival. Our findings suggest that tumor cells have acquired a dependence on BET bromodomain function to evade apoptosis, and highlight opportunities to exploit this dependence in the clinic through rational patient selection and drug combination strategies. Citation Format: Andrew R. Conery, Richard C. Centore, Kerry L. Spillane, Nicole E. Follmer, Archana Bommi-Reddy, Charlie Hatton, Barbara M. Bryant, Patricia Greninger, Arnaud Amzallag, Cyril H. Benes, Jennifer A. Mertz, Robert J. Sims, III. Targeting dependencies within apoptotic pathways through inhibition of BET bromodomains. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B19.
Bone Marrow Immunophenotypic Analysis Allows the Identification of High Risk of Progression and Immune Condition-Related Monoclonal Gammopathy of Undetermined Significance.
Authors: AndrÉs Jerez, Francisco Ortuño, María del Mar Osma, Ignacio Español, Ana Gonzalez, Felipe de Arriba, Vanessa Roldán, Vicente Garcia
Journal: Blood (2009)
Hydralazine + Magnesium Valproate as Epigenetic Treatment for Myelodysplastic Syndrome (MDS). Preliminary Results of a Phase II Trial.
Authors: Myrna Candelaria, Aquileo Herrera, Juan Labardini, Aurora Gonzalez-Fierro, Catalina Trejo-Becerril, Erick de la Cruz-Hernandez, Brenda A la Torre-Talavera, Alfonso Duenas-Gonzalez
Journal: Blood (2009)
Private firms run a third of CCGs’ schemes to screen GP referrals
Authors: Gareth Iacobucci
Journal: BMJ (2017)

At least 24 clinical commissioning groups across England are paying private companies to screen referrals from GPs to specialist care, The BMJ has found.

The BMJ ’s investigation found that two fifths of CCGs that responded to its requests for information use a referral management system of some kind,1 despite previous evidence casting doubt on the effectiveness of such systems.2

The analysis—the first to track the number of referral management schemes in operation since CCGs were established in 2013—comes afte r The BMJ recently reported details of North Durham CCG’s decision to …
S74 Increased respiratory syncytial virus burden leads to more rapid cell death in PHE508DEL bronchial epithelial cells
Authors: MS Coates, EWFW Alton, DW Brookes, K Ito, JC Davies
Journal: Thorax (2016)

<h3>Introduction</h3> Respiratory syncytial virus (RSV) leads to serious lower respiratory tract disease and prolonged periods of symptoms in cystic fibrosis (CF) patients. This study aims to determine whether RSV viral burden and the level of cytopathic effect (CPE) is higher in CF bronchial epithelial cells. <h3>Methods</h3> Paired immortalised bronchial epithelial cell lines, CFBE41o-, expressing either wild type (WT) or Phe508del CFTR were infected with RSV A2 at an MOI of 0, 0.01, 0.1 and 1.0. Cell viability was measured daily by Resazurin assay, and viral burden by plaque assay in HEp-2 cells and RT-PCR. Viral attachment was determined by PCR after incubating RSV with the cells for 2 hrs at 4°C. Intracellular RSV proteins were measured by western blot. <h3>Results</h3> Phe508del CFTR cells showed significantly greater and more rapid CPE by RSV (0.1 and 1 MOI) compared to WT cells. Viral burden was increased in the Phe508del cells each day up to 7 days post infection. The levels of intracellular RSV genetic material determined by PCR were also increased by 4.0 ± 0.2 (mean of MOIs ± SD) fold at 12 hours post infection in CF cells compared to WT. It was confirmed that increased levels of viral RNA led to increased intracellular viral proteins. Virus shedding determined by PCR in the supernatant at 24 hours post infection was also increased by 10.7 ± 5.0 fold in CF cells. There was no evidence of increased RSV attachment to CF cells. <h3>Conclusion</h3> RSV causes CPE in bronchial epithelial cells expressing Phe508del CFTR more rapidly than in WT cells. This increased CPE was associated with an increased viral burden, which occurs despite similar levels of cell attachment and is therefore likely due to increased viral replication or transcription within the cell, which led to increased levels of intracellular RSV proteins. The mechanism for this is under investigation.
Apolipoprotein E (APOE) Genotype as a Determinant of Survival in Women with Chronic Lymphocytic Leukemia.
Authors: J. Brice Weinberg, Alicia D. Volkheimer, Mirta Mihovilovic, Ning Jiang, Youwei Chen, Joseph O. Moore, Jon P. Gockerman, Louis F. Diehl, Carlos M. de Castro, David A. Rizzieri, Marc C. Levesque, Robert DeKroon, Warren J. Strittmatter
Journal: Blood (2007)
TGF-β Receptor I Kinase Inhibitor Downregulates Cytokine Secretion and Multiple Myeloma Cell Growth in the Bone Marrow Microenvironment.
Authors: Toshiaki Hayashi, Teru Hideshima, Klaus Podar, Paul Richardson, Olivier Munoz, Makoto Hamasaki, Kenji Ishitsuka, Hiroshi Yasui, Alison Murphy, Glenn McEnroe, Sarvajit Chakravarty, Sundeep Dugar, Linda S. Higgins, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2004)
PUB041 HGF, VEGFA and ANGPT2 Predict Clinical Benefit from Bevacizumab and Chemotherapy in Patients with Advanced NSCLC (SAKK19/09)
Authors: Sacha Rothschild, Oliver Gautschi, Nathalie Schuster, Qiyu Li, Spasenija Savic, Martina Schneider, Christine Biaggi, Lukas Bubendorf, Martin Brutsche, Alfred Zippelius, Thilo Zander, Daniel Betticher, Martin Früh, Rolf Stahel, Richard Cathomas, Daniel Rauch, Miklos Pless, Adrian Ochsenbein, Rolf Jaggi
Journal: Journal of Thoracic Oncology (2017)
P2.01-055 Lymphocytes' Subtypes Differentiation after Stimulation with Synthetic Antigen-Pulsed Dendritic Cells in Lung Adenocarcinoma Patients
Authors: Kamila Wojas-Krawczyk, Tomasz Kucharczyk, Pawel Krawczyk, Iwona Homa-Mlak, Janusz Milanowski
Journal: Journal of Thoracic Oncology (2017)
OA07.01 Incidence, Local Distribution and Impact of pN2 Skip Metastasis in Patients Undergoing Curative Resection for NSCLC
Authors: Ariane Steindl, Sabrina Tahon, Mai Nguyen, Balazs Dome, Viktoria Laszlo, Walter Klepetko, Mir Hoda, Thomas Klikovits
Journal: Journal of Thoracic Oncology (2017)
PMP22 genetic alteration and modulation of PMP22 expression by NSC-631570 in pancreatic ductal adenocarcinoma (PDAC).
Authors: N. Funel, S. Pelliccioni, A. C. Insilla, M. Denaro, E. Giovannetti, L. Pollina, A. Michelucci, P. Simi, F. Mosca, U. Boggi, D. Campani
Journal: Journal of Clinical Oncology (2011)

e14589 Background: Peripheral myelin protein 22 gene (PMP22) encodes a membrane protein in peripheral nervous system, and PMP22 duplication causes the Charcot Marie Tooth (CMT1A) phenotype. PMP22 is also capable of delaying G0/G1 to S phase transition (growth arrest specific gene 3, GAS3). However, growth factors involved in PMP22 regulation, such as Insulin-like growth factor II (IGF-II), are up-regulated after radiation in fibroblasts, and might influence chemo-radiosensitivity. Since NSC-631570 had a protective effect on fibroblasts but not tumour cells against ionizing radiation, and showed beneficial effects in phase II studies in metastatic and locally advanced PDAC, the aim of this study was to evaluate the interaction between PMP22, IGF-II and NSC-631570 in PDAC Primary Cell Cultures (PCCs). Methods: DNA duplication of PMP22 gene was evaluated by PCR and digestion by EcoRI and NsiI endonucleases in 13 PDAC tissues, 2 PCCs and PBMCs from 3 healthy subjects (used as negative controls in genetic tests for CMT1A syndrome). PMP22 protein expression was evaluated in tissues and cells by ImmunoHistoChemistry, using a quantitative scoring (eg, 0 absent, 1 low, 2 intermediate and 3 high expression). The PCCs were also exposed to IGF-II, NSC-631570, and their combination. Finally, expression of PMP22 was correlated with cell proliferation index. Results: PMP22 duplication was observed in 44% of PDACs and both PCCs. PDAC amplified samples showed significantly higher score of PMP22 protein expression (p=0.026). PMP22 protein expression was correlated with decreased cell growth, whereas 400 nM IGF-II reduced PMP22 expression and increased cell proliferation. Conversely, the addition of 1mM NSC-631570 increased PMP22 expression and overcame IGF-II induced proliferation. Conclusions: This is the first study reporting PMP22 duplication in PDAC tissues and cells. This duplication was correlated with PMP22 expression. PMP22 expression was inversely related to cell proliferation and its inhibition by IGF-II might explain chemo-radioresistance caused by PDAC associated fibroblasts. However, NSC-631570 increased PMP22 expression and might synergize with anticancer treatments against PDAC.
Prioritization of Generic Drug Review
Authors: Maryll Toufanian, John R. Peters, Kathleen Uhl
Journal: JAMA Internal Medicine (2017)

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Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study
Authors: Olivier Lortholary, Marie Olivia Chandesris, Cristina Bulai Livideanu, Carle Paul, Gérard Guillet, Ewa Jassem, Marek Niedoszytko, Stéphane Barete, Srdan Verstovsek, Clive Grattan, Gandhi Damaj, Danielle Canioni, Sylvie Fraitag, Ludovic Lhermitte, Sophie Georgin Lavialle, Laurent Frenzel, Lawrence B Afrin, Katia Hanssens, Julie Agopian, Raphael Gaillard, Jean-Pierre Kinet, Christian Auclair, Colin Mansfield, Alain Moussy, Patrice Dubreuil, Olivier Hermine
Journal: The Lancet (2017)
P61 Community oxygen prescriptions and DNACPR discussions in stockport; an opportunity to improve end of life care planning?
Authors: C Morris, S Parry, P Holmes, V Gupta
Journal: Thorax (2016)

<h3>Introduction</h3> Many patients who are prescribed home oxygen are symptomatic from progressive, life-limiting disease. The GMC recommends “if cardiac or respiratory arrest is an expected part of the dying process and CPR will not be successful, making and recording an advance decision not to attempt CPR will help to ensure that the patient dies in a dignified and peaceful manner”.<sup>1</sup> In addition, patients who are at risk of death or declining are identified on the gold standard framework (GSF) and future care planned according to their wishes.<sup>2</sup> <h3>Objectives</h3> To investigate whether patients prescribed oxygen in the community had Do Not Attempt CPR (DNACPR) discussed and recorded; and secondly to investigate the length of time these patients were on oxygen and had DNACPR discussed/recorded prior to death. <h3>Methods</h3> Patients who died between January and June 2016 on home oxygen were identified from the Stockport Home Oxygen Service records. The Stockport Health Record (SHR) and GP practices were consulted to find patients’ primary diagnoses and DNACPR status. <h3>Results</h3> 43 patients (mean age 73.8 ± 1.8) were identified. The overall median (range) length of time on home oxygen was 191 (5–3617) days. 14 (32.6%) had a community DNACPR form present or discussed 60.7 ± 24.4 days (mean ± sem) prior to death. Most common diagnoses were COPD (n = 19), malignancy (n = 14), ILD (n = 5) and other eg CF, PE (n = 3). Results for these groups are shown in Table 1. <h3>Conclusion</h3> Patients are prescribed home oxygen for many reasons and for variable amounts of time. For many the prescription represents a deterioration in their health. In our cohort of patients only 32.6% had DNACPR discussed/present at death, and median survival after initiation of oxygen was only 191 days. <h3>References</h3> End of life care: When to consider making a Do Not Attempt CPR (DNACPR) decision. http://www.gmc-uk.org/guidance/ethical_guidance/end_of_life_DNACPR_ decision.asp. Gold Standards Framework. http://www.goldstandardsframework.org.uk/.
HIV Infection and Heart Failure Outcomes in Women
Authors: Sumbal A. Janjua, Virginia A. Triant, Daniel Addison, Balint Szilveszter, Susan Regan, Pedro V. Staziaki, Steven A. Grinspoon, Udo Hoffmann, Markella V. Zanni, Tomas G. Neilan
Journal: Journal of the American College of Cardiology (2017)