tbuckley/cabot-search huggingface dataset:
P269 Acquisition of epidemic pseudomonas aeruginosa strains in non-cf bronchiectasis patients
Authors: C Keil, S Manzoor, S Gossain, K Hardy, JL Whitehouse
Journal: Thorax (2016)

<h3>Background</h3> <i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that chronically colonises the lungs of bronchiectasis patients and is associated with a decline in lung function. Epidemic strains of <i>P. Aeruginosa</i> including Liverpool, Manchester and Midlands-1, have been described in cystic fibrosis (CF) patients and have been associated with increased morbidity and mortality, but have not previously been described in broncheiectasis patients. This study aimed to establish if there was cross transmission of <i>P. aeruginosa </i>amongst bronciectaisis patients and if epidemic strains were present. <h3>Material/methods</h3> During the period February 2013 to May 2014 <i>P. aeruginosa</i> isolates from sputum samples from bronchiectasis patients were collected. The samples were taken in both primary and secondary care. All isolates were epidemiologically typed using multiple-locus variable number tandem repeat (VNTR) typing. For 20 patients multiple isolates from the same sample were analysed and for 14 patients multiple samples were analysed. A strain-specific PCR to identify the Midlands-1 and Liverpool epidemic <i>P. aeruginosa</i> strains was used on a sub-set of isolates that had VNTR profiles related to known Liverpool and Midland-1 epidemic strains. <h3>Results</h3> VNTR profiles were obtained for a total of 144 isolates from 84 patients. A total of 126 unique VNTR profiles were observed. Typing of multiple isolates from the same sample and the same patient revealed multiple types, with STRD &gt; 3 in 10/20 isolates from the same sample and 14/15 of multiple samples from the same patient. A total of 3 patients were chronically infected with epidemic strains, one with Midlands-1 and two with Liverpool. All of these patients had had long stays on the cystic fibrosis ward where patients with the epidemic strains are nursed. <h3>Conclusions</h3> Cross transmission of the <i>P. aeruginosa</i> epidemic strains from the CF population to the bronchiectasis patients occurred on several occasions. However, there is no evidence of cross transmission of non-epidemic strains amongst the bronchiectasis population. This study provides evidence for segregating bronchiectasis and cystic fibrosis patients to prevent acquisition of epidemic strains. Prospective data is required to see if patients develop <i>Pseudomonas aeruginosa</i> infection if seen in non-segregated clinic spaces.
Expression (Exp) of FIP200 and Rb in breast cancer (BreastCA) metastasis (met) to the brain and effect on survival.
Authors: M. Burgett, N. Hashemi Sadraei, M. S. Ahluwalia, R. Tipps, D. Khosla, A. S. Nowacki, R. Weil, R. Prayson, C. Gladson
Journal: Journal of Clinical Oncology (2011)

e21152 Background: BreastCA is the most common non-cutaneous cancer and the 2nd leading cause of cancer deaths. Although the outcome for BreastCA patients (pts) with brain met remains poor, there is significant variation in overall survival (OS). However, there are no markers or to predict OS. FIP200 is a signaling node regulating several pathways. It inhibits cell proliferation when localized to the nucleus by promoting Rb-1 and p21, and it promotes cell survival when localized to the cytoplasm through inhibition of Pyk2 and regulation of autophagy. FIP200 gene is deleted or mutated in approximately 20 % of primary BreastCA biopsies, and the level of Exp of FIP200 and Rb1 are correlated in BreastCA cell lines. The Exp of FIP200 and its cellular localization have not been examined in brain met of any cancer. Methods: In a single institution retrospective analysis brain tissues on 21 pts with metastatic BreastCA, obtained between 8/2000 and 3/2010 were evaluated for Exp of FIP200 and Rb1. These biopsies were selected based on the availability of adequate tissue in the blocks and a prior diagnosis (Dx) of invasive ductal BreastCA. Immunohistochemistry was used to evaluate the localization and levels of Exp of FIP200 and Rb1 which in turn were tested as predictors of prolonged OS. Results: 37% of primary breastCA were triple negative, 25% were ER negative/HER2 positive. Median time from Dx to met in the 21 pts was 23 (0-245) months (mos), and the median OS from Dx of BreastCA was 43 (6-264) mos. Nuclear Exp of Rb1 was detected in < 30% vs. ≥ 30% of cells in 11 vs. 10 pts. The median OS was 39 (range 6-264) mos in pts with Rb1 Exp < 30% of cells and 47 (20-190) mo in those with Rb1 Exp in ≥ 30% of cells. Nuclear Exp of FIP200 was detected in <20% vs. ≥ 20% of cells in 13 vs. 8 pts. The median OS was 39 (6-264) mos in pts with FIP200 nuclear Exp in <20% of cells and 45 (43-122) mos in those with FIP200 Exp in ≥ 20% of cells. Cytoplasmic Exp of Fip200 was detected in ≥ 20% of cells in 20 of 21 cases. Conclusions: The pattern of nuclear Exp of Rb1 is different in pts with brain met from invasive intra-ductal BreastCA with a longer OS. An expanded study is underway to determine whether nuclear Rb1 and/or FIP200 predict OS and define the role of these proteins in brain met from BreastCA.
P2.06-029 Pilot Window-Of-Opportunity Study of Pembrolizumab in Patients with Resectable Malignant Pleural Mesothelioma (MPM)
Authors: Hedy Kindler, Mark Ferguson, Yi-Huang Tan, Buerkley Rose, Mehwish Ahmad, Samuel Armato, Christopher Straus, Theodore Karrison, Tanguy Seiwert
Journal: Journal of Thoracic Oncology (2017)
P3.05-006 Anxiolytic Effect of Acupuncture in a Phase II Study of Acupuncture and Morphine for Dyspnea in Lung Cancer and Mesothelioma
Authors: Anna Minchom, Ravi Punwani, Jacqueline Filshie, Jaishree Bhosle, Kofi Nimako, James Myerson, Ranga Gunapala, Sanjay Popat, Mary O'Brien
Journal: Journal of Thoracic Oncology (2017)
Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2
Authors: Yuchun Niu, Feng Ma, Weimei Huang, Shun Fang, Man Li, Ting Wei, Linlang Guo
Journal: Molecular Cancer (2017)

Abstract Background Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism. Methods The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer. Results We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC. Conclusions Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.
P1.01-038 Prognosis Value of Body Mass Index (BMI) and Weight Loss at Diagnosis in Primary Lung Cancer: Results of KBP-2010-CPHG Study
Authors: Didier Debieuvre, Hugues Morel, Bruno Raynard, Jean-Philippe Oster, Acya Bizieux, Antoine Lévy, Jean-Pierre Mathieu, Patrick Dumont, Étienne Leroy-Terquem, Bernard Asselain, François Blanchon, Michel Grivaux
Journal: Journal of Thoracic Oncology (2017)
TLR-2 Signal Pathway Is Enhanced in Myeloproliferative Neoplasm - Related to the Increased Infammatory Cytokine and Pathogenesis?
Authors: Guanfang Shi, Maryna Yarotska, Hui Chen, Abdelmalek Cherif, Ching Wong, Madhumati Kalavar, Vladimir Gottlib, Jen-Chin Wang
Journal: Blood (2015)
P2.03a-054 A Single-Arm Phase II Study of Nab-Paclitaxel for Patients with Chemorefractory Non-Small Cell Lung Cancer
Authors: Hisashi Tanaka, Kageaki Taima, Takeshi Morimoto, Yoshihito Tanaka, Masamichi Itoga, Kunihiko Nakamura, Akihito Hayashi, Mika Kumagai, Hideo Yasugahira, Megumi Mikuniya, Koichi Okudera, Shingo Takanashi, Sadatomo Tasaka
Journal: Journal of Thoracic Oncology (2017)
P3.03-043 Trimodality Therapy with Extrapleural Pneumonectomy, Radiation Therapy, and Chemotherapy for Epithelioid Malignant Pleural Mesothelioma
Authors: Kazunori Okabe, Hiroyuki Tao, Masataro Hayashi, Masashi Furukawa, Daigo Murakami, Hideharu Hironaka, Akio Hara
Journal: Journal of Thoracic Oncology (2017)
P274 Cognitive function in idiopathic pulmonary fibrosis
Authors: C Sharp, HI Adamali, AB Millar, JW Dodd
Journal: Thorax (2016)

<h3>Introduction</h3> Patients with Chronic Obstructive Pulmonary Disease (COPD) are known to have cognitive dysfunction and share many co-morbidities with those with Idiopathic Pulmonary Fibrosis (IPF). This led us to hypothesise that patients with IPF may also have cognitive dysfunction. To investigate this, we conducted a prospective, observational study examining cognitive function in IPF patients with normal oxygen saturations, comparing them to COPD and smoking controls. <h3>Methods</h3> Patients with IPF and oxygen saturations &gt;88% in room air were recruited from outpatient clinics. Exclusion criteria were dementia, neurological disease and illiteracy. Data from the NOVASC study were used for the COPD and control arms. Pulmonary physiology results and demographic data, including educational and smoking status were collected. Patients completed the Montreal Cognitive Assessment (MoCA) and Hospital Anxiety and Depression Scale (HADS). Group differences were assessed using unpaired t-test, analysis of variance and χ2 test. Multivariable linear regression models were constructed to establish which variables contributed to observed variability in MoCA results. <h3>Results</h3> 30 patients with IPF were recruited and were compared to 31 patients with COPD and 26 smoking controls. Results are shown in Table 1. MoCA scores were lower in both IPF and COPD groups and a greater proportion of IPF patients had scores in the "mild cognitive dysfunction" range of 18–25 (46.7%, compared to COPD 32.3%, control 11.5%, p = 0.018). We also compared the IPF cohort to normative data in a population aged 70–79. The mean MoCA in this population was 27.5 (SD = 5.56, n = 53). The IPF patients had a significantly lower MoCA score (p = 0.035). A multivariable linear regression model including diagnosis, age, education and FVC predicted 18.8% of the variance in MoCA (F (4,79) = 4.57, p = 0.002). Age was the only significant variable. <h3>Conclusions</h3> 46.7% of non-hypoxaemic patients with ILD demonstrate at least mild cognitive dysfunction, some of this can be explained by the effect of age, but compared to published age adjusted normative data, there remains a significant reduction in cognitive function in IPF. This cognitive dysfunction has implications for decision making around treatments in IPF which may have significant side-effects.
Mother Donors Confer Protection Against Infectious Mortality after Haploidentical T Cell-Depleted Hematopoietic Transplantation
Authors: Loredana Ruggeri, Antonella Tosti, Antonella Mancusi, Fabiana Topini, Elena Urbani, Alessandra Carotti, Massimo Fabrizio Martelli, Andrea Velardi
Journal: Blood (2014)
Abstract B04: Synthetic lethal targeting of E-cadherin-deficient cancers
Authors: Parry J. Guilford, Augustine Chen, Bryony Telford, Andrew Single, Henry Beetham, Tanis Godwin
Journal: Clinical Cancer Research (2017)

Abstract Germline mutation of the E-cadherin gene (CDH1) genetically defines the inherited cancer syndrome hereditary diffuse gastric cancer (HDGC). HDGC is characterized by highly penetrant diffuse gastric cancer (DGC) and an elevated rate of lobular breast cancer (LBC). Somatic CDH1 mutations also occur frequently in the sporadic forms of these cancers. We propose that the loss of E-cadherin, a tumor suppressor gene, creates vulnerabilities in the cancer cell that can be exploited with drugs (“synthetic lethal” interactions). We are particularly interested in identifying drugs that can be used for the chemoprevention of advanced disease in HDGC family members by targeting the multifocal precursor lesions that occur in stomach and breast tissue. In the stomach, these early lesions are mucosally-confined stage T1a signet ring cell carcinomas. Up to 400 independent foci have been identified in the stomachs of CDH1 mutation carriers; these foci are genetically homogenous and are likely to only require the 2nd CDH1 hit for their initiation. To identify the vulnerabilities created by E-cadherin loss, we have conducted a genome-wide siRNA knockdown screen, a 4000 compound known drug screen and a 114,000 compound library screen in isogenic MCF10a breast cell lines with and without E-cadherin expression. The functional screen has shown that GPCR signaling proteins are highly enriched amongst the candidate synthetic lethal proteins, as well as many protein classes associated cell signaling and cytoskeletal function. Drugs that show increased activity against the E-cadherin-deficient cells include the JAK inhibitor LY2784544, the c-SRC inhibitor saracatanib, the beta-2 adrenoreceptor (GPCR) agonist formoterol, several HDAC inhibitors and statins. Detail on synergistic combinations involving many of these drugs is provided in the abstract entitled “Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors”. To identify mechanisms associated with E-cadherin synthetic lethality, we used the cell viability data from the siRNA screen to examine the distributions of cell viabilities for the genes that make up the major KEGG signaling pathways. Using the Kolomogorov-Smirnof method to test for significance, we identified the PI3K-AKT survival pathway as being central to E-cadherin's synthetic lethal associations. These findings pave the way for the development of rationally designed drug combinations for the chemoprevention and treatment of E-cadherin-negative cancers. Citation Format: Parry J. Guilford, Augustine Chen, Bryony Telford, Andrew Single, Henry Beetham, Tanis Godwin. Synthetic lethal targeting of E-cadherin-deficient cancers. [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 B04.
JCES01.18 Dual Positive PD-L1 and CD8+ TIL Represents a Predominant Subtype in NSCLC and Correlates with Augmented Immunogenicity
Authors: Si-Yang Liu, Zhong-Yi Dong, Wen-Zhao Zhong, Si-Pei Wu, Zhi Xie, Hai-Yan Tu, Yi Long Wu
Journal: Journal of Thoracic Oncology (2017)
P1.07-030 Gene Signature of EMT in Neuroendocrine Lung Carcinoma: A Comparative Analysis with Adenocarcinoma and Squamous Cell Carcinoma
Authors: Tabatha Prieto, Vanessa De Sá, Eloisa Olivieri, Eduardo Da Silva, Rui Reis, Dirce Carraro, Vera Capelozzi
Journal: Journal of Thoracic Oncology (2017)
P3.02a-034 Vemurafenib in Patients with Non-Small Cell Lung Cancer (NSCLC) Harboring BRAF Mutation. Preliminary Results of the AcSé Trial
Authors: Julien Mazieres, Claire Cropet, Fabrice Barlesi, Pierre Jean Souquet, Virginie Avrillon, Bruno Coudert, Jacques Le Treut, Frederique Orsini Piocelle, Gilles Quere, Elizabeth Fabre, Jean Tredaniel, Marie Wislez, Olivier Huillard, Eric Dansin, Denis Moro-Sibilot, Helene Blons, Gilbert Ferretti, Etienne Lonchamp, Natalie Hoog Labouret, Veronica Pezzella, Céline Mahier Ait Oukhatar, Jean-Yves Blay
Journal: Journal of Thoracic Oncology (2017)
P3.07-020 Implementation of an International Value-Based Standard Set of Outcomes for Lung Cancer Patients in a Brazilian Center
Authors: Clarissa Baldotto, Luiz H. Araujo, Mauro Zukin, Mayara Baptista, Perla De Mello Andrade, Natalia Carvalho, Nelson Teich
Journal: Journal of Thoracic Oncology (2017)
P1.03-046 Selection of Subjects at High-Risk for LDCT Lung Cancer Screening Using a Molecular Panel: Results by the ITALUNG Biomarker Study
Authors: Francesca Carozzi, Laura Carrozzi, Fabio Falaschi, Andrea Lopes Pegna, Mario Mascalchi, Giulia Picozzi, Francesco Pistelli, Ferruccio Aquilini, Cristina Ocello, Luana Greco, Cristina Sani, Marco Peluso, Simonetta Bisanzi, Eugenio Paci
Journal: Journal of Thoracic Oncology (2017)
Nonpharmacologic treatment of common atrial flutter guided by transient entrainment.
Authors: Toshinori Fujimoto, Shigeki Itoh, Katsuhisa Takaoka, Hiroyuki Kurogane, Yutaka Yoshida, Tsuyosh Kawamura, Kyoichi Ogawa, Tomoo Inoue, Mitsuhiro Yokoyama
Journal: Circulation (1993)

We attempted nonpharmacologic treatment for common atrial flutter in 7 patients, with direct current catheter ablation (CA) in 5 cases and cryoablation in 2 cases under the guidance of transient entrainment. Transient entrainment during common atrial flutter by pacing from the mid or low lateral right atrium (LLRA) revealed a long conduction time between the LLRA and the orifice of the coronary sinus (CSo) (73% to 121% of flutter cycle length). In 2 cases, fragmented electrograms were recorded at the low right atrial septum with durations of 150 msec and 155 msec, respectively. Because these fragmented electrograms were transiently entrained by rapid atrial pacing in the same manner as other atrial electrograms and were recorded in an area of long conduction, we believe that fragmented electrograms represent critical slow conduction. In 5 cases, CA was directed at this area. Three cases were successfully treated with 3 to 4 DC shocks of 100 J (follow up periods of 11.3, 4.5 and 3 months). Two cases which received I to 2 DC shocks of 100 J had recurrence of atrial flutter 6 and 4.7 months later, respectively. Two cases which showed atrial septal defect received surgical treatment. They were successfully treated with extended cryoablation in this same area (follow up periods of 26 and 9.2 months). In conclusion, extended ablation of an area of fragmented electrograms using transient entrainment may be an effective treatment for common atrial flutter.
Treatment of Primary and Secondary Hemochromatosis and Acute Iron Poisoning with a New, Potent Iron-Eliminating Agent (Desferrioxamine-B)
Authors: Sven Moeschlin, Urs Schnider
Journal: New England Journal of Medicine (1963)

THE purpose of this paper is to study the clinical value of a new, potent, specific iron-eliminating agent (desferrioxamine-B, or DFOM)§ in cases of chronic iron overload (primary and secondary hemochromatosis) and to evaluate experimentally its clinical value in acute iron poisoning.Until recently, the excessive amounts of stored iron in primary hemochromatosis could be eliminated only by venesection. Secondary hemochromatosis in sideroachrestic anemia, aplastic anemia (transfusions), thalassemia major and sickle-cell anemia remained a still unsolved problem. Different chelating agents were tried but proved unsatisfactory because of toxic side reactions or elimination of other essential oligometals, such as copper and . . .
P1.05-055 Risk Factors of Postoperative Recurrence in Stage IA and IB Patients
Authors: Fumihiko Hoshi, Akira Sakurada, Toru Hasumi, Tetsu Sado, Masafumi Noda, Yasushi Matsuda, Shunsuke Eba, Hideki Mitomo, Takeo Togo, Masato Katahira, Yoshinori Okada
Journal: Journal of Thoracic Oncology (2017)
Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis
Authors: Audrey S L Low, Deborah P M Symmons, Mark Lunt, Louise K Mercer, Chris P Gale, Kath D Watson, William G Dixon, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs). Methods This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression. Results 252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups. Conclusions Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control.
Methylation Status of Tumor Suppressor Genes BEX2, IGSF4, RARB and TIMP3 Is Indicative for AML with Translocations of the MLL Gene.
Authors: Hilmar Quentmeier, Willy G. Dirks, Stefan Nagel, Sonja Röhrs, Björn Schneider, Hans G. Drexler
Journal: Blood (2007)