tbuckley/cabot-search huggingface dataset:
S6 MMP12 and LMO7, two key players on opposite sides of early lung squamous cell carcinoma development
Authors: A Barrett, S Lourenco, K Kolluri, B Carroll, M Falzon, E Borg, J George, SM Janes, VH Teixeira
Journal: Thorax (2016)

<h3>Background</h3> Our laboratory has a unique cohort of patients with pre-invasive lung squamous cell carcinoma (SqCC) lesions, within which there is a clear discrepancy between the prevalence of pre-invasive lesions and the incidence of lung cancer, suggesting that not all pre-invasive lesions progress to cancer. Using gene expression microarrays we identified 1846 genes significantly differentially expressed between progressive and regressive pre-invasive SqCC lesions. The macrophage metalloelastase MMP12 gene was found to be highly expressed in progressive lesions, and we hypothesised that it plays a role in epithelial-to-mesenchymal transition (EMT). Conversely, the actin binding protein LIM-domain only 7 (LMO7) gene was highly expressed in regressive lesions, and we postulated that it may be protective against EMT due to its role in the maintenance of epithelial architecture. Initial studies using three SqCC cell lines (A431, H357 and H376) with MMP12-shRNA knockdown showed a significant decrease in migration and invasion compared to non-silencing shRNA controls. LMO7-shRNA knockdown in HBECS was found to significantly increase migration. The aim of this study is to further characterise the function and signalling of MMP12 and LMO7 in lung SqCC development. <h3>Methods</h3> Eight-week-old NOD/SCID mice were used for tumorigenesis experiments. Adhesion assays were carried out to assess the roles of MMP12-knockdown or LMO7-overexpression on cell adhesion. Cell signalling mechanisms were assessed using western blotting, qPCR and immunostaining. <h3>Results</h3> We observed that MMP12-knockdown decreases tumorigenicity in an immunocompromised mouse model. Both A431- and H357 MMP12-knockdown cells produced significantly smaller tumours compared with non-silencing shRNA cells. We found that MMP12-knockdown decreases cell adhesion, which is currently being further investigated along with effects on integrin signalling pathways. Levels of EMT markers were assessed in MMP12-knockdown and LMO7 overexpressing cells using qPCR, western blotting and immunostaining. Results indicate that higher MMP12 expression is associated with a mesenchymal phenotype, whereas higher LMO7 expression is associated with an epithelial phenotype. <h3>Conclusions</h3> Our results suggest that MMP12 is a key driver of migration and invasion in SqCC and its high expression may contribute to EMT, whereas LMO7 is a putative tumour suppressor with a crucial role in maintaining epithelial cell architecture. MMP12 and LMO7 may be potential early stage therapeutic markers for lung cancer.
P3.03-046 Prognostic Fibrinogen/Leucocyte Score at Diagnosis Predicts Survival and Benefit from Multimodality Treatment in MPM
Authors: Thomas Klikovits, Pietro Bertoglio, Marcello Ambrogi, Paul Stockhammer, Yawen Dong, Balazs Dome, Viktoria Laszlo, Walter Klepetko, Alfredo Mussi, Mir Hoda
Journal: Journal of Thoracic Oncology (2017)
An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration
Authors: Lei Zhao, Guojun Chen, Jun Li, Yingmei Fu, Timur A. Mavlyutov, Annie Yao, Robert W. Nickells, Shaoqin Gong, Lian-Wang Guo
Journal: Journal of Controlled Release (2017)
Disulfiram, An Old Drug with New Potential Therapeutic Uses for Human Haematological Malignancies
Authors: Concetta Conticello, Daniela Martinetti, Laura Lombardo, Simona Buccheri, Luana Adamo, Gabriella Amato, Maide Cavalli, Annalisa Chiarenza, Ruggero de Maria, Rosario Giustolisi, Massimo Gulisano, Francesco Di Raimondo
Journal: Blood (2008)
Abstract 13840: Stress Myocardial Perfusion Imaging Compared to Coronary Computed Tomography in Patients With Suspected Coronary Artery Disease: an International Randomized Controlled Trial
Authors: Ganesan Karthikeyan, Barbara G Salobir, Borut Jug, Erick Alexanderson, Niveditha Devasenapathy, Joao Vitola, Otakar Kraft, Elgin Ozkan, Diana Paez, Ravi Kashyap
Journal: Circulation (2015)

Introduction: Functional imaging by stress myocardial perfusion imaging (MPI) and anatomical imaging by coronary computed tomographic angiography (CTA) are interchangeably used in the initial evaluation of patients with suspected coronary artery disease (CAD). Patients undergoing stress MPI as the initial study may require downstream testing less often when compared to those undergoing CTA. Methods: In this international, multicenter, open-label, randomized controlled trial, mildly symptomatic patients who had an intermediate likelihood of having CAD, and asymptomatic patients who were at intermediate risk of cardiac events, were randomized to undergo either initial stress MPI or coronary CTA. Randomization was stratified by site and symptom status. The primary outcome was downstream noninvasive or invasive testing at 6 months. The primary analysis was by intention-to-treat, after adjustment for site, symptom status and physician preference for MPI or CTA. The planned sample size was 500. Because of slow recruitment, the study was stopped at the end of 3 years, without knowledge of outcome data. (NCT01368770) Results: Between June 2011 and 2014, we recruited 303 patients (151 MPI and 152 CTA) from 6 centres in 6 countries. Average patient age was 59 years, 28% were diabetic, 80% had chest pain as the presenting symptom, and over 95% underwent the allocated study procedures. The initial test was abnormal in 29% (41/143) of patients in the MPI arm and in 56% (79/141) of the CTA arm.Fewer patients undergoing initial stress MPI had the primary outcome (adjusted OR 0.53, 95% CI 0.29 - 0.94, p=0.03). There were no important differences in the average cost per patient, or the median effective radiation dose between the strategies at 12 months. (Table) Conclusions: In the management of patients with intermediate likelihood of CAD, a strategy of initial stress MPI is substantially less likely to require further downstream testing than initial coronary CTA.
Differential Clearance Kinetics and Phenotypic Alterations of Leukaemic Blast Cells during Induction Therapy for Hyperdiploid and t(12;21) Childhood ALL: Implications for Minimal Residual Disease Detection by Flow Cytometry and Clinical Outcome.
Authors: Matthew J. Cullen, Anita J. Dickinson, Helen Dickinson, Michael A. Short, Paul A.S. Evans, Sally E. Kinsey, Mike Richards, Stephen J. Richards
Journal: Blood (2004)
P1.06-038 Survival and Prognostic Factors of Oligometastatic Non-Small Cell Lung Carcinoma: A Single Center Experience
Authors: Derya Kızılgöz, Pınar Akın Kabalak, Ugur Yılmaz, Tuba Inal Cengiz, Metehan Karaca, Evrim Tunç, Selim Şakir Erkmen Gülhan, Kyle Wang
Journal: Journal of Thoracic Oncology (2017)
MA06.11 Phase II Study of Nimotuzumab + Concurrent Chemoradiotherapy (CRT) for Stage III Non-Small Cell Lung Cancer (NSCLC): 5-Year Follow-Up Results
Authors: Kazushige Hayakawa, Yasumasa Nishimura, Hideyuki Harada, Toshinori Soejima, Kayoko Tsujino, Takuyo Kozuka, Masahiro Tanaka, Tomonari Sasaki, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Journal: Journal of Thoracic Oncology (2017)
In Vitro Anti-Myeloma Activity of the Multitargeted Kinase Inhibitor Midostaurin in the Context of Heterotypic Cocultures of Myeloma Cells with Nonmalignant Microenvironmental Accessory Cells
Authors: Panisinee Lawasut, Hannah M. Jacobs, Jake E Delmore, Joseph Negri, Douglas W. McMillin, Ellen L Weisberg, James D. Griffin, Paul G. Richardson, Kenneth C Anderson, Constantine S. Mitsiades
Journal: Blood (2011)
Firearm Acquisition Without Background Checks
Authors: Matthew Miller, Lisa Hepburn, Deborah Azrael
Journal: Annals of Internal Medicine (2017)

In 1994, 40% of U.S. gun owners who had recently acquired a firearm did so without a background check. No contemporary estimates exist.To estimate the proportion of current U.S. gun owners who acquired their most recent firearm without a background check, by time since and manner of acquisition, for the nation as a whole and separately in states with and without legislation regulating private sales.Probability-based online survey.United States, 2015.1613 adult gun owners.Current gun owners were asked where and when they acquired their last firearm; if they purchased the firearm; and whether, as part of that acquisition, they had a background check (or were asked to show a firearm license or permit).22% (95% CI, 16% to 27%) of gun owners who reported obtaining their most recent firearm within the previous 2 years reported doing so without a background check. For firearms purchased privately within the previous 2 years (that is, other than from a store or pawnshop, including sales between individuals in person, online, or at gun shows), 50% (CI, 35% to 65%) were obtained without a background check. This percentage was 26% (CI, 5% to 47%) for owners residing in states regulating private firearm sales and 57% (CI, 40% to 75%) for those living in states without regulations on private firearm sales.Potential inaccuracies due to recall and social desirability bias.22% of current U.S. gun owners who acquired a firearm within the past 2 years did so without a background check. Although this represents a smaller proportion of gun owners obtaining firearms without background checks than in the past, millions of U.S. adults continue to acquire guns without background checks, especially in states that do not regulate private firearm sales.Fund for a Safer Future and the Joyce Foundation.
S35 Efficacy and safety of the direct switch from various previous treatments to glycopyrronium or indacaterol/glycopyrronium in patients with moderate copd: the crystal study
Authors: C Vogelmeier, M Aalamian-Mattheis, T Greulich, J M Marin, W Castellani, T Similowski, V Ninane, M Gaga, S Lane, X Nunez, F Patalano, A Clemens, K Kostikas
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> In contrast to clinical trials, changes to new therapies in clinical practice occur without any washout period. The CRYSTAL study was designed to mimic clinical practice. Patients with symptomatic, non-frequently exacerbating, moderate COPD treated with various drugs were directly switched to glycopyrronium 50 μg (GLY) or indacaterol/glycopyrronium 110/50 μg (IND/GLY). Lung function and symptoms were evaluated. <h3>Methods</h3> CRYSTAL was a prospective, multicentre, 12-week, randomised, pragmatic, open-label trial. Patients were recruited into 4 Groups according to previous medication and symptoms (mMRC) and randomised to a direct switch to GLY or IND/GLY vs. continuation of baseline therapy (3:1). Co-primary objectives were superiority of GLY vs. previous SABA and/or SAMA, non-inferiority of GLY vs. previous LABA or LAMA, and superiority of IND/GLY vs. LABA, LAMA and LABA+ICS regarding trough FEV1 and transition dyspnoea index (TDI) at Week 12. Due to slow recruitment, Groups A and B were prematurely discontinued at the time of completion of Groups C and D. <h3>Results</h3> Of the 4,389 patients randomised, 2,159 patients received IND/GLY (C2: n = 811; D2: n = 811) or continued their previous treatment (LABA + ICS C1: n = 269; LABA or LAMA D1: n = 268). IND/GLY provided superior improvement in trough FEV1 at Week 12 vs. LABA + ICS (treatment difference (Δ) = 71 mL, p &lt; 0.0001) and LABA or LAMA (Δ = 101 mL, p &lt; 0.0001). IND/GLY also improved TDI vs. LABA + ICS (Δ = 1.10 units, p &lt; 0.0001) and vs. LABA or LAMA (Δ = 1.26 units, p &lt; 0.0001). Significantly more patients on IND/GLY reached the minimally clinically important difference (MCID) of 100 mL for trough FEV1 and 1 point for TDI vs. comparators (<b>Table 1</b>). In the Groups A and B that were underpowered due to sample size, GLY was superior to previous SABA and/or SAMA and was non-inferior to previous LABA or LAMA on trough FEV1 and TDI (<b>Table 1</b>). GLY and IND/GLY were well tolerated. <h3>Conclusions</h3> In the pragmatic CRYSTAL trial, IND/GLY demonstrated superior improvement in lung function (trough FEV1) and dyspnoea (TDI) after 12 weeks, in symptomatic patients with moderate COPD and a history of up to 1 exacerbation in the previous year, after direct switch from previous treatment with either LABA+ICS or with a LABA or LAMA.
Pre-Stem Cell Transplant Induction Therapy Does Not Affect Post-Transplant Survival In Light Chain (AL) Amyloidosis
Authors: Sumit Madan, Shaji Kumar, Martha Lacy, Angela Dispenzieri, Francis Buadi, Suzanne R. Hayman, David Dingli, S. Vincent Rajkumar, Morie Gertz
Journal: Blood (2010)
Identification of Mcl-1 as a Novel Target in Neoplastic Mast Cells and Demonstration of Cooperative Growth-Inhibitory Effects of mcl-1 Antisense Oligonucleotides, PKC412, and AMN107.
Authors: Karl J. Aichberger, Matthias Mayerhofer, Karoline V. Gleixner, Maria-Theresa Krauth, Sophia Derdak, Winfried F. Pickl, Volker Wacheck, Edgar Selzer, Hermine Agis, Christian Sillaber, Peter Valent
Journal: Blood (2005)
Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction
Authors: Iris E. Allijn, Bertrand M.S. Czarny, Xiaoyuan Wang, Suet Yen Chong, Marek Weiler, Acarilia Eduardo da Silva, Josbert M. Metselaar, Carolyn Su Ping Lam, Giorgia Pastorin, Dominique P.V. de Kleijn, Gert Storm, Jiong-Wei Wang, Raymond M. Schiffelers
Journal: Journal of Controlled Release (2017)
P1.07-015 STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC
Authors: Penella Woll, Piers Gaunt, Nicola Steele, Samreen Ahmed, Clive Mulatero, Riyaz Shah, Sarah Danson, Elizabeth Hodgkinson, Karen James, Ben Watkins, Peter Fletcher, Lucinda Billingham
Journal: Journal of Thoracic Oncology (2017)
MA04.01 Non-Amplification Mutation of ERBB2 in EGFR-Mutated Lung Cancer
Authors: Kyle Gowen, Balazs Halmos, Robert Hoyer, Woondong Jeong, James Suh, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, Siraj Ali, Alexa Schrock, James Sun, Vincent Miller, Philip Stephens, Jeffrey Ross, Laurie Gay
Journal: Journal of Thoracic Oncology (2017)
Procalcitonin-Guided Antimicrobial Therapy—All About the Algorithm—Reply
Authors: Konrad Reinhart, Frank Bloos
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Inhibition of Tumor Growth by RGD Peptide Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature.
Authors: Torsten Kessler, Ralf Bieker, Teresa Padro, Federico Herrera, Sandra Ruiz, Hubert Serve, Micheal Kreuter, Wolfgang E. Berdel, Rolf M. Mesters
Journal: Blood (2004)
P295 Efficacy and safety of tiotropium/olodaterol in patients with copd by ats category
Authors: F Maltais, E Pizzichini, L Grönke, F Voß, E Derom
Journal: Thorax (2016)

<h3>Rationale</h3> The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β<sub>2</sub>-agonist, has demonstrated efficacy and safety in chronic obstructive pulmonary disease (COPD).<sup>1</sup> Recently, it has been demonstrated that patients with milder disease (GOLD 2) have better bronchodilator responses compared to those with more severe disease. This <i>post hoc</i> analysis investigated whether the response to T/O and to T alone is influenced by forced expiratory volume in 1 second (FEV<sub>1</sub>) American Thoracic Society (ATS) category (mild, moderate or severe). <h3>Methods</h3> In total, 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (via Respimat<sup>®</sup> inhaler) in two 52-week, parallel-group, double-blind studies (TONADO<sup>®</sup> 1 and 2: NCT01431274; NCT01431287). This <i>post hoc</i> analysis focuses on the T 5 µg and T/O 5/5 µg analyses. Primary efficacy end points were trough FEV<sub>1</sub> response (ie, change from baseline) and FEV<sub>1</sub> area under the curve from 0–3 hours (AUC<sub>0–3</sub>) response. Data are presented for patients by ATS category subgroups: mild (predicted FEV<sub>1</sub> ≥50%), moderate (35 ≤ 50%) and severe (&lt;35%), using data pooled from both of the TONADO<sup>®</sup> studies. <h3>Results</h3> In all disease-severity categories, the improvements in trough FEV<sub>1</sub> and FEV<sub>1</sub> AUC<sub>0–3</sub> were larger with T/O compared to T alone. However, trough FEV<sub>1</sub> and FEV<sub>1</sub> AUC<sub>0–3</sub> responses were generally greater in patients with mild (T/O versus T: both p &lt; 0.0001) or moderate (T/O versus T: p &lt; 0.001 and p &lt; 0.0001, respectively) COPD versus those with severe COPD (T/O versus T: p &lt; 0.01 and p &lt; 0.0001, respectively) at baseline (Table). Treatments were well tolerated across all ATS categories and similar responses were observed in both of the studies individually. <h3>Conclusions</h3> These data build on the analysis of the GOLD 2 population from TONADO<sup>®</sup> and confirm that patients with mild to moderate disease derive greater benefits with T/O than with T. There was an overall trend towards greater lung-function improvement with T/O or T alone in patients with mild/moderate versus severe airflow obstruction. <h3>Funding</h3> Boehringer Ingelheim. <h3>Reference</h3> Buhl R, <i>et al</i>. <i>Eur Respir J</i> 2015;<b>45</b>:969–979. Please refer to page A273 for declarations of interest in relation to abstract P295.
Gastric bypass achieves sustained weight loss in severely obese teenagers, studies show
Authors: Susan Mayor
Journal: BMJ (2017)

Gastric bypass surgery achieves dramatic weight loss in severely obese teenagers and helps them maintain a lower body weight for more than five years of follow-up but with high rates of nutritional deficiencies, show two studies providing long term data on the impact of obesity surgery in this age group.1 2

Around 30% of adolescents in the US and 22-25% in Europe are overweight or obese, and one in 20 children and adolescents in the US (6.3%) is severely obese—defined as having a body mass index (BMI) of 40 or over (around 100 lb (45 kg) overweight). Lifestyle modification and medical treatment have little effect in this …
The F-Box Protein NIPA Regulates the Hematopoietic Stem Cell Pool
Authors: Stefanie Kreutmair, Anna Lena Illert, Rouzanna Istvanffy, Melanie Sickinger, Christina Eckl, Corinna Albers, Christian Peschel, Robert A.J. Oostendorp, Justus Duyster
Journal: Blood (2011)
Comment on “On the Utility of ToxCast™ and ToxPi as Methods for Identifying New Obesogens”
Authors: Keith A. Houck, Richard S. Judson, Thomas B. Knudsen, Matthew T. Martin, Ann M. Richard, Kevin M. Crofton, Anton Simeonov, Richard S. Paules, John R. Bucher, Russell S. Thomas
Journal: Environmental Health Perspectives (2017)
Association of Remnant Liver Ischemia With Early Recurrence and Poor Survival After Liver Resection in Patients With Hepatocellular Carcinoma
Authors: Jai Young Cho, Ho-Seong Han, YoungRok Choi, Yoo-Seok Yoon, Sungho Kim, Jang Kyu Choi, Jae Seong Jang, Seong Uk Kwon, Haeryoung Kim
Journal: JAMA Surgery (2017)

The remnant liver after hepatectomy may have inadequate blood supply, especially following nonanatomical resection or vascular damage.To evaluate whether remnant liver ischemia (RLI) may have an adverse effect on long-term survival and morbidity after liver resection in patients with hepatocellular carcinoma.This study was a retrospective analysis at Seoul National University Bundang Hospital. Remnant liver ischemia was graded on postoperative computed tomographic scans in 328 patients who underwent hepatectomy for hepatocellular carcinoma between January 1, 2004, and December 31, 2013.Remnant liver ischemia was defined as reduced or absent contrast enhancement during the venous phase. Remnant liver ischemia was classified as minimal (none or marginal) or severe (partial, segmental, or necrotic).Among 328 patients (252 male and 76 female; age range, 26-83 years [mean age, 58.2 years]), radiologic signs of severe RLI were found in 98 patients (29.9%), of whom 63, 16, and 19 had partial, segmental, or necrotic RLI, respectively. These patients experienced more complications and longer hospital stay than patients with minimal RLI. Preoperative history of transarterial embolization (odds ratio [OR], 1.77; 95% CI, 1.02-3.03; P = .04), use of the Pringle maneuver (OR, 1.96; 95% CI, 1.08-3.58; P = .03), and longer operative time (OR, 1.003; 95% CI, 1.002-1.005; P < .001) were independent risk factors for severe RLI. Early recurrence rates within 6 (60.2% vs 9.6%) or 12 (79.6% vs 18.7%) months after hepatectomy were higher in patients with severe RLI than in patients without RLI (P < .001). Severe remnant liver ischemia was an independent risk factor for overall survival (OR, 6.98; 95% CI, 4.27-11.43; P < .001) and disease-free survival (OR, 5.15; 95% CI, 3.62-7.35; P < .001).Preventive management and technical refinements in hepatectomy are important to decrease the risk of RLI and to improve survival of patients with hepatocellular carcinoma.