tbuckley/cabot-search huggingface dataset:
Glucose transporter 4 promotes head and neck squamous cell carcinoma metastasis through the TRIM24-DDX58 axis
Authors: Yu-Chan Chang, Li-Hsing Chi, Wei-Ming Chang, Chia-Yi Su, Yuang-Feng Lin, Chi-Long Chen, Ming-Huang Chen, Peter Mu-Hsin Chang, Alex T. H. Wu, Michael Hsiao
Journal: Journal of Hematology & Oncology (2017)

Head and neck squamous cell carcinoma (HNSCC) represents a unique and major health concern worldwide. Significant increases in glucose uptake and aerobic glycolysis have been observed in HNSCC cells. Glucose transporters (GLUTs) represent a major hub in the glycolysis pathway, with GLUT4 having the highest glucose affinity. However, GLUT4's role in HNSCC has not been fully appreciated. An in silico analysis was performed in HNSCC cohorts to identify the most significant glucose transporter associated with HNSCC patient prognosis. An immunohistochemical analysis of a tissue microarray with samples from 90 HNSCC patients was used to determine the association of GLUT4 with prognosis. Complementary functional expression and knockdown studies of GLUT4 were performed to investigate whether GLUT4 plays a role in HNSCC cell migration and invasion in vitro and in vivo. The detailed molecular mechanism of the function of GLUT4 in inducing HNSCC cell metastasis was determined. Our clinicopathologic analysis showed that increased GLUT4 expression in oral squamous cell carcinoma patients was significantly associated with a poor overall survival (OS, P = 0.035) and recurrence-free survival (RFS, P = 0.001). Furthermore, the ectopic overexpression of GLUT4 in cell lines with low endogenous GLUT4 expression resulted in a significant increase in migratory ability both in vitro and in vivo, whereas the reverse phenotype was observed in GLUT4-silenced cells. Utilizing a GLUT4 overexpression model, we performed gene expression microarray and Ingenuity Pathway Analysis (IPA) to determine that the transcription factor tripartite motif-containing 24 (TRIM24) was the main downstream regulator of GLUT4. In addition, DDX58 was confirmed to be the downstream target of TRIM24, whose downregulation is essential for the migratory phenotype induced by GLUT4–TRIM24 activation in HNSCC cells. Here, we identified altered glucose metabolism in the progression of HNSCC and showed that it could be partially attributed to the novel link between GLUT4 and TRIM24. This novel signaling axis may be used for the prognosis and therapeutic treatment of HNSCC in the future.
Under half of new cancer drugs increase survival by three months, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

New cancer drugs vary greatly in improving overall survival and the quality of life they achieve when compared with previous treatments, says a study systematically evaluating health technology assessments of new anticancer agents approved from 2003 to 2013.1

“There are growing questions about the value gained from spending on what seem to be ever more expensive cancer medicines,” said the researchers, led by Elias Mossialos, of the London School of Economics and Political Science in London, UK.

The use of many different outcome measures …
OA20.01 Tumor Mutation Burden (TMB) is Associated with Improved Efficacy of Atezolizumab in 1L and 2L+ NSCLC Patients
Authors: Marcin Kowanetz, Wei Zou, David Shames, Craig Cummings, Naiyer Rizvi, Alexander Spira, Garrett Frampton, Vincent Leveque, Susan Flynn, Simonetta Mocci, Geetha Shankar, Roel Funke, Marcus Ballinger, Daniel Waterkamp, Daniel Chen, Alan Sandler, Garret Hampton, Lukas Amler, Priti Hegde, Matthew Hellmann
Journal: Journal of Thoracic Oncology (2017)
OA20.06 Prospective ImmunogenomiC PrOfiling of Non-Small Cell Lung Cancer - The ICON Project
Authors: Boris Sepesi, Icon Team, John Heymach, Padmanee Sharma, James Allison, Bingliang Fang, Jianjun Zhang, Heidi Wagner, Elena Bogatenkova, Ignacio Wistuba, Stephen Swisher, Chantale Bernatchez, Don Lynn Gibbons
Journal: Journal of Thoracic Oncology (2017)
TCR and DNAM Dependent Lysis of Acute Monocytic Leukemia (AMoL) by Vg9Vd2 T Lymphocytes.
Authors: Julie Gertner-Dardenne, Eloise Perrot, Thomas Prebet, Aude Charbonnier, Helene Sicard, Norbert Vey, Daniel Olive
Journal: Blood (2009)
P2.04-009 Tumor Size Did Not Affect Masaoka Staging as Predictors of Recurrence in Thymoma
Authors: Yen-Chiang Tseng, Yih-Gang Goan, Yen-Han Tseng, Chien-Sheng Huang, Wen-Hu Hsu, Han-Shui Hsu
Journal: Journal of Thoracic Oncology (2017)
Vps33b is crucial for structural and functional hepatocyte polarity
Authors: Joanna Hanley, Dipok Kumar Dhar, Francesca Mazzacuva, Rebeca Fiadeiro, Jemima J. Burden, Anne-Marie Lyne, Holly Smith, Anna Straatman-Iwanowska, Blerida Banushi, Alex Virasami, Kevin Mills, Frédéric P. Lemaigre, A.S. Knisely, Steven Howe, Neil Sebire, Simon N. Waddington, Coen C. Paulusma, Peter Clayton, Paul Gissen
Journal: Journal of Hepatology (2017)

In the normal liver, hepatocytes form a uniquely polarised cell layer that enables movement of solutes from sinusoidal blood to canalicular bile. Whilst several cholestatic liver diseases with defects of hepatocyte polarity have been identified, the molecular mechanisms of pathogenesis are not well defined. One example is arthrogryposis, renal dysfunction and cholestasis syndrome, which in most patients is caused by VPS33B mutations. VPS33B is a protein involved in membrane trafficking that interacts with RAB11A at recycling endosomes. To understand the pathways that regulate hepatocyte polarity better, we investigated VPS33B deficiency using a novel mouse model with a liver-specific Vps33b deletion.
MA07.11 Safety and Efficacy of Lorlatinib (PF-06463922) in Patients with Advanced ALK+ or ROS1+ Non-Small-Cell Lung Cancer (NSCLC)
Authors: E. Felip, T. Bauer, Benjamin Solomon, B. Besse, L. James, J. Clancy, K. Klamerus, J.-F. Martini, A. Abbattista, A. Shaw
Journal: Journal of Thoracic Oncology (2017)
P169 Long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis: pooled analysis of 4 clinical trials
Authors: PW Noble, C Albera, L Lancaster, P Hormel, H Hulter, U Costabel
Journal: Thorax (2016)

<h3>Introduction</h3> Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible disease that requires long-term management. The objective of this study was to assess the long-term safety of pirfenidone from a pooled analysis of 4 clinical studies. <h3>Methods</h3> All patients who received pirfenidone (2403 mg/d) in the Phase 3 studies (ASCEND/CAPACITY) and/or the long-term extension study (RECAP) were included in this analysis. Safety outcomes were assessed during the period from the first dose until 28 days after the last dose of pirfenidone in either study. Analyses included the final data from the Phase 3 studies and RECAP (data cut, June 30, 2015). <h3>Results</h3> The pooled population included 1216 patients with a cumulative total exposure of 3366 patient-exposure years. Median pirfenidone exposure was 25.9 months (range, 0–105 months), with a mean dose of 2306 mg/d. 99% of patients reported ≥1 treatment-emergent adverse event (TEAE). 57% of patients reported a serious TEAE (0.51 per patient-exposure year [PPEY]), the most common being IPF (21.5%) and pneumonia (9.3%; <b>Table</b>). TEAEs led to discontinuation in 45% of patients (0.17 PPEY), the most common being IPF (15.9%), rash (1.6%) and nausea (1.6%). Median survival on treatment (or ≤28 days after discontinuation of pirfenidone) was 82.6 months. <h3>Conclusions</h3> The safety findings from this pooled analysis are consistent with the known safety profile of pirfenidone and the underlying disease of IPF.
Clostridium Difficile Infection in Patients Undergoing Hematopoietic Cell Transplantation. Results from the Transplantation Group at the Catholic University Hospital in Santiago, Chile
Authors: Pablo Ramirez, Javier Esteban Pilcante, Patricio Rojas, Daniel M Ernst, Mauricio Sarmiento, Mauricio E Ocqueteau, Pablo A Bertin, Veronica Jara
Journal: Blood (2014)
An Autopsy Case of Idiopathic Myocardial Hypertrophy, the Heart Weight of which indicated 1, 000 gr
Authors: Michio Hashimoto, Kazuo Ueda, Shujiro Aonuma, Masahiro Kikuchi, Motoichi Ishihara
Journal: Circulation (1970)

This report presented a case, a male, 62 years, which having a prominent cardiomegaly, died following an episodes of heart failure for ten years. At autopsy cardiac hypertrophy of 1, 000 gr in weight was found and cause of cardiac enlargement was of unknown etiology. The similarity of pathologic features between this case and idiopathic myocardial hypertrophy from literature, was discussed and 18 cases with the heart weight over 800 gr, in autopsy cases at the Department of Pathology, Kyushu University, were reported.
Public Reporting of Mortality Rates for Hospitalized Medicare Patients
Authors: Jean-Frédéric Lévesque, Kim Sutherland
Journal: Annals of Internal Medicine (2017)

Letters3 January 2017Public Reporting of Mortality Rates for Hospitalized Medicare PatientsJean-Frédéric Lévesque, MD, PhD and Kim Sutherland, MBA, PhDJean-Frédéric Lévesque, MD, PhDFrom Bureau of Health Information, Chatswood, New South Wales, Australia.Search for more papers by this author and Kim Sutherland, MBA, PhDFrom Bureau of Health Information, Chatswood, New South Wales, Australia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0547 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Joynt and colleagues (1) make an important and useful contribution to our knowledge about the role that public reporting can play in improving health care. However, wider experience with public reporting efforts suggests that we should question the overriding tenor of their article and its suggestion that public reporting of mortality data dampens the rate of change.The authors clearly show that the rate of improvement in 30-day mortality has slowed in the United States since public reporting was introduced in 2008. However, to say that “public reporting did not have a major effect on mortality rates ...Reference1. Joynt KE, Orav EJ, Zheng J, Jha AK. Public reporting of mortality rates for hospitalized Medicare patients and trends in mortality for reported conditions. Ann Intern Med. 2016;165:153-60. [PMID: 27239794]. doi:10.7326/M15-1462 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Bureau of Health Information, Chatswood, New South Wales, Australia.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0547. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPublic Reporting of Mortality Rates for Hospitalized Medicare Patients and Trends in Mortality for Reported Conditions Karen E. Joynt , E. John Orav , Jie Zheng , and Ashish K. Jha Public Reporting of Mortality Rates for Hospitalized Medicare Patients Karen E. Joynt , E. John Orav , Jie Zheng , and Ashish K. Jha Metrics 3 January 2017Volume 166, Issue 1Page: 75KeywordsDeath ratesHip fracturesIschemic strokeMedicareMortalityMotivationPneumoniaQuality improvementResearch designSurgery ePublished: 3 January 2017 Issue Published: 3 January 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
P1.05-073 Evaluation of Stage 1 Sub-Solid Lung Nodules Using PET Imaging
Authors: Benjamin Tran, Daniel Nicastri, Rowena Yip, Kunwei Li, Dongming Xu, Mary Beth Beasley, Mary Salvatore, David Yankelevitz, Claudia Henschke, Raja Flores
Journal: Journal of Thoracic Oncology (2017)
P2.01-046 Quantitative Measurement of B7-H3 Protein Expression and Its Association with B7-H4, PD-L1 and TILs in NSCLC
Authors: Mehmet Altan, Vasiliki Pelekanou, Kurt Schalper, Maria Toki, Roy Herbst, David Rimm
Journal: Journal of Thoracic Oncology (2017)
P34 Long term outcomes for patients with pulmonary arteriovenous malformations considered for lung transplantation
Authors: CL Shovlin, JMB Hughes, M Layton, E Boother, DJ Allison, JE Jackson
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Pulmonary arteriovenous malformations (PAVMs) are abnormal vessels that provide anatomic right-to-left shunts, and frequently result in severe hypoxaemia. Lung transplantation is sometimes considered if PAVMs are not amenable to treatment by embolization or surgical resection. <h3>Methods</h3> A retrospective review was performed of patients with PAVMs assessed between 1999 and 2016 at a single UK institution. Characteristics of those considered and referred for lung transplantation assessment were examined. <h3>Results</h3> Between May 1999 and July 2016, 707 patients with PAVMs were reviewed. Six were or had been formally considered for lung transplantation purely for PAVMs, 4 as adults (3 at our institution between 1989–1995), 2 as children. Ages ranged from 2–47 (median 22) years. Four were from the UK, two had been assessed in non UK countries. All had hereditary haemorrhagic telangiectasia (HHT). Three had suffered a cerebral abscess due to their PAVMs. The adults had undergone maximal embolisation of PAVMs, and the children were considered to have untreatable disease. The median SaO<sup>2</sup> was 79% on air. One adult underwent lung transplantation overseas and died peri-operatively. The other five were not transplanted, in four cases at the patients’ request. Currently, their survival post assessment for lung transplant ranges from 15 to 27 (median 22) years, with four of the five still alive. All five maintained arterial oxygen content by marked secondary erythrocytotic responses when not iron deficient. Four had subsequent embolisation treatments. One had three successful pregnancies, and another is working full time with no supplementary oxygen. However, two had a cerebral abscess (one fatal); three had deep vein thromboses; two experienced long term disabling pain attributed to hypertrophic pulmonary osteoarthropathy in one; and three have exercise limitation requiring supplementary oxygen. Antiplatelet therapy was recommended for two due to ischaemic strokes; one remains anticoagulated 16 years after the insertion of a caval filter; and one is regularly evaluated for hyperviscosity symptoms that would precipitate isovolaemic venesection. <h3>Conclusion</h3> Very long term stability is evident in the five patients who did not receive a lung transplant. The cohort remain at high risk of cerebral abscess and other complications of right-to-left shunting.
OA03.02 Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study
Authors: Marina Garassino, Naiyer Rizvi, Benjamin Besse, Pasi Jänne, Daniel Christoph, Solange Peters, Chee Keong Toh, Takayasu Kurata, Enric Carcereny Costa, Marianna Koczywas, Enriqueta Felip, Jamie Chaft, Jiaheng Qiu, Marcin Kowanetz, Shelley Coleman, Simonetta Mocci, Alan Sandler, Scott Gettinger, Melissa Johnson
Journal: Journal of Thoracic Oncology (2017)
Endoscopic diagnosis of antral webs in children
Authors: Julia Fritz, Alfonso Martinez, Marjorie Arca, Diana Lerner
Journal: Endoscopy (2017)

An antral web is a rare cause of obstructive symptoms with an unknown prevalence. It was first described in children in 1957, and there remains limited description of these anatomic anomalies in the literature [1] [2] [3]. Diagnosis may be delayed due to nonspecific symptoms and variable presentation. Upper gastrointestinal barium study is currently the standard investigation for evaluation, although diagnosis at the time of surgical intervention is not uncommon [1] [4] [5]. Children with an antral web may also undergo endoscopic evaluation that fails to diagnose the abnormality [4] because of a low level of suspicion and insufficient clinical training to identify this rare anomaly.
In Vitro Generation of Human T-Cell Precursors From Bone Marrow CD34+ Cells by Short Exposure to Immobilized Notch-Ligand Delta-Like 4.
Authors: Christian Reimann, Liliane Dal-Cortivo, Brigitte Ternaux, Emmanuelle Six, Julien Rouiller, Marina Cavazzana-Calvo, Isabelle Andre-Schmutz
Journal: Blood (2009)
P100 Pre-transplant C-Reactive Protein (CRP) as a marker of post-transplant outcomes in patients with Cystic Fibrosis (CF)
Authors: A Fazleen, J Parmar
Journal: Thorax (2016)

<h3>Introduction</h3> Although novel therapies for CF have been introduced, the condition still has a high rate of complications and early death. Transplantation remains the only hope for extended survival and quality of life. Our study aimed to determine whether pre-transplantation CRP could predict outcomes post-transplantation. <h3>Methods</h3> In a retrospective analysis of all lung transplantations performed at our centre between 2001 and 2016, only patients who had complete data were analysed. CRP levels within 72 hours pre-transplantation were compared with length of intubation, ITU and hospital stay, Primary Graft Dysfunction (PGD), pulmonary infection within 3 months post-transplantation and rates of acute cellular rejection. <h3>Results</h3> Among 100 patients who underwent lung or heart/lung transplantation, 72 patients had a complete dataset. Average age at transplantation was 28.1 in both groups. 48 patients had CRP &lt; 40 mg/L (24 males, 24 females, median CRP 14), and 24 patients had CRP &gt; 40 mg/L (14 males, 10 females, median CRP 60). Average age of donor was 41.6 in the low CRP group, and 41.8 in the high CRP group. Average duration of intubation was 66.7 hours in the low CRP group, versus 48.0 hours in the high CRP group, while average length of ITU stay was 6.9 days in the low CRP group, versus 9.3 days in the high CRP group (p 0.76). Average duration of hospital stay was 26.3 days in the low CRP group, and 25.7 days in the high CRP group. Mean number of infections in the low CRP group was 2.4, and 3.3 in the high CRP group (p 0.52). Mean number of episodes of rejection was 0.4 in the low CRP group, and 0.6 in the high CRP group (p 0.36). Kaplan-Meier plots showed no evidence of impact on survival to 5 years. <h3>Conclusion</h3> CRP within 72 hours pre-transplantation in patients with CF was not a predictor of short- or long-term outcomes in our study. It is important to note that the sample size for this study was quite small, possibly contributing to this finding. Extension of this study to include patients from multiple transplant centres would be beneficial.
A Comprehensive Deep-Sequencing Study of Blast Crisis Chronic Myeloid Leukemia (CML) Reveals New Insights Into Molecular Heterogeneity and Detects Mutations In 12 Different Genes In 82.5% of Cases
Authors: Vera Grossmann, Christiane Eder, Sonja Schindela, Alexander Kohlmann, Sandra Wille, Susanne Schnittger, Wolfgang Kern, Martin C. Müller, Andreas Hochhaus, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2010)
OA23.06 Overall Survival (OS) of EGFR Mutation Positive Non-Small Cell Lung Cancer Patients: Real-World Treatment Patterns of 1,660 Japanese Patients
Authors: Kazushi Yoshida, Yuichiro Ohe, Akira Inoue, Toru Kumagai, Masayuki Takeda, Nobuyuki Yamamoto, Takashi Seto, Isamu Okamoto, Naoki Tashiro, Satoshi Morita, Masahiro Fukuoka
Journal: Journal of Thoracic Oncology (2017)
Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice
Authors: Malte Kölling, Tamas Kaucsar, Celina Schauerte, Anika Hübner, Angela Dettling, Joon-Keun Park, Martin Busch, Xaver Wulff, Matthias Meier, Kristian Scherf, Nóra Bukosza, Gábor Szénási, Mária Godó, Amit Sharma, Michael Heuser, Peter Hamar, Claudia Bang, Hermann Haller, Thomas Thum, Johan M. Lorenzen
Journal: Molecular Therapy (2017)

Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells. miR-21-mediated repression of Cdc25a and Cdk6 resulted in impaired cell cycle progression and subsequent mesangial cell hypertrophy. miR-21 increased podocyte motility by regulating phosphatase and tensin homolog (Pten). miR-21 antagonism in vitro and in vivo in streptozotocin-induced diabetic mice decreased mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria, and fibrotic- and inflammatory gene expression. In conclusion, miR-21 antagonism rescued various functional and structural parameters in mice with diabetic nephropathy and, thus, might be a viable option in the treatment of patients with diabetic kidney disease.
P1.03-018 FDG-PET/CT in Patients with EGFR-Mutated NSCLC Treated with TKI. Can We Identify Early Lesions at Higher Risk of Progression?
Authors: Gegory Petyt, Dimitri Bellevre, Amaury Adens, Hélèné Lahousse, Guillaume Collet, Claude Hossein-Foucher, Simon Baldacci, Xavier Dhalluin, Marie-Capucine Willemin, Anne Baranzelli, Arnaud Scherpereel, Alexis Cortot
Journal: Journal of Thoracic Oncology (2017)
P2.03b-094 Prognostic Value of Serum Carcinoembryonic Antigen during Conventional Chemotherapy in Advanced (Non-)Small Cell Lung Cancer
Authors: C. De Jong, I. Gordijn, J.C. Kelder, B. Naaijkens, V.H.M. Deneer, G.J.M. Herder
Journal: Journal of Thoracic Oncology (2017)
P218 The development and psychometric validation of the early morning symptoms of copd instrument (EMSCI)
Authors: A Hareendran, E Zaiser, B Make, E Garcia Gil
Journal: Thorax (2016)

<h3>Introduction</h3> In patients with Chronic Obstructive Pulmonary Disease (COPD), symptoms in the early morning have been reported as being the most troublesome and can negatively impact quality of life. This abstract summarises the development and psychometric testing of the Early Morning Symptoms of COPD Instrument (EMSCI) designed to collect data to evaluate COPD patients’ experiences early in the morning. <h3>Methods</h3> Following a literature review and clinical expert interviews, four focus groups were conducted to identify initial concepts and develop draft items for the EMSCI. One-on-one cognitive debriefing interviews were conducted with 10 COPD patients to confirm item readability, and comprehensiveness. Data from a clinical trial [AUGMENT] in COPD patients (N = 1663) was used for item analyses to inform item-reduction and scoring; and to evaluate psychometric properties. Test-retest reliability was assessed using intra-class coefficient (ICC). Correlations with baseline assessments including the SGRQ, E-RS, and FEV1 were used to evaluate concurrent validity. <h3>Results</h3> Focus group participants (n = 27, mean age = 68.1 y) reported mucus/phlegm (80%), shortness of breath (52%), coughing (48%), tightness in chest (24%), wheezing (8%) and chest congestion (8%) as the most common early morning symptoms. Limitations to activities and rescue medication use in the early morning were reported by 56% and 24% respectively. Cognitive interviews of early versions of the EMSCI suggested the items were comprehensive, relevant and interpreted as intended. Analyses of EMSCI data collected in the Phase 3 trial confirmed a one-factor structure for the symptom severity items. Reliability was confirmed for the 6-item symptom severity (ICC = 0.84), overall symptom severity (ICC = 0.84), activity limitation (ICC = 0.85), and rescue medication (ICC = 0.62) scores. Concurrent validity (Table 1) was supported by positive correlations with both the SGRQ and the E-RS scores. <h3>Conclusions</h3> The EMSCI is a reliable and valid instrument that was developed based on patients’ experiences to evaluate early morning symptoms and impacts of COPD. It is available to be used for clinical decision making and as a clinical study endpoint for the evaluation of new treatments.