tbuckley/cabot-search huggingface dataset:
Abstract LB-184: Bmi1 regulates cell fate via tumor suppressor <i>WWOX</i> repression in small cell lung cancer cells
Authors: Masaki Kimura, Nobuhiro Akita, Hisanori Takenobu, Hideki Kimura, Akira Nakagawara, Takehiko Kamijo
Journal: Cancer Research (2011)

Abstract Mortality from lung cancer is important worldwide. Recently, epigenetic aberration of lung cancer, not only genomic DNA methylation but also chromatin modification, has become an important target for lung cancer research, although previous research has demonstrated that lung cancer develops as a result of both environmental and genetic factors. Here, we demonstrated that an epigenetic regulator/polycomb group protein Bmi1 is more highly expressed in small cell lung cancer than in non-small-cell lung cancer by immunohistochemical analysis. In vitro experiments indicated that Bmi1 reduction by lentivirus-derived shRNA significantly suppressed proliferation, colony formation, and in vivo tumor formation. Importantly, apoptosis was induced by Bmi1 depletion in small cell lung cancer cells. Furthermore, a tumor suppressor WWOX was identified as a Bmi1 target in the cells by chromatin immunoprecipitation assay and quantitative real-time PCR assay; WWOX had a role as a tumor suppressor in SCLC cells; therefore, the Bmi1/WWOX pathway could be a new candidate for a new therapeutic approach for small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-184. doi:10.1158/1538-7445.AM2011-LB-184
Idiopathic Dilated Cardiomyopathy
Authors: G. William Dec, Valentin Fuster
Journal: New England Journal of Medicine (1994)

Idiopathic dilated cardiomyopathy (IDC) is a primary myocardial disease of unknown cause characterized by left ventricular or biventricular dilatation and impaired myocardial contractility1. Depending on the diagnostic criteria used, the reported annual incidence varies between 5 and 8 cases per 100,000 population25. However, the true incidence is probably underestimated by those figures, since many asymptomatic cases remain unrecognized. The age-adjusted prevalence of IDC in the United States averages 36 cases per 100,000 population,5 and it accounts for 10,000 deaths annually2.Blacks and males have a 2.5-fold increase in risk, as compared with whites and females, that . . .
The Value of Fused SPECT/CT in the Evaluation of Solitary Skull Lesion
Authors: Isis W. Gayed, E. Edmund Kim, John Awad, Usha Joseph, David Wan, Susan John
Journal: Clinical Nuclear Medicine (2011)

The aim of this study was to evaluate the role of single photon emission computed tomography and/or computed tomography (SPECT/CT) in differentiating metastatic from benign solitary skull lesions.Consecutive patients who had a SPECT/CT of the head subsequent to a whole-body bone scan (WBS) for the evaluation of a single skull lesion were selected. A single skull lesion on the WBS was further evaluated with SPECT/CT to characterize the lesion. The results of the SPECT/CT were correlated with other radiologic examinations performed within 2 weeks. An average follow-up interval after the SPECT/CT was 8.9 months to correlate with additional radiologic imaging studies and clinical information.A total of 19 lesions in 19 patients were seen on the WBS and 2 additional lesions on the SPECT/CT. All lesions demonstrated focal increased tracer uptake. The SPECT/CT correctly identified 3 out of 3 metastatic lesions and 12 out of 17 benign lesions, that is 71% of lesions were correctly classifised as metastatic or benign lesions. Only 1 patient was classified incorrectly as metastatic lesion with SPECT/CT when it was proven benign by other imaging modalities and follow-up. The sensitivity, specificity, positive and negative predictive values of SPECT/CT images in identifying metastatic lesions were 100%, 92%, 75%, and 100%, respectively. Five lesions remained indeterminate even after the SPECT/CT interpretation and were confirmed benign by other imaging modalities.SPECT/CT can help identify benign versus metastatic solitary skull lesions in most of the patients with high sensitivity and specificity.
Direct Lymphatic Drainage From a Melanoma on the Back to Paravertebral Lymph Nodes in the Thorax
Authors: ROGER F. UREN, ROBERT HOWMAN-GILES, JOHN F. THOMPSON
Journal: Clinical Nuclear Medicine (1999)

Preoperative lymphoscintigraphy with Tc-99m antimony sulfide colloid was performed in a patient with cutaneous melanoma on the lower back just to the right of the midline. There was direct lymphatic drainage to paravertebral nodes in the chest on the right side at the level of the sixth and seventh thoracic vertebrae. There was also drainage directly to the right groin and via a series of interval nodes to the right axilla. Knowledge of the presence of such drainage may influence the surgical management of patients.
Tobacco use among individuals presenting for cancer risk assessment
Authors: W. Shen, L. F. Ross, L. Patrick-Miller, O. I. Olopade, S. A. Cummings, M. A. White, L. Dudlicek, A. R. Bradbury
Journal: Journal of Clinical Oncology (2007)

1547 Background: An important component of cancer risk assessment (CRA) is the evaluation of exposures and preventive health behaviors. Tobacco use (TU) remains a significant contributor to cancer risk and decreasing tobacco use is a major national health objective. Methods: Clinical charts were reviewed to evaluate the incidence of TU and characteristics of tobacco users (TUs) among individuals presenting to the University of Chicago Cancer Risk Clinic for cancer risk assessment (CRA). Results: Among 98 individuals (97% female) presenting for CRA from 12/05–10/06, 51% (50/98) reported no TU, 38% (37/98) reported prior TU and 11% (11/98) reported current TU. Current tobacco users included 10% (7/73) of whites and 18% (4/22) of blacks with no TU among other racial groups (0/3). 45% of TUs (5/11) had a personal history of cancer. 45% of TUs reported compliance with self-breast examination, 73% with cervical cancer screening. Among TUs over 40 years old (YO), 67% (6/9) reported a mammogram in the last year and the 2 TUs over 50 YO reported a screening colonoscopy. All TUs reported interest in tobacco cessation interventions. Conclusions: Tobacco use among individuals presenting for CRA is lower than reported general population rates of TU (23%). Despite this, a proportion of individuals presenting for CRA report current TU, despite engaging in other cancer prevention behaviors. Continued review of clinical encounters from 2004- 06 (n=425) will allow for multi-variate analysis of predictors of current TU, which will inform future research employing cancer risk assessment encounters as “teachable moments” to optimize tobacco cessation outcomes. No significant financial relationships to disclose.
P36 An Advanced Physiological Monitoring Tool To Detect Treatment Failure In Hospitalised Patients With Acute Exacerbation Of Chronic Obstructive Pulmonary Disease (AECOPD)
Authors: ES Suh, S Mandal, MC Ramsay, R Harding, A Thompson, J Moxham, N Hart
Journal: Thorax (2012)

<h3>Background</h3> Acute exacerbations of COPD are associated with significant mortality and morbidity. Hospitalised patients with AECOPD often deteriorate symptomatically despite treatment. We have developed 2<sup>nd</sup> intercostal space parasternal EMG (EMG<sub>para</sub>) as a measure of neural respiratory drive (NRD), with the aim of detecting clinical change in such patients. We hypothesised that change in NRD would be able to detect treatment failure in an unselected cohort of AECOPD patients. <h3>Methods</h3> Patients with AECOPD were recruited at a central London teaching hospital within 12 hours of admission. Patients underwent EMGpara, spirometry and measurement of inspiratory capacity at least daily until medically fit for discharge. Modified Borg scale was recorded with each EMGpara acquisition. We assessed improvement and deterioration by two measures: 1) the responsible medical team was asked to report any deterioration or improvement in the patients’ condition during the course of admission <i>(Leidy et al, AJRCCM 2011)</i>; and 2) 2-point changes in Borg score were recorded as representing significant deterioration or improvement in dyspnoea <i>(Ries et al, COPD; 2005)</i>. Changes in EMGpara%max and neural respiratory drive index (ΔNRDI, where NRDI= EMGpara%max x respiratory rate) <i>(Murphy et al, Thorax; 2011)</i> during episodes of deterioration or improvement were analysed. <h3>Results</h3> 65 patients were recruited. At admission, age was 71±10 years, male 46.2%, FEV1%predicted 32±15% (n=34), body mass index (BMI) 25.6±7.7 kg/m2, length of hospital stay 4 (IQR 2–5.75) days, admission COPD assessment tool (CAT) score 29 (IQR 25–33). There were 66(83%) episodes of improvement and 14(17%) episodes of deterioration as defined by <i>physician opinion</i>. There was a difference in the change in EMGpara%max between episodes of improvement and deterioration (ΔEMGpara%max= –2.00% <i>vs</i> +4.99%, p=0.01; ΔNRDI= –53/min <i>vs</i> 117/min, p=0.02). There were 54(65%) episodes of improvement and 29(35%) episodes of deterioration as defined by a <i>2-point change on the Borg scale.</i> Again there was a difference in neural drive measures between improvers and deteriorators (ΔEMGpara%max= –3.94% <i>vs</i> +2.72%, p=0.002; ΔNRDI= –108/min <i>vs</i> 74/min, p&lt;0.001) (Figure 1). <h3>Conclusions</h3> Neural respiratory drive, as measured by parasternal muscle EMG, is effective in the detection of improvement and deterioration during AECOPD, and demonstrates potential as a physiological biomarker to monitor clinical change.
BT-05 * FUNCTIONAL DIVERSITY AND CO-OPERATIVITY OF SUBCLONAL POPULATIONS OF PAEDIATRIC GLIOBLASTOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA CELLS
Authors: M. Vinci, A. Burford, K. Taylor, V. Molinari, S. Popov, W. Ingram, A. Moore, M. Monje, M. Alonso, J. Pears, N. Entz-Werle, C. de Torres, O. Cruz, J. Mora, A. M. Carcaboso, A. Mackay, C. Jones
Journal: Neuro-Oncology (2015)

A major challenge to improve outcomes in paediatric GBM and DIPG is their extensive intratumoral heterogeneity, reflected by differing cellular morphologies and genomic imbalances present within an individual sample. This is apparent also at the mutational level, where a complex subclonal architecture can be inferred from bulk tumour sequencing at diagnosis/biopsy and at relapse/autopsy. Spatial heterogeneity is also observed by studying multiple topographically distinct regions from the same tumour. We sought to understand the relative functional contributions of these subclonal cell populations to tumour development and evolution. We have established 20 primary patient-derived cultures (10 pGBM, 10 DIPG), with extensive phenotypic and genomic characterisation to ensure accurate recapitulation of the original disease. Single cells were flow-sorted into individual wells in a 96-well format and allowed to form colonies under stem cell conditions on laminin-coated plates (2D) or as neurospheres (3D). Individual colonies were subjected to high-throughput image analysis and targeted re-sequencing. Clonogenicity ranged from 0-20%, significantly higher in H3.3K27M mutant cells. Such an approach allowed for the isolation of single stem cell-derived colonies harbouring clonal mutations, some of which were present in only a small proportion of the original sample, such as a truncating mutation in the histone H4K20 methyltransferase SUV420H1 in a DIPG sample, originally found in 2/678 reads by targeted resequencing. Comparing colonies harbouring this mutation with their ‘natural isogenic’ counterparts with an otherwise identical genetic background, we observed significantly increased invasion and migration in the SUV420H1 mutant cells. Notably, bulk cultures containing mixtures of these distinct subpopulations were found to have additionally enhanced pro-tumorigenic potential than either colony alone. These data identify a distinct genetic and functional diversity in paediatric glioma stem cell populations, and suggest a co-operativity of tumour subclones. Treatment strategies aimed at disrupting these interactions may represent a novel therapeutic approach in these diseases.
Abstract 35: Genome-wide molecular profiling of peri-tumoral neocortex revealed genes possibly responsible for tumor-induced epilepsy
Authors: Xiaojin Li, Jun Xu, Xuemo Fan, Charles E. Niesen, Charles Wang
Journal: Cancer Research (2011)

Abstract Epilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. The molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. Since the alteration in the peritumoral microenvironments is believed to play a significant role in inducing the epileptic state, we hypothesize that the change in gene expression of neighboring astrocytes and neurons may contribute to the increased neuronal excitability. To identify the genes possibly responsible for tumor induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from 1-5 year old formalin-fixed paraffin embedded (FFPE) peritumoral cortex from 5-paired (seizure vs. non-seizure) low grade brain tumor patients. RNAs were extracted from 3-5 microdisections of FFPE tissue blocks using Qiagen RNeasy FFPE kit and cDNA were synthesized and amplified using NuGen's WT-Ovation FFPE RNA amplification system and FL-Ovation cDNA biotin module. Our results showed that although FFPE derived RNAs were significant fragmented with a peak of 100-200 bases, gene detection rate was found to be significant high (up to 49.8%) with excellent 3’/5’ ratios (GAPDH, 1-3.4). The rate of gene detection is depending on the archive time of tissue blocks (correlation coefficient = -0.71, P&amp;lt; 0.05). We identified 345 differentially expressed genes (DEGs, 2-fold plus P &amp;lt; 0.05). Principal Component Analysis (PCA) based on both global genes and 345 DEGs showed that epilepsy samples were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy samples. Gene Ontology (GO) analysis on 345 DEGs revealed several important functional groups of genes including signal transduction (20.6%), metal ion binding (18.2%), cation binding (17.9%), receptor activity (10.8%) and receptor binding (4.0%). Other significant DEGs include transcription factors, glutamate receptors and intercellular matrix proteins. Pathway analysis showed these 345 DEGs were mainly involved in focal adhesion (12 genes), ECM-receptor interaction (11 genes) and cell communication (9 genes) pathways. In conclusion, our study showed that (1) archival FFPE brain tissue is an excellent resource for genomic studying; and (2) the altered gene expression in the peri-tumoral neurons implicate multiple cellular pathways in the induction of the epileptic state. Identification of genes responsible for brain tumor-induced epilepsy may lead to novel and better management of epilepsy in brain tumor patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 35. doi:10.1158/1538-7445.AM2011-35
AB0485 Golimumab’s efficacy in patients with very active disease in methotrexate-naÏve rheumatoid arthritis
Authors: P. Emery, R. Fleischmann, E.C. Hsia, S. Xu, W. Xu, D. Baker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess golimumab (GLM) treatment effect in patients with rheumatoid arthritis (RA) naïve to methotrexate (MTX) therapy with severe, active and progressive disease. <h3>Methods</h3> The GO-BEFORE trial studied GLM 50mg and 100mg + MTX in MTX-naïve patients. In the overall GO-BEFORE study population, patients exhibited lower disease activity (baseline ACR components and DAS28) than was observed in previous studies of biologic agents in MTX-naive patients<sup>1</sup>. This is a retrospective analysis of GO-BEFORE wk 52 data which compares efficacy outcomes in subsets of RA patients with severe, active disease to the overall study population. 637 MTX-naïve pts were randomized to PBO+MTX (Grp 1), GLM 100mg+PBO (Grp 2), GLM 50mg+MTX (Grp 3), or GLM 100mg+MTX (Grp 4). GLM/PBO received injections q4wks. Pts with 5.1, and CRP ≥3 mg/dL. Treatment effect for each subset and the overall population was defined as the differences between GLM 50mg or 100mg +MTX and MTX-alone in ACR50, DAS28 (CRP) remission, change in HAQ ≥0.25 and total vdHS score ≤0. Differences in the treatment effect between each subset of severe, active and progressive RA and the overall population was examined. <h3>Results</h3> Greater proportions of patients achieved the efficacy endpoints in the GLM+MTX groups versus MTX-alone and the difference between the treatment groups (tx effect) was generally larger in the severe, active and progressive subsets compared with the overall population (Table). <h3>Conclusions</h3> Overall, treatment effect in the efficacy parameters between GLM 50mg +MTX and GLM 100mg +MTX versus MTX-alone was greater for the severe, active and progressive subsets versus the overall population. <h3>References</h3> Emery et al. Arthritis &amp; Rheumatism 2009;60(8):2272-2283. <h3>Disclosure of Interest</h3> P. Emery Grant/Research support from: Investigators for Janssen Research &amp; Development, LLC sponsored clinical study, R. Fleischmann Grant/Research support from: Investigators for Janssen Research &amp; Development, LLC sponsored clinical study, E. Hsia Employee of: Janssen Research &amp; Development, LLC, S. Xu Employee of: Janssen Research &amp; Development, LLC, W. Xu Employee of: Janssen Research &amp; Development, LLC, D. Baker Employee of: Janssen Research &amp; Development, LLC
THU0269 Spinal and sacroiliac inflammation as detected by magnetic resonance imaging in patients with ankylosing spondylitis, before and after 12 weeks therapy with non-steroidal anti-inflammatory drugs
Authors: E. Tyukhova, A. Smirnof, O. Rumyanceva, A. Bochkova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the inflammatory lesions of the spine and the sacroiliac joints (SIJ) as detected by magnetic resonance imaging (MRI) in patients (pts) with ankylosing spondylitis (AS) during 12 weeks treatment NSAIDs for the first time on daily basis. <h3>Methods</h3> Thirty consecutive patients (pts) meeting the modified NY criteria AS were studied. MRI (T2 STIR and T1 MRI sequence, General Electrics, 0.35T, matrix 288×192) of the most painful segment of spine and SIJ were performed at baseline (TP0) and after 12 weeks treatment NSAID's (TP1). For assessing active spinal lesions we used the scoring system modified ASspiMRI-a, and for SIJ - Leeds scoring system. MR images were evaluated independently by 2 readers and one of them was blinded to the treatment allocation and time sequence of the images. <h3>Results</h3> Median pts age was 32.5±6.8 yrs, 24 (80%) male, median disease duration was 8.8±5.4 yrs; 29 (96.6%) pts were HLA-B27 positive. Lumbal spine MRI were performed in 19 pts, thoracic spine - in 11 pts. ASAS-NSAID Index 12 weeks satisfied 100 (indometacin 150mg/day (n=6), diclofenac 100-150mg/day (n=14), nimesulide 200mg/day (n=6), meloxicam 15mg/day (n=3), etoricoxib 120 mg/day (n=1)). BASDAI ≥4.0 at TP0 had 16 pts (53.3%), at TP1 – 10 pts (33.3%). Mean the most painful segment of spine level at TP0 was 4.8±2.3, at TP1 - 2.6±2.3, p =0.00001. Spinal inflammation regression was seen after 12 weeks but was not reliable (mean (SD) 2.80±2.55 at TP0 vs 2.26±2.16 at TP1; p =0.20). Regression of active SIJ lesions also was not reliable (mean (SD) 2.80±2.65 at TP0 vs 2.23±2.03 at TP1; p =0.083). MRI spinal lesions disappeared in 2 pts (6.6%) after 12 weeks NSAIDs therapy but in one pt its appeared de novo. MRI SIJ lesions disappeared in 5 pts (16.6%) after 12 weeks NSAIDs therapy but in one pt its appeared de novo. <h3>Conclusions</h3> NSAIDs decreased the level of pain in the spine. NSAIDs for 12 weeks was not effective enough for reducing imaging evidence of disease activity in patients with MRI determined inflammatory lesions. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-205: Identification of tumorigenic cells in KrasG12D-induced lung adenocarcinoma
Authors: John Yu, Huan-Chieh Cho
Journal: Cancer Research (2012)

Abstract We established an inducible KrasG12D-driven lung adenocarcinoma in CCSP-rtTA/TetO-Cre/LSL-KrasG12D mice that enable pursuits of the cellular and molecular processes involved in Kras-induced tumorigenesis. To investigate the cellular origin of this cancer, we first report a strategy using FACS fractionation that could highly enrich bronchiolar Clara and alveolar type II cells, respectively. The EpCAM+MHCII− cells (bronchiolar origin) were more enriched with tumorigenic cells in generating secondary tumors than EpCAM+MHCII+ cells (alveolar origin) in primary tumors that had been already initiated with oncogenic Kras activation. In addition, secondary tumors derived from EpCAM+MHCII− cells showed diversity of tumor locations compared to those derived from EpCAM+MHCII+ cells. In the alveolar region, secondary tumors from EpCAM+MHCII− cells expressed not only bronchiolar epithelial marker, panCK, but also differentiation marker, proSPC, consistent with the notion that cancer-initiating cells display not only the abilities for self-renewal but also the features of differentiation to generate heterogeneous tumors with phenotypic diversity. Furthermore, high level of ERK1/2 activation and colony-forming ability as well as lack of Sprouty-2 expression were also observed in EpCAM+MHCII− cells. Therefore, these results suggest that bronchiolar Clara cells are the origin of cells and tumorigenesis for KrasG12D-induced neoplasia in the lungs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-205. doi:1538-7445.AM2012-LB-205