tbuckley/cabot-search huggingface dataset:
Abstract 1508: SLPI enhances the expression of PLSCR1 in the HEY-A8 ovarian cancer cell line
Authors: Gary H. Altwerger, Jasmine J. Han, Elise C. Kohn, Minshu Yu
Journal: Cancer Research (2011)

Abstract Secretory leukocyte protease inhibitor (SLPI) is a secreted protease inhibitor that governs inflammation and whose importance has been demonstrated in both pathologic and non-pathologic states. We have defined SLPI as an influential component of the tumor microenvironment promoting growth, survival, and tumor aggressiveness in ovarian cancer. Extracellular SLPI interacts with progranulin, an ovarian cancer growth factor and parental molecule of the pro-inflammatory granulins. Recently, intracellular SLPI has been shown to bind to the cytosolic domain of phospholipid scramblase 1 (PLSCR1) in CD4 T-cells. PLSCR1 is a ubiquitous transmembrane proinflammatory protein with oncogenic properties. PLSCR1 overexpression has been identified in malignant colorectal cancer and xenograft tumor models with increased metastatic and invasive potential. We hypothesized that SLPI remains cytosolic or reenters the cytosol from the tumor microenvironment where SLPI can influence its intracellular receptor, PLSCR1. Preliminary western blot data demonstrated PLSCR1 protein expression in both OVCAR8 and HEY-A8 human ovarian cancer cells with OVCAR8 expressing far less PLSCR1. OVCAR8 is also known, from previous studies, to express less SLPI than Hey-A8 cells. These data led us to investigate SLPI and PLSCR1 interactions using confocal microscopy where we stained HEY-A8 cells and found colocalization of SLPI and PLSCR1. Using HEYA8 with constitutively forced expression of SLPI and protease inhibitor null mutant Leu71PheSLPI, we examined the effect of SLPI on PLSCR1. The increased secretion of SLPI in these stably transfected cells is associated with increased PLSCR1 expression regardless of protease inhibitor activity; additional mutants are currently under examination. These data suggest a positive feedback mechanism between SLPI and its intracellular receptor, PLSCR1 in human ovarian cancer cells. Inhibition of SLPI, already credentialed as a molecular target in ovarian cancer, may be enhanced by interruption of its effects on PLSCR1. 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 1508. doi:10.1158/1538-7445.AM2011-1508
Abstract 2825: Regorafenib and Sorafenib induce reversible quiescence in human hepatoma cells
Authors: Brian I. Carr, Caterina Messa, Aldo Cavallini, Rosalba D'Allesandro, Maria Grazia Refolo, Catia Lippolis, Angela Tafaro
Journal: Cancer Research (2012)

Abstract The actions of the multikinase inhibitor Sorafenib (Soraf) and its more potent fluoro-analog, Regorafenib (Regoraf) were examined on human Hep3B and PLC/PRF/5 hepatoma cells in vitro. IC50 was 7.5 µM for Soraf and 5.0 µM for Regoraf. Both agents required 48 hr. exposure to cells for maximal growth inhibitory effects measured by MTT at 96 hr. Evidence was found for Regoraf-induced apoptosis (max. 25% by FACS at 48 hr. and 45% decrease in Bcl-2 and BcL-xL), non-classical autophagy (50% increase in Beclin-1, without change in LC3 I/II ratio) and cell signaling changes (decreased p-ERK, increased p-JNK and p-Jun). In addition to growth inhibition, quiescence was observed for up to 6 wk. in the presence of prolonged drug exposure. Furthermore, after 1 wk. of drug-mediated inhibition, removal of either Soraf or Regoraf resulted in normal cell proliferation (recovery), unlike treatment with TGFβ 1µM or doxorubicin 0.1µM for 48 hr., after which no recovery was seen. The data are consistent with multiple mechanisms and pathways being altered during Regoraf-mediated growth inhibition and the induction of both quiescence and recovery after withdrawal of either Soraf or Regoraf, which have clinical implications. 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 2825. doi:1538-7445.AM2012-2825
OP0209 Cluster Analysis to Explore Subclassification of Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss)
Authors: T. Neumann, F. Moosig, A. Vaglio, J. Zwerina, P. Bremer, A. Gioffredi, J. Grosskreutz, C. Kroegel, F. Maritati, M. Resche-Rigon, A. Mahr
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Results from descriptive studies on eosinophilic granulomatosis with polyangiitis (EGPA) hint at distinct clinical subclasses, which might notably be determined by ANCA status. <h3>Objectives</h3> This study explored the possibility of subclassifying EGPA using hierarchical cluster analysis. <h3>Methods</h3> A standardized retrospective dataset from a cohort with clinical diagnoses of EGPA followed in 4 tertiary referral centers was used. Hierarchical cluster analysis using Ward’s method was performed based on the following 12 input variables assessed at diagnosis: constitutional symptoms, mucucutaneous, ophthalmological, ENT, cardiovascular, gastrointestinal, renal, and central nervous involvement, peripheral neuropathy, non-fixed lung infiltrates and ANCA positivity. The resulting clusters were described by their most prominent summary characteristics. In addition, the distribution of clinical variables according to ANCA status was compared with chi-square tests. <h3>Results</h3> The analyzed dataset included 262 EGPA cases diagnosed 1984–2012. ANCA were detected in 30.9%. The cluster analysis produced 3 clusters of respectively 39 (cluster 1), 92 (cluster 2) and 131 subjects (cluster 3). They were characterized as follows: cluster 1 by renal involvement (84.6%) and high ANCA prevalence (92.3%); cluster 2 by virtually absent renal involvement (3.3%) and ANCA (4.3%); and cluster 3 by an intermediate phenotype with renal involvement (13%), presence of ANCA (31.3%) and more frequent cardiovascular (59.5% vs. 17.9% and 35.9% for clusters 1 and 2, respectively) and gastrointestinal involvement (42% vs. 15.4% and 12%). Stratification of the 11 clinical input variables by ANCA status showed that ANCA positivity was associated with renal disease (<i>P</i> &lt; 0.0001), peripheral neuropathy (P = 0.005) and constitutional symptoms (P = 0.02). <h3>Conclusions</h3> Although reinforcing the link between ANCA positivity and renal involvement, the cluster analysis does not suggest that EGPA is composed of clearly separated and mutually exclusive subclasses. <h3>Disclosure of Interest</h3> None Declared
Cervical Lymph Node Sarcoidosis as a Pitfall in F-18 FDG Positron Emission Tomography
Authors: ALEXIUS JOE, STEFAN HOEGERLE, ERNST MOSER
Journal: Clinical Nuclear Medicine (2001)

JOE, ALEXIUS M.D.; HOEGERLE, STEFAN M.D., AND; MOSER, ERNST M.D., Ph.D. Author Information
NI-35 * ESTABLISHMENT OF BRAIN TUMOR PHOSPHOLIPID IMAGING PROFILING BY MALDI MASS SPECTROMETRY - A MOUSE MODEL
Authors: C.-Y. Huang, H.-W. Wu, H.-Y. J. Wang, P.-Y. Chen, K.-C. Wei
Journal: Neuro-Oncology (2014)

Malignant brain tumor is a common and severe primary brain tumor with a high recurrence rate and a poor prognosis. Because of the infiltrative nature of malignant brain tumor, tissues surrounding the tumor that remain after surgery might contribute to recurrence. Develop potential tumor marker profiles may help to distinguish tumor and healthy tissues in the brain. Since aberrant lipid metabolism in tumor cells has been commonly observed in cancer cells, it is likely that the altered lipid metabolism will also be seen in the in situ tumors. To visualize such change, we profiled the phospholipids in the brain tumor created in a mouse model with MALDI-MS. We also visualized the distribution of aberrant phospholipids in the brain tumor by MALDI-MS imaging. The MALDI profiling and imaging were also carried out in sections after desalting to remove the interference from the endogenous alkali metal ions, and reveal additional low abundant lysophospholipids within the tumor. Tumor specific phosphatidylcholine, lysophosphatidylcholine and sphingomyelin distribution also show regional variation within the brain tumor region. Whether the combination of these species can serve as the marker for pathological differential grading requires further verification.
Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide
Authors: Andrew T. Turrisi, Kyungmann Kim, Ronald Blum, William T. Sause, Robert B. Livingston, Ritsuko Komaki, Henry Wagner, Seena Aisner, David H. Johnson
Journal: New England Journal of Medicine (1999)

For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy.
SAT0424 Preliminary Results of the Early Intervention in Patients Being Off Work by Musculoskeletal Causes in the HUP La Fe Area.
Authors: M. D. Garcia-Armario, C. Molina, J. Ivorra, I. Martinez-Cordellat, J. L. Valero, E. Grau, I. Chalmeta, R. Negueroles, L. Gonzalez-Puig, M. L. Muñoz, C. Nuñez-Cornejo, C. Alcañiz, J. A. Roman-Ivorra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In March 2012, a new project was started in the HUP La Fe, following the pilot project performed in San Carlos Clinical Hospital in Madrid, where patients off work for musculoskeletal causes were referred to us from Primary Care. <h3>Objectives</h3> The aim of the study is to analyze the variation in days off work in those individuals included in this program with respect to the normal average of days off. <h3>Methods</h3> Cohort, observational, cross-sectional study from April to December 2012, which included patients from the HUP La Fe area, for the first time referred to the Rheumatology Early Intervention consultation because of temporary disability due to musculoskeletal origin. These patients are referred to medical appointment with a maximum waiting time of one week and were provided of medical treatment, ultrasound articular injections and directed exercises if needed. The patient is reviewed continuously until discharge. We excluded patients whose disabilities were traumatic or surgical, or their situation can cause a permanent disability. <h3>Results</h3> We included a total of 116 patients with a mean age of 49 years and 58% were women. The most frequently reported diseases were: back pain (34%), neck pain (12%), shoulder pain syndrome (9%) and other tendinopathies (10%). The 44.8% of cases had a history of sick leave. 100% of the patients received medical treatment, 31% underwent articular ultrasound, 25% of them with infiltration and 61% were trained to perform physical therapy exercises at home. The pathology that had a higher average number of days from the first visit to the medical discharge were lumbociatalgia (34 days), neck pain (21 days), painful shoulder syndrome (17 days) and low back pain (14 days). Comparing these data with the population controlled pilot study there is a decrease of the days off, being in the control group lumbociatalgia (57.6 days), neck (37.4 days), back pain (34.5 days) and tendinitis (36.7 days). <h3>Conclusions</h3> Preliminary results obtained in our study show that early intervention by rheumatologists in patients with temporary incapacity pathology with musculoskeletal origin decreases the number of days off work, compared to patients treated regularly, and can incorporate to work early and consequently, save all costs resulting from such temporary disability. <h3>Disclosure of Interest</h3> None Declared
Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials
Authors: Qiang Zhou, Ebenezer Daniel, Maureen G. Maguire, Juan E. Grunwald, E. Revell Martin, Daniel F. Martin, Gui-shuang Ying
Journal: Ophthalmology (2016)
Plasma Viremia in Human Immunodeficiency Virus Infection
Authors: Robert W. Coombs, Ann C. Collier, Jean-P. Allain, Beverly Nikora, Michael Leuther, George F. Gjerset, Lawrence Corey
Journal: New England Journal of Medicine (1989)

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P<0.01). Plasma HIV titers ranged from 100 to 104.3 and rose from a mean of 101.4 in asymptomatic patients to 102.5 in those with AIDS (P<0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titer. Follow-up tests Indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious. (N Engl J Med 1989; 321:1626–31.)
PTU-005 Factors Influencing The Quality Of Colonoscopy Training In The North West Deanery
Authors: G Beejooa, N Prasad, P Shields
Journal: Gut (2014)

<h3>Introduction</h3> Endoscopy is integral to the JRCPTB Gastroenterology Curriculum and the JAG clearly defines competencies that must be achieved before independent practice. Training in colonoscopy for Gastroenterology Specialty Trainees (ST) can be challenging due to current work patterns and non-GI commitments. We aimed to evaluate the opportunities for and the quality of colonoscopy training in the NW Deanery as perceived by STs. <h3>Methods</h3> An electronic questionnaire was sent to all Gastroenterology STs enrolled within the NW Deanery including questions based on data which would be available from the JETS e-portfolio. STs were excluded at the point of entering OOP activity. To allow comparison, number of procedures performed was standardised to year of training and to length of time in each post. We used an arbitrary minimum expected number of procedures per year at each level of training to calculate adequacy of training opportunities. <h3>Results</h3> 29 trainees completed the survey (ST3=3, ST4=8, ST5=4, ST6=6, ST7=1, OOP = 7) at 13 sites. 7 (24%) had achieved JAG accreditation for diagnostic colonoscopy. Overall completion rate (CR) was 52.2% (0 to 97%). Mean number of colonoscopies (and independent CR) was: ST3=25.6 (7%), ST4=68.9 (19%), ST5=103.3 (65%), ST6=105.7 (87%), ST7=66 (92%). 5 (17%) STs had a CR of &gt;90% and had performed an average of 270 procedures to attain this level. The average number of colonoscopies per year for each individual site ranged from 34% to 160% of expected procedures. 22 (76%) STs had used a scope guide and 33% of these STs found it useful. 62% of trainees were satisfied with the level of supervision during endoscopy. 62% of trainers had completed a TCT course or equivalent but 14% of STs did not know. The major limiting factor affecting colonoscopy training was GIM commitments (72%) with lists missed due to on call shifts. 41% reported that training lists were not tailored to their needs, 38% missed lists due to lack of ward cover and 38% did not feel that they had enough colonoscopy lists. Other factors affecting colonoscopy training included competition with nurse endoscopists (10%) and trainers taking over too early (14%). 24% of STs rated their satisfaction with colonoscopy training at 4 or 5 (on a scale of 1 to 5, where 1 was poor and 5 was excellent). <h3>Conclusion</h3> There is considerable variability in opportunities and quality of colonoscopy training in the NW Deanery. Service provision must be balanced with a structured, high quality training programme to ensure that colonoscopy performance can meet the mandatory standards expected at the time of CCT. In our region, it is reassuring that STs seem to achieve these targets by ST7 despite the challenges we identified. This study provides a baseline for future quality improvement in NW Deanery colonoscopy training. <h3>Disclosure of Interest</h3> None Declared.
MUTATIONS IN SMOOTH MUSCLE AORTIC ALPHA-ACTIN GENE ARE ASSOCIATED WITH FAMILIAL THORACIC AORTIC ANEURYSM AND DISSECTION
Authors: Nupoor Narula, Eliana Disabella, Valentina Favalli, Alessandra Serio, Maurizia Grasso, Carmelina Giorgianni, Tonia Fiantanese, Takahide Kodama, Eloisa Arbustini
Journal: Journal of the American College of Cardiology (2015)
Lack of Platelet Response to Stimulation in the Wiskott-Aldrich Syndrome
Authors: A. Kuramoto, M. Steiner, M. G. Baldini
Journal: New England Journal of Medicine (1970)

Two striking abnormalities were found in the platelets from three boys with the Wiskott-Aldrich syndrome and their mother: lack of aggregation with epinephrine, and lack of metabolic response to stimulation with polystyrene-latex particles and with epinephrine. Whereas normal platelets reacted with an increase of eight to 12 times in citric acid cycle activity to the addition of polystyrene-latex particles, and with an increase of two to three times to epinephrine stimulation, these metabolic reactions were practically absent in the platelets from the affected children and severely depressed also in the platelets of the mother.
Abstract SY02-03: Bromodomain inhibition in cancer
Authors: James E. Bradner
Journal: Cancer Research (2012)

Abstract Cellular states are maintained by coordinated gene expression programs, attributable to master regulatory transcription factors. Toward the pharmacologic control of cellular states we have undertaken a chemical biological approach to inhibit chromatin-dependent transcriptional signaling. Transcriptional activation by master regulatory proteins is facilitated by chromatin remodeling at promoter/enhancer regions, in particular side-chain acetylation of lysine residues on nearby histone tails. Context-specific lysine acetylation prompts molecular recognition by transcriptional co-activator proteins possessing acetyl-lysine recognition modules, or bromodomains. Perhaps owing to perceptions regarding the feasibility of abrogating protein-protein interactions, research toward the direct inhibition of human bromodomains (or epigenetic reader proteins, in general) has received comparatively little attention. Based on the above rationale, we have developed chemical and biochemical platforms for the development and characterization of novel bromodomain inhibitors. Recently, we reported the first potent, small-molecule inhibitor of human bromodomains, JQ1, which exhibits selectivity for the BET family of bromodomain-containing transcriptional co-activators. Of broad relevance to cancer, we will present research demonstrating that c-Myc expression is critically dependent on BRD4 function and localization to discrete upstream regulatory regions. Exposure of cancer cells to JQ1 prompts immediate down-regulation of c-Myc expression leading to suppression of a transcriptional program associated with proliferation, survival and metabolic adaptation. In translational models of Myc-dependent hematologic malignancies, the efficacy of JQ1 treatment establishes a mechanistic rationale for the leveraged clinical development of drug-like JQ1 derivatives. Toward this objective, we have completed chemical optimization of novel, drug-like inhibitors of BET bromodomains as reagents capable of supporting human clinical investigation. This research has established the feasibility of inhibiting epigenetic reader proteins with efficient, cell-permeable, small molecules. In support of an open-innovation model of chemical biology, we have created a chemical probe allowing the broad study of chromatin biology, which has already been provided to more than 150 academic, governmental and industrial laboratories worldwide. Together, we have rapidly identified mechanism-based opportunities for clinical translation in cancer, inflammation and metabolic diseases. 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 SY02-03. doi:1538-7445.AM2012-SY02-03
S142 Vastus Lateralis Proteomic Analysis In Muscle Wasted Patients With Copd Using Two-dimensional Fluorescent Electrophoresis
Authors: R. A. Rabinovich, R. Lahkdar, E. M. Drost, R. Bastos, W. MacNee
Journal: Thorax (2014)

<h3>Introduction</h3> Muscle wasting, that is present in a subgroup of patients with COPD, is an independent predictor of health related quality of life and survival. The two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology is now recognised as an accurate method to determine and quantify proteins. <h3>Methods and results</h3> With the aim of identifying proteins potentially involved in the process of muscle wasting, we performed 2D-DIGE protein expression profiling in the <i>vastus lateralis</i> of 10 patients with COPD and low fat free mass index (FFMI) (COPD<sub>L</sub>) (FEV<sub>1</sub> 33 ± 4.3%pred, FFMI 15 ± 0.2 Kg.m<sup>-2</sup>) in comparison with both 8 patients with preserved FFMI (COPD<sub>N</sub>) (FEV<sub>1</sub> 47 ± 7.3%pred, FFMI 19 ± 0.6 Kg.m<sup>-2</sup>) and 9 age and gender-matched healthy sedentary subjects (C) (FEV<sub>1</sub> 96 ± 4.0%pred, FFMI 20 ± 0.9 Kg.m<sup>-2</sup>). Data analysis was performed using DeCyder software and for protein identification MALDI_TOF mass spectrometry (MS). Ten proteins, whose expression was significantly changed in COPD<sub>L</sub>, were identified; serum albumin (ALBU), heat shock protein beta-1 (HSPB1), peroxiredoxin-6 (PRDX6), Alpha-crystallin B chain (CRYAB) and Alpha-1-antitrypsin (A1AT) were increased while Histone-lysine N-methyltransferase (DOT1L), Troponin T (TNNT1), Myozenin-1 (MYOZ1), Myosin light chain 1 (MYL1) and mitochondrial ATP synthase subunit alpha (ATPA) were decreased. <h3>Conclusion</h3> Our results showed a down-regulation of structural muscle proteins, proteins involved in myofibrillogenesis, cell cycle arrest and energy production and up-regulation of proteins reacting to cell stress and proteins involved in oxidative stress protection. Supported by Chief Scientist Office (CSO) Scotl<i>06/S1103/5 </i>and FIS <i>PI08/0320</i>.