tbuckley/cabot-search huggingface dataset:
Abstract 1392: Differential effects of Cancer Stem Cells (CSCs) and non-CSCs-targeted therapies on lung primary tumors and metastasis
Authors: Leyre Larzabal
Journal: Cancer Research (2012)

Abstract Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. Salinomycin was recently identified as a selective inhibitor of CSCs. The aim of this study was to investigate the effect of salinomycin with or without combination with paclitaxel in the Lewis lung carcinoma (LLC) metastatic model. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the human H460, H1299 and H272 lung cancer cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. For in vivo experiments, LLC cells were injected subcutaneously and, after surgical removal of the primary tumors, animals were checked for lung metastasis. Paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p&amp;lt;0.05), whereas salinomycin had no effect on primary tumors but reduced metastasis (p&amp;lt;0.05). Combination of both drugs did not improve the effect of single therapies. mRNA levels of ALDH, CXCR4 and SDF-1 were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change) when mice were administered with salinomycin. The number of F4/80+ (macrophages) was also decreased upon administration of paclitaxel or salinomycin in both primary tumors and metastasis. The number of mast cells was only reduced in primary and metastatic lesions of paclitaxel-treated mice. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. On the contrary, paclitaxel (although reducing primary tumor growth) promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster metastasis. 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 1392. doi:1538-7445.AM2012-1392
OUTCOMES IN THE COREVALVE US HIGH-RISK PIVOTAL TRIAL IN PATIENTS WITH A SOCIETY OF THORACIC SURGEONS PREDICTED RISK OF MORTALITY LESS THAN OR EQUAL TO 7
Authors: Michael J. Reardon, David Adams, Neal Kleiman, G. Michael Deeb, Steven Yakubov, George Zorn, Jeffrey Popma
Journal: Journal of the American College of Cardiology (2016)
PTU-132 Carbonated Solutions are Superior to Sour Solutions in Modifying Human Swallowing Reaction time Performance
Authors: O Elshukri, E Michou, S Mistry, S Hamdy
Journal: Gut (2013)

<h3>Introduction Background/Aims</h3> Clinical evidence supports a role for carbonated liquids in reducing aspiration in dysphagic patients compared to simple water (Bulow <i>et al</i> Acta Radiologica, 2003). However, there are limited data on how carbonation modulates swallowing performance. Here, we investigate the effects of equi-pH carbonated and sour (citric acid) water solutions on swallowing performance using a reaction time task (Mistry <i>et al</i> J Physiol.2007), in healthy volunteers. <h3>Methods</h3> Twelve healthy participants (6 male, 33±4 years, mean± SEM) visited the laboratory on three separate occasions. Subjects were asked to perform 5 consecutive measurements of swallowing behaviour with 10 normal,10 fast and 10 challenged swallows per measurement (within a pre-determined time-window). For each task, subjects swallowed each of three solutions: carbonated, sour/citric acid and still water solutions with each attendance in a randomised order. The 5 blocks of 30 swallows were repeated over a 1 hour period at 0 15, 30, 45 and 60 minutes to control for fatigue and practise confounding variables. Measurements were performed through an intra-pharyngeal catheter with built-in pressure transducers to record change in pharyngeal pressure. A pair of electrodes on the back of subject’s hand was used to deliver an electrical pulse to cue the subject when to swallow. Subjects were invited for an additional visit to complete a ‘taste intensity’ questionnaire. Data were analysed with non-parametric Wilcoxon’s test in SPSS16. <h3>Results</h3> Mean swallowing latencies of both normal and fast swallows were not significantly different across the three different sessions. However, for the challenged swallowing task, compared to still water, carbonated water significantly improved the number of correct swallows (Z = –2.044, p = 0.041). By contrast, sour (citric acid) solutions had no effects on challenged swallowing compared water [citric acid*water (Z = –0.045, P = 0.9640)], despite being similar to carbonated water [citric acid*carbonated (Z = –1.293, p = 0.196)]. Carbonated solutions also had the highest intensity score being greater than both sour and still water [carbonated*water (Z = –3.517, P = 0.000), carbonated *citric acid (Z = –3.520, p = 0.000)]. <h3>Conclusion</h3> Carbonation appears to alter swallowing performance compared to other liquids by improvement in complex tasks and showed greatest perceived taste intensity. These data support the using of carbonation as treatment option for dysphagic patients in preventing aspiration and lay the basis for further clinical research with carbonation on swallowing function. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Bulow <i>et al.</i><i></i> Acta Radiologica., 2003 Mistry <i>et al.</i> J Physiol., 2007
Fraud in scientific research – birth of the Concordat to uphold research integrity in the United Kingdom
Authors: Ankur Khajuria, Riaz Agha
Journal: Journal of the Royal Society of Medicine (2013)

Fraud in research has risen exponentially and recent high profile cases may just be the tip of the iceberg. This threatens to have a major impact on public health, with policy makers and clinicians acting on erroneous data. To address this, the new research "Concordat", a consensus statement on research misconduct, has been published. Can it hold the key to rebuilding public confidence in scientific research in the United Kingdom? This review focuses on the concept of research misconduct, highlighting prominent cases and discussing strategies in order to restore confidence in the validity of scientific research.
S80 The role of MyD88 in rhinovirus 1B infection
Authors: C. A. Stokes, E. P. Dick, J. A. Bennett, S. Ismail, M. R. Edwards, I. Sabroe, L. Parker
Journal: Thorax (2010)

Introduction Rhinovirus (RV) are major triggers of acute asthma exacerbations and result in innate immune cell infiltration into the airways. Viral recognition by TLRs results in activation of pathways mediated by the adaptors MyD88 and TRIF, which predominantly control the production of proinflammatory cytokines and interferons respectively. We have previously shown that addition of the cytokine IL-1 (which also signals via MyD88) potentiates responses to the viral mimic Poly (I:C),[1][1] which acts in a MyD88-independent manner. This demonstrates the potential for IL-1signaling to impact on viral infection. In this study, we explored the ability of MyD88 to regulate responses to the natural viral pathogen, RV serotype 1B (RV-1B). Methods MyD88 was stably knocked down in the immortalised bronchial epithelial cell line, BEAS-2B, using a lentiviral transduction system containing shRNA targeted to MyD88. Wildtype or MyD88KD cells were stimulated, in the presence or absence of human monocytes, with TNFα and IL-1β, poly(I:C), LPS and gardiquimod (TLR3, TLR4 and TLR7/8 agonists, respectively), or infected with RV-1B. Selected experiments were carried out in the presence of IL-1ra. Changes in cytokine release were measured by ELISA. Rates of viral replication were measured using quantitative PCR. Results Costimulation of BEAS-2B cells with IL-1 and RV-1B caused a dramatic increase in proinflammatory (CXCL8), but not CCL5 production. MyD88KD cells with ∼70% reduction in MyD88 mRNA levels showed no impairment to TNFα or poly(I:C) stimulation, but significantly reduced responses to IL-1β. MyD88KD cells also had significantly impaired responses to RV-1B as assessed by production of CXCL8 and CCL5. Inhibition of RV-induced CXCL8 production could also be achieved by pre-treatment with the IL-1 antagonist, IL-1ra. IL-1β was not produced from RV-infected cells, implicating other members of the IL-1 family in the response of epithelial cells to viral infection. Viral replication was more marked in MyD88KD cells. Conclusion A reduction in MyD88 signalling modulates specific epithelial cell responses to rhinovirus, and thus may be an important target to control acute inflammation induced by human viral pathogens. ![Abstract S80 Figure 1][2]</img> Abstract S80 Figure 1 [1]: #ref-1 [2]: pending:yes
Abstract 4200: Transgenic mice overexpressing a Claudin-6 tail deletion mutant are resistant to tumor formation
Authors: Kursad Turksen, Azadeh Arabzadeh, Tammy-Claire Troy
Journal: Cancer Research (2010)

Abstract Morphological and physiological observations suggest that the tight junction (TJ)-based permeability barrier is modified/disrupted during tumorigenesis. It is now also widely recognized that the Claudin (Cldn) family of four tetraspan transmembrane proteins is crucial for tight junction assembly and permeability barrier function. However, the detailed roles of the Cldn cytoplasmic tail and extracellular loop domains in these processes or their dysfunction in tumorigenesis are not yet understood. We recently demonstrated that the tail domain of Cldn6 is crucial for membrane targeting and epidermal permeability barrier (EPB) formation, by forced expression of a Cldn6 tail deletion mutant (CDelta187) via the involucrin (Inv) promoter in the suprabasal compartment of the mouse epidermis. Even though a functional barrier formed, Inv-CDelta187 mice displayed histological and biochemical abnormalities in the epidermal differentiation program leading to a thickening of the epidermis after 1 week of age that persisted throughout life. Notably, a significant amount of not only Cldn6, but also Cldn10, Cldn11, and Cldn18 remained cytoplasmically localized and the protein-unfolding pathway was activated in transgenic epidermal cells. Using a well-established two-stage chemical carcinogenesis model, we are now investigating the temporal and spatial changes in expression of these and other (Cldn1, Cldn12) Cldns that we have previously demonstrated to be important in epidermal differentiation and tumorigenesis in CDelta187 versus wild type (WT) mice. METHODS: The lower dorsal backskin of mice was treated topically with 7,12-dimethylbenz(a)anthracene (DMBA; 0.25 mg/ml in acetone) and following a 10-day incubation period, 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 25 microg/ml in acetone) was applied three times a week to the same area. Backskin samples were dissected 2, 4, 6, 8 and 12 weeks after the initiation of the experimental protocol and immunohistochemistry was performed on sections using antibodies against the following: Cldn1, Cldn6, Cldn11, Cldn12, Cldn18, Ki67 (proliferation marker) and CD3 (immune infiltration marker). Strikingly, epidermal tumor formation was inhibited in CDelta187 as compared to WT animals. This is the first demonstration that alterations in Cldn structure and homeostasis may play a protective role against DMBA/TPA-induced skin tumors. Further investigation into the molecular mechanisms underlying this protective function is underway. Supported by CIHR Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4200.
AB1067 Eighteen cases of crowned dens syndrome: Presentation and diagnosis
Authors: M. Godfrin-Valnet, D. Wendling, G. Godfrin, J. Godard, C. Prati, E. Toussirot, F. Michel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Eighteen cases of crowned dens syndrome: presentation and diagnosis. <h3>Objectives</h3> To etablish the clinical, biological and radiological criteria of crowned dens syndrome, a little known etiology of acute neck pain. <h3>Methods</h3> We carried out a retrospective observational study of patients who were treated in our department between 1990 and 2011. <h3>Results</h3> Eighteen cases were recorded. Most of the patients affected (61%) were women, aged over 60 on average (median 75, 5 years). Clinically, the diagnostic triad (neck pain, stiff neck and headaches) was present in 13 out of 18 cases. From a biological point of view, a marked inflammatory syndrome was observed in over half the cases (11 out of 17.64%) with a mean CRP levels of 82.3 mg/l (23 - 275) at admission. Laboratory tests should look for any underlying metabolic disease, especially in patients aged under 50. In our study, the cervical bone CT scan confirmed the suspected diagnosis in 100% of cases. In 44% of cases, calcifications were located on the transverse ligament of the atlas and the alar ligament, in 16.6% calcifications were mottled, and located at the posterolateral surface of the dens. Other imaging tests provided little information, including standard radiographs of the cervical spine. MRI is not able to make a specific diagnosis, but enables us to eliminate differential diagnoses. The numerous differential diagnoses that often lead to additional and unnecessary therapeutic tests are a major problem in crowned dens syndrome. In our study, in over half of the cases, other diagnoses were initially considered, such as: infectious cervical spondylodiscitis, impingement, Horton's disease, polymyalgia rheumatica. Infectious etiologies, spinal inflammatory diseases or other types of inflammatory vasculitis may lead to mistakes due to the stiff neck pain triggered. The standard treatment is based on anti-inflammatory drugs (NSAIDs, colchicine) or corticosteroids. In our series, treatment with colchicines was used as the first-line treatment in 77.7%of cases. These treatments are highly effective: a spectacular recovery ad integrum of cervical mobility may be observed within 48 hours. <h3>Conclusions</h3> Crowned dens syndrome should be known to other medical specialties because it can be cause diagnostic mistake. A comprehensive consultation, a complete clinical examination and a precise analysis of the imaging will avoid unnecessary tests an treatment. <h3>References</h3> Dirheimer Y, Wackenheim A. Crowned odontoid apophysis. Apropos of the development mechanism of certain images of axis manifestations. Sem Hop 1974; 50: 2077-80. <h3>Disclosure of Interest</h3> None Declared
TCT-761 Balloon-Expandable Transcatheter Aortic Valves Can Be Effectively And Safely Implanted Transfemorally Without Balloon Valvuloplasty
Authors: Suneil K. Aggarwal, Nicola Delahunty, Sarah Early, Emmanuel Ako, Mun-Hong Cheang, Markus Reinthaler, Asad N. Tamimi, Bethany Wong, Neil Roberts, John Yap, Muhiddin Ozkor
Journal: Journal of the American College of Cardiology (2014)
SAT0078 The Need to Perform an Impact Study before Using Referral Models for Axial Spondyloarthritis in Daily Practice:
Authors: L. Van Hoeven, Y. Vergouwe, M. Hazes, A. Weel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Unfortunately, only a small part of all published prediction models is used in daily practice, an explanation can be a lack of efficacy or practical feasibility. Therefore prediction modeling research recommends to perform three study phases before using the model in daily practice: (1) developing and internally validating (2) external validation and updating; (3) assessing the model9s impact on decision making and patient outcomes. Axial spondyloarthritis (axSpA) is characterized by a diagnostic delay, the time between the first symptoms and final diagnosis is on average 7-10 years. This delay requires a prediction model that can early identify possible axSpA patients in the large group of chronic low back pain (CLBP) patients. <h3>Objectives</h3> To identify all published prediction models (e.g. referral rule or screening methods) for axial spondyloarthritis (axSpA) and to investigate in which prediction modelling phase this model is. <h3>Methods</h3> Publications describing a prediction model, screening method, or referral rule for axSpA were identified by an Embase and Medline search, at January 29, 2014. After reading all articles we scored which prediction models had been externally validated and whether an impact study had been performed. <h3>Results</h3> In total 11 studies were identified, all presenting a prediction model for axSpA, applicable in patients with CLBP. Ten studies were developing studies and only one study performed an external validation. So far, none of these studies have performed an impact analysis. <h3>Conclusions</h3> Of all published prediction models for axSpA only one has been externally validated. Before using any prediction or referral model for axSpA in daily practice, we advise to perform an impact study to investigate the impact of a prediction model on decision making and patient outcomes <h3>References</h3> Brandt et al. Ann Rheum Dis. 2007. Hermann et al. Rheumatology. 2009. Poddubnyy et al. J Rheumatol. 2011. Braun et al. Ann Rheum Dis. 2011. Sieper et al. Ann Rheum Dis. 2013. Hamilton et al. Rheumatology 2013. Juanola et al. Reumatol Clin. 2013. Braun et al. Rheumatology 2013. van der Berg et al. Rheumatology 2013. van Hoeven et al. Arthritis Care Res. 2013. van Hoeven et al, EULAR 2013 Poster. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5177
Abstract 699: Uterine serous papillary carcinomas overexpress human trophoblast-cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Authors: Alessandro D. Santin, Emiliano Cocco, Joyce Varughese, Christine E. Richter, Francesca Casagrande, Stefania Bellone, Karim El-Sahwi, Marta Bellone, Paola Todeschini, Dan-Arin Silasi, Masoud Azodi, Peter E. Schwartz, Thomas J. Rutherford, Sergio Pecorelli
Journal: Cancer Research (2010)

Abstract Purpose: To evaluate the expression of human trophoblast cell-surface marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a novel therapeutic strategy against Uterine Serous Papillary Carcinoma (USPC), a biologically aggressive and chemotherapy resistant variant of endometrial cancer. Methods: Trop-2 expression was evaluated by real time-PCR and flow cytometry in six primary uterine serous papillary carcinoma cell lines recently characterized in our laboratory. Sensitivity to hRS7 antibody-dependent-cellular-cytotoxicity (ADCC) was tested in standard 5-hrs 51Cr release-assays against primary USPC cell lines expressing different levels of Trop-2. Finally, to investigate the effect of interleukin-2 (IL-2) on hRS7-mediated ADCC, 5-hrs 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU/ml). Results: Trop-2 mRNA transcript was significantly overexpressed in 3 out of 6 USPC primary cell lines when compared to normal human endometrial-cells (NEC) [p=0.005]. Consistent with RT-PCR data, high surface expression of Trop-2 was detected by flow cytometry in Trop-2 overexpressing cell lines [i.e., percentage of positive cells = 100% in all 3 positive cell lines, median (minimum-maximum) MFI (mean fluorescence intensity) of 184.2 (62.5-276.2)]. Importantly, while these USPC cell lines were found highly resistant to natural killer dependent cytotoxicity in the absence of the hRS7 antibody (range of killing 1.1% to 12.4%), they showed high sensitivity to hRS7-mediated ADCC in vitro (range of killing 28.2% to 64.4%) (P&amp;lt; 0.001). Incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity against USPC cell lines overexpressing Trop-2 (p= 0.01). Conclusion: Primary USPC cell lines may overexpress Trop-2 at mRNA and protein level and are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel, potentially highly effective therapeutic strategy in patients harbouring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 699.
AB0925 Enthesis ultrasound in patients with psoriatic sponylarthritis
Authors: A.-M.-M. Ramazan, C. Pana, M. Suta, L. Muflic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Spondylarthritis are entities that are pathogenetically distinct from rheumatoid arthritis and have some characteristically features like inflammation of bony insertion for tendons and ligaments (enthesopathy), which is considered a hallmark of the disease(1). McGonagle et al proposed that an enthesitis is the primary lesion in psoriatic arthritis and it might be a activity index of this disease (3). Enthesitis is best visualised by ultrasonography or MRI and is only detected on radiography after ossification process has occurred (4). <h3>Objectives</h3> to assess enthesitis in patients with psoriatic spondylarthritis comparing with a control group with ankylosing spondylitis. <h3>Methods</h3> We had included 29 patients with psoriatic spondylarthritis (with axial involvement) using CASPAR criteria followed in our rheumatology department between September 2011 and January 2012. The assessment included disease activity (pain score, patient global assessment, tender joints, swollen joint, BASDAI score, ESR, CRP), functionality assessment (BASFI score) and the ultrasound assessment of enthesitis (MASEI score) (5). The control group (22 patients) with ankylosing spondylitis, diagnosed by using NewYork criteria, were assessed on the same manner. <h3>Results</h3> All 51 eligible patients from two groups were evaluated. There were no significant differences in age mediana, biological therapy (20.7% in PA, 17.6% in AS group) but were in gender ratio (male of PA 58.6%, of AS 86.4%), DMARD-therapy(86.2% in PA, 41.2% in AS) or in familial history of psoriasis (17.2% in study group). There are no differences in MASEI score between groups (2.10±1.93, 1.91±2.52 respectivelly) in contrast to BASDAI (p=0.006), BASFI score (p=0.011) and to clinical variables (like tender joints, swollen joints). The MASEI score had correlated in all patients only with VAS (p=0.08, r=0.2), swollen joints (p=0.06, r=0.3) and CRP (p=0.03, r=0.3), but in psoriatic arthritis only with clinical variables, like VAS (0=0.05, r=0.3) and BASDAI score (p=0.08. r=0.3). <h3>Conclusions</h3> The enthesitis mirrors the activity of disease and influences the pain scores like VAS or BASDAI, but is not more present than in patients with ankylosing spondylitis. <h3>References</h3> Koopman WJ,Moreland WL, Arthritis and Allied Conditions, 2004, Lippincott Edition McGonagle et al, PA: a unified concept twenty years on; ArthritisRheum 1999; 42: 1080-86 Bijlsma JW et al., Eular Compendium of Rheumatic Diseases, 2009, BMJ Publishing Group De Miguel E et al, Diagnostic accuracy of enthesis ultrasound in the diagnosis of early spondyloarthritis, AnnRheumDis 2011, 70: 434-9 <h3>Disclosure of Interest</h3> None Declared
BONE AND SOFT TISSUE UPTAKE AND RETENTION FROM A THERAPEUTIC DOSE OF Sn-117m(4+)DTPA IN A PATIENT WITH METASTATIC BONE CANCER.
Authors: F. M. Swailem, G. T. Krishnamurthy, S. C. Srivastava, M. L. Aguirre, T. K. Walsh
Journal: Clinical Nuclear Medicine (1998)

s Presented At The 22Nd Annual Western Regional Meeting Of The Society Of Nuclear Medicine October 1997