tbuckley/cabot-search huggingface dataset:
Abstract 1936: Anti CD30 chimeric immune receptor mRNA for therapy of CD30+ lymphomas
Authors: Pavel Karkanitsa, Sherman Weissman, Peter Rabinovich, Hinrich Abken, Andreas Hombach, Marina Komarovskaya, Francine M. Foss
Journal: Cancer Research (2010)

Abstract CD30 is a transmembrane receptor which is overexpressed on Hodgkin lymphoma and large cell anaplastic lymphoma and represents an attractive target for therapy. Current methods of immunotherapy of CD30+ lymphomas include antibody based therapy (immunotoxins, bispecific molecules, radioimmunotherapy), and cellular immunotherapy. Here we describe an approach to cellular immunotherapy of CD30+ lymphomas using a synthetic mRNA of an anti CD30 chimeric immune receptor (anti CD30-CIR) introduced into activated T cells by electroporation. Anti-CD30 CIR consists of a single chain antibody directed against CD30, a transmembrane anchor to localize the protein in the cellular membrane, and the cytoplasmic domain of the TcR receptor chain. In these studies, the cDNA coding sequence was used as a template to produce anti CD30-CIR mRNA. Normal T cells expanded in vitro were electroporated with CIR mRNA and expression of anti CD30-CIR was detected by biotin-conjugated F(ab’)2 followed with Streptavidin-APC. To measure cytotoxicity of the CIR, target cells (HH, K562, Jurkat) were pulsed with carboxyfluorescein diacetate succinimidyl ester (CFSE) and then were cultured with T cells transfected with anti-CD30 CIR mRNA or mock transfected T cells. Cytotoxicity was evaluated at different target::effector (T: E) ratios and normalized by standard algorithm. Twenty-four hours after electroporation almost all viable T cell (&amp;gt;90%) expressed anti-CD30 CIR and were able to specifically kill CD30+ targets in a 4h in vitro assay. These results demonstrate that anti-CD30-CIR mRNA modified T cells can be generated and are capable of killing CD30-expressing cells in vitro and therefore may be an effective strategy for the therapy of refractory CD30-expressing lymphomas. 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 1936.
Recent Advances in Pulmonary Medicine
Authors: Steven E. Weinberger
Journal: New England Journal of Medicine (1993)

Traditionally a discipline based on physiology for the functional assessment of patients with lung disease, pulmonary medicine has been moving over the past decade into the realm of cellular and molecular biology in an attempt to unravel mechanisms of disease. Advances in understanding the pathogenesis of diseases such as cystic fibrosis, alpha1-antitrypsin deficiency, and asthma have resulted in changes in therapeutic strategy as well as new and promising forms of treatment. At the same time, more sophisticated imaging methods have opened up a new world of structural characterization of disease. On the other hand, the respiratory complications of . . .
Clues About Metastasis May Lead to Better Cancer Drugs
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Clues About Metastasis May Lead to Better Cancer Drugs Get access Jean McCann Jean McCann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Pages 636–638, https://doi.org/10.1093/jnci/87.9.636 Published: 03 May 1995
PWE-101 High definition endoscopy increases the number of adenomas detected in the UK bowel cancer screening population
Authors: P J Basford, S Tholoor, J Homer, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> Adenoma detection and removal is one of the main goals of colonoscopy. Improved adenoma detection has been shown to reduce future risk of colorectal cancer. High definition colonoscopy allows better visualisation of the colonic mucosa and may improve detection of polyps. Previous studies have shown variable results when comparing polyp and adenoma detection between standard definition (SD) and high definition (HD) colonoscopy. The UK bowel cancer screening programme offers colonoscopy to all citizens aged 60–75 years who test positive for faecal occult blood (FOB). We aimed to compare polyp and adenoma detection rates between those patients undergoing SD Colonoscopy and HD colonoscopy in the screening population. <h3>Methods</h3> Endoscopy, histopathology and screening database reports were analysed for all BCSP in our institution for the period September 2009 to October 2011. 1020 colonoscopies were performed of which 68 were excluded from further analysis (Incomplete procedure/polyposis syndrome/colitis/unknown definition of endoscope/previous colonic resection). Procedures were divided according to the definition of endoscope used: SD (500 000 pixels) n=421, HD (&gt;500 000 pixels) n=531. Reports were analysed for demographic data, bowel preparation, withdrawal time, and the number, size, morphology, site and histology of all lesions removed. <h3>Results</h3> There were no significant differences between the SD and HD groups respectively in percentage male subjects (57% vs 60.0%, p=0.229), mean age (66.47 vs 66.54, p=0.24), percentage with good or adequate bowel preparation (96.1% vs 96.2%, p&gt;0.5), mean withdrawal time (10.9 min vs 10.6 min, p=0.06). In total 1553 lesions were detected: 49 cancers, 1149 adenomas and 335 non-neoplastic polyps. There was no significant difference between the SD and HD in overall polyp detection rate (SD 0.63 vs HD 0.65, p=0.401) and adenoma detection rate (SD 0.59 vs HD 0.59, p=0.516). However a significantly greater number of adenomas per patient (APP) were detected in the HD group (SD 1.20 vs HD 1.34, p=0.016). HD endoscopy detected significantly more diminutive adenomas (1–5 mm) than SD endoscopy (0.87 per pt vs 0.72 per pt, p=0.02), but there was no difference in the rate of detection adenomas &gt;5 mm. More adenomas were detected in the proximal colon in the HD group (0.59 vs 0.44, p=0.03) but there was no significant difference in the distal colon (HD 0.79 vs SD 0.77). <h3>Conclusion</h3> Overall adenoma detection rate in this study population was excellent with 59% of patients having one or more adenomas detected. HD endoscopy appears to improve the total number of adenomas detected in the screening population. The main gain of HD endoscopy is in detection of diminutive polyps in the proximal colon. <h3>Competing interests</h3> None declared.
S1 High Levels of Latent TB Infection, Blood Borne Viruses and Unmet Need Among Hard to Reach Groups in London: The TB Reach Study
Authors: S Yates, S Hemming, L Possas, G Fernando, V Gant, E Garber, AM Geretti, J Harvey, A Hayward, M Lipman, T McHugh, J Watson, A Story
Journal: Thorax (2012)

<h3>Background</h3> Urban homeless people have high levels of disease and often present late for healthcare. Despite high rates of active TB in London’s large homeless population, limited data are available regarding the prevalence of latent TB infection (LTBI) and blood borne viruses (BBV) - HIV, Hepatitis B &amp; C. We have undertaken a TB/BBV screening programme to assess the prevalence of LTBI, infection with BBV and co-infection within hard to reach groups (homeless people and substance misusers) in homeless hostels and residential drug services in London. <h3>Method</h3> Residents screened for TB on a mobile chest x-ray unit were approached and with consent, blood was drawn for TB IGRA (Quantiferon In-Tube) and BBV. Results were fed back to participants with onward referral as necessary. <h3>Results</h3> Of 413 eligible participants, 390 (94%) reported a history of homelessness. Of these 390 participants, 89% were male, 68% were 16–49 years of age and 66% UK born. 17% were IGRA positive, 1% HIV positive (all previously known), and 10% had current and 4% past Hepatitis C. 1% of those screened had current Hepatitis B infection, 10% past infection, 18% had vaccine induced protective levels of immunity and 71% had insufficient or no Hepatitis B immunity. 29% of subjects with Hepatitis C were LTBI co-infected. Multivariate analysis identified increasing age e.g. 30–49 age group (odd ratio [OR], 2.15; 95% confidence interval [CI95], 0.84–5.49) compared to the under 30, foreign birth (OR, 6.59; CI95, 3.50–12.39), smoking hard drugs (OR, 2.19; CI95, 1.02–4.64), and injecting hard drug (OR, 2.36; CI95, 1.08–5.16) such as heroin, crack or cocaine (although 95% of injectors also smoked hard drugs) as risk factors for LTBI. Injecting drug use was the only factor associated with increased risk for Hepatitis C infection (OR, 19.62; CI95, 8.23–46). <h3>Conclusion</h3> Extremely high rates of LTBI, Hepatitis C and co-infection are present in our urban study population. Despite targeted Hepatitis B vaccination programmes, a high proportion of participants appear unvaccinated. These levels of unmet need have major implications for public and personal healthcare planning and should be recognised through appropriate targeted health and social policy.
AB0048 The role of adiponectin in the production of il-6, il-8, vegf, and mmps in human endothelial cells and osteoblasts: implications for arthritic joints
Authors: K.-S. Kim, Y.-A. Lee, K.-Y. Kim, S.-S. Kim, S. Hong, R. Song, H.-I. Yang
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The role of adiponectin in the pathogenesis of rheumatoid arthritis was previously studied in relation to the production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLS). <h3>Objectives</h3> This study was performed to evaluate the contribution of adiponectin to the production of IL-6, IL-8, VEGF, MMP-1, and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. <h3>Methods</h3> Cultured human umbilical vascular endothelial cells (HUVEC) and osteoblasts were stimulated with adiponectin (1 or 10 μg/ml) or IL-1β (0.1 ng/ml) in the presence or absence of hypoxia for 24 hrs. The gene expression patterns of culture supernatants and cells were analyzed by ELISA and PCR, respectively. <h3>Results</h3> Adiponectin significantly stimulated the expression of VEGF, MMP-1, and MMP-13 in osteoblasts but not in HUVEC, while it significantly stimulated the expression of IL-6 and IL-8 in both HUVEC and osteoblasts. The increase of VEGF expression by adiponectin was significantly higher than that by IL-1β stimulation. The expression of IL-6 and IL-8 in adiponectin-stimulated HUVEC was about 10-fold higher than that of IL-1β, but about 2-fold higher in osteoblasts. In addition, IL-8 expression levels in HUVEC were about 7-fold higher than that of osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may play an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases observed in gene expression by adiponectin were differentially regulated by hypoxia. <h3>Conclusions</h3> Adiponectin plays a more important role in the production of mediators driving synovitis and joint destruction in endothelial cells and osteoblasts than that of IL-1β at physiological concentrations. <h3>References</h3> <i>Arthritis Res Ther</i> 2009, <b>11</b>(6):R161 <h3>Acknowledgements</h3> Basic Science Research Program through the National Research Foundation of Korea (NRF) (grant numbers 2010-0024089 and 2011-0009061) <h3>Disclosure of Interest</h3> None Declared
BM-28 * BIOLOGICAL PATHWAYS ASSOCIATED WITH BREAST CANCER METASTASIS TO THE BRAIN
Authors: L. Rogers, V. Varadan, A. Palkar, K. Miskimen, N. Williams, M. Morton, S. Maximuk, S. Vinayak, A. Sloan, J. Barnholtz-Sloan, H. Gilmore, L. Harris
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain metastases (BM) from breast cancer are associated with poor prognosis. While basal-like and HER2+ cancers are at highest risk of BM, no effective treatments exist. Comprehensive characterization of the transcriptome of matched primary breast (PB) tumors and BM may allow for discovery of pathways mediating BM. METHODS: Pathology records were searched for surgical resection of BM from PB. Archival FFPE material was obtained along with chart and tumor registry clinical data. TMA sections were stained with ER, PR and HER2. Tumor DNA/RNA was extracted from macrodissected 2 mm cores from FFPE. Gene expression profiling was performed using Affymetrix HTA 2.0 arrays on 96 FFPE samples for whom sufficient RNA was available. PAM50 subtypes were derived and differential gene expression between BM and PB was estimated using the Mann-Whitney-Wilcoxon test followed by multiple testing correction. Pathway enrichment analysis was performed using KEGG and NCI Pathway Interaction Databases. RESULTS: 68 BM were identified. 30 had matching PB tissue. BMs were predominantly parenchymal (dural-based, 11). Most were supratentorial. We found a total of 390 genes to be significantly differentially expressed (pval < 0.05; FDR < 0.1) between the 27 matched brain mets and primary tumor pairs. Persistent enrichment of integrins and immune-related pathways were seen among the modulated genes. Also, STAT3 activation in brain mets compared to primary tumors may suggest the possibility of Jak or IL-6/IL-6R interactions as potential therapeutic targets. CONCLUSIONS: Our study shows significant modulation of driver pathways in BM when compared with matched PB tumors.
331 CO-STIMULATION VIA CD27 MIGHT IMPORTANTLY CONTRIBUTE TO ANTI-HCV ACTIVITY OF NK CELLS
Authors: M. Eisenhardt, A. Gl ässner, P. Kokordelis, B. Krämer, F. Wolter, C. Boesecke, J.K. Rockstroh, C.P. Strassburg, U. Spengler, J. Nattermann
Journal: Journal of Hepatology (2013)
AB0747 Churg-strauss syndrome complicated by heart inflammatory pseudotumor
Authors: D. Cammelli, M. Rosselli
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Churg-Strauss syndrome is a systemic necrotizing vasculitis of small and medium vessels of unknown etiology associated to asthma and characterized by peripheral eosinophilia, extravascular granulomatous inflammation with eosinphilic infiltrates that may be associated to ANCA. Heart involvement has been reported in about 50% of cases and is considered one of the most feared complications<sup>1</sup>. <h3>Objectives</h3> A 56-years-old woman with a past medical history of poorly controlled bronchial asthma, was admitted to hospital complaining of shortness of breath, dry cough and lower extremities pitting edema developed over the last two months. Her background history in the presence of peripheral eosinophilia, multiple lung infiltrates on xray and high resolution computed tomography, mononeuritis multiplex and ANCA positivity established the diagnosis of Churg-Strauss syndrome. Echocardiography revealed an anterior pericardial effusion and a pericardial mass of 3 x 5 cm completely attached to the right ventricular wall. These features were confirmed by a trans esophageal approach and subsequently by a heart MRI that defined the presence of a large cardiac mass indistinguishable from the right atrium and ventricular wall, invading the atrioventricular sulcus and incasing the origin and the proximal tract of the right coronary artery. Biopsy ruled out a cardiac tumor showing features of granulomatous inflammation with diffuse eosinophilic infiltration and no cellular atypia. The patient was treated with boluses of cyclophosphamide and high doses of methylprednisolone with prompt clinical improvement and complete resolution of the cardiac mass as shown by clinical- radiological follow up. <h3>Conclusions</h3> The patient presented features resembling right heart impairment secondary to a large inflammatory pseudotumor associated to Churg-Strauss syndrome. MRI is the gold standard to define cardiac constriction syndromes and Churg-Strauss heart involvement<sup>2,3</sup>. Cyclophosphamide and corticosteroids represent the cornerstone of treatment with remarkable response even in advanced cases if promptly administered<sup>1</sup>. <h3>References</h3> Chiara Baldini, MD, PH, Rosaria Talarico, MD, PHD, Alessandra Della Rossa MD, PHD, Stefano Bombardieri, MD. Clinical Manifestations and Treatment of Churg Strauss Syndrome. Rheum Dis Clin N Am 36 (2010) 527–543 Rory O'Hanlon, MRCPIa, DudleyJ. Pennell, MD, FRCP, FACCa,b,*. Cardiovascular Magnetic Resonance in the Evaluation of Hypertrophic and Infiltrative Cardiomyopathies. Heart Failure Clin 5 (2009) 369–387 J.P. Smedema, P. van Paassen, et al. Cardiac involvement of Churg Strauss syndrome demonstrated by magnetic resonance imaging. Clin Exp Rheumatol 2004; 22 (Suppl. 36): S75-S78. <h3>Disclosure of Interest</h3> None Declared
RANDOMIZED TRIAL OF INTRACORONARY ERYTHROPOIETIN THERAPY AT THE TIME OF REPERFUSION IN ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Won-Woo Seo, Jung-Won Suh, Jin-Joo Park, Chang-Hwan Yoon, Young-Seok Cho, Tae-Jin Youn, In-Ho Chae, Dong-Ju Choi
Journal: Journal of the American College of Cardiology (2015)
THU0448 The Profile of Musculoskeletal Ultrasonography in Patients with Adult Onset Still Disease.
Authors: A. Ihata, D. Kishimoto, T. Uehara, M. Hama, R. Yoshimi, A. Ueda, M. Takeno, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adult onset Still disease (AoSD) is a systemic inflammatory disease and characterized by daily spiking high fevers accompanied by a rash, arthritis, and systemic manifestations. The clinical course of AoSD can be divided into three patterns; monophasic pattern, polycyclic pattern, and chronic articular pattern. Especially in chronic articular pattern, patients may have severe, destructive arthritis. Although chronic articular pattern was mimicking RA, there was a few reports that mentioned about the finding of musculoskeletal ultrasonography of AoSD. <h3>Objectives</h3> To examine the profile of musculoskeletal ultrasonography (MSUS) in patients with AoSD. <h3>Methods</h3> Twenty-seven cases of 20 patients with AoSD were enrolled, who consulted to our department between 2003 and 2012. Laboratory data, physical findings, and medication were collected. Using MSUS, semi-quantitative evaluation by gray scale and power Doppler were performed. <h3>Results</h3> There are 35 patients with adult onset Still disease in our department (10 male and 25 female). Median age of onset was 49.5. The proportion of clinical course was as about as follows; monophasic 22.2%, polycyclic 55.6%, and chronic articular 22.2%, respectively. On the background of MSUS, 10 cases were male and 17 cases were female. The onset age was 57.5 years old (median). The positive rate of CRP, ferritin, and LDH was 81.0%, 93.3%, and 29.4%, respectively. In MSUS, the positive rate of GS was 34.8% in MCP, 26.2% in PIP, 50.0% in hand, and 20.7% in knee joints respectively. The positive rate of PD was 19.0%, 5.8%, 42.6%, and 22.4%, respectively. The average of GS score was 1.1±0.1, 0.8±0.1, 1.3±0.2 and 0.7±0.1, respectively. The average of PD score was 0.5±0.1, 0.2±0.1, 1.1±0.1, and 0.1±0.1, respectively. Coefficient of correlation between ferritin and GS score of hand joints was higher than other joints (0.424). Correlation between ferritin and PD score of hand joint was also higher than other joints. <h3>Image/graph</h3> <h3>Conclusions</h3> The positive rate of GS was higher than PD in patients with adult onset Still disease. GS and PD signals were frequently observed in hand joints and were correlated with the level of ferritin. <h3>Disclosure of Interest</h3> None Declared
A Case of Creutzfeldt-Jakob Disease Mimicking Corticobasal Degeneration
Authors: Yuyang Zhang, Satoshi Minoshima, Hubert Vesselle, David H. Lewis
Journal: Clinical Nuclear Medicine (2012)

A 58-year-old woman was admitted with left-sided decreased sensation, ataxia, and left "alien" hand and leg. Brain SPECT and PET showed hypoperfusion and hypometabolism in the right frontoparietal cortices, including the primary sensorimotor cortex, and temporal cortex. MRI demonstrated matching-restricted diffusion and fluid-attenuated inversion recovery hyperintensity. Corticobasal degeneration was suspected initially. The patient declined rapidly, and the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) was made based on cerebrospinal fluid biomarkers. CJD can present with symptoms similar to other disorders. This case illustrates that CJD can mimic a rare neurodegenerative disorder, cortico-basal degeneration, both clinically and by neuroimaging.
Abstract 55: Glucose metabolism influences migration of high-grade glioma in vitro by modification of TGF-beta2
Authors: Petra Leukel, Corinna Seliger, Arabel Vollmann, Anett Doerfelt, Ulrich Bogdahn, Peter Hau
Journal: Cancer Research (2010)

Abstract Introduction: Lactate dehydrogenase type A (LDH-A) is a key metabolic enzyme catalyzing pyruvate into lactate and is excessively expressed in several human tumors. Transforming growth factor-beta2 (TGF-beta2) is a key regulator of invasion in high-grade gliomas, partially remodeling the extracellular matrix (ECM) and inducing proteinases. Thrombospondin1 (THBS-1) is an extracellular protein important for activation and processing of TGF-beta2. A microarray of LDH-A knocked-down glioma cell RNA showed down regulation of THBS-1 and TGF-beta2. In this study, we tested the hypothesis that LDH-A influences TGF-beta2 activation by up regulation of THBS-1 leading to an enhanced migration of high-grade glioma in vitro. Methods: We performed LDH-A knock-down by transient transfection of glioma cells with small interfering RNA directed against LDH-A (siLDH-A). Expression levels of TGF-beta2 and THBS-1 in siLDH-A transfected cells were investigated using microarrays, RT-PCR, Western Blot and ELISA. Migration of transfected cells was investigated by Boyden Chamber and scratch assays. Results: siLDH-A suppresses TGF-beta2 in high-grade glioma and decreases the expression of THBS-1 on the RNA and protein level. THBS-1 leads to an increased level of activated TGF-beta2 in supernatants of siLDH-A treated cells. In migration assays, siLDH-A leads to a decreased migration of high-grade glioma cells. Discussion: We demonstrate, for the first time, that knockdown of LDH-A can decrease the RNA and protein level of TSP-1 and consecutively the processing of TGF-beta2. Additionally, knockdown of LDH-A decreases the RNA level of TGF-beta2. Both results may contribute to an enhanced level of TGF-beta2 and increased migration, given that LDH-A is expressed. An increased expression of LDH-A has been found in aerobic glycolysis, a mechanism well known from several human cancers. Recent paper showed that LDH-A is able to bind RNA. Thus we suppose LDH-A could influence the level of TGF-beta2 RNA by RNA stabilization. Together with our recent results that show that TGF-beta enhances migration in high-grade gliomas, we demonstrate a new panel of interactions between lactate metabolism and TGF-beta2 that might be crucial for glioma migration and possibly invasion. 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 55.
Holding on to Humanity
Authors: K. Collins
Journal: BMJ (2012)

When Shamai Davidson (1926-1986) began his groundbreaking work towards understanding the psychological traumas of holocaust survivors in Israel in 1955 he was appalled by the silence and seeming indifference of his psychiatric colleagues. Davidson was born in Dublin but grew up in Scotland, completing his medical studies at the University of Glasgow in 1950. Though living in the security of wartime Glasgow he was acutely aware of the fate of European Jewry and in particular that of his father’s two sisters and all their children, who were to perish at the Treblinka death camp in Nazi occupied …