tbuckley/cabot-search huggingface dataset:
A1.25 Visualisation and characterisation of citrullinated antigen-specific B cells from peripheral blood of patients with rheumatoid arthritis
Authors: PF Kerkman, E Fabre, EH van der Voort, KL Germar, DL Baeten, TWJ Huizinga, REM Toes, HU Scherer
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> In Rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) represent highly disease-specific biomarkers found in the majority of patients. As ACPA have been implicated in disease pathogenesis, it is of crucial relevance to understand the underlying B cell response. In this context, visualisation of citrullinated antigen-specific B cells would allow for a detailed characterisation of the immune response to better understand its development and maintenance. Unfortunately, visualisation of autoreactive B cells in humans has proven extremely difficult. <h3>Materials and methods</h3> Using the CCP2-antigen and its arginine control variant, we developed a multicolour tetramer-based staining method to visualise citrullinated antigen-specific B cells in peripheral blood of RA patients by flow-cytometry. Specificity of the staining was verified by culturing tetramer-positive and -negative B cells isolated by FACS. Citrullinated antigen-reactive B cells were further phenotyped using cell surface markers associated with developmental and functional B cell characteristics. Finally, the frequency of citrullinated antigen-reactive B cells was correlated to ACPA serum levels and <i>in vitro</i> ACPA production. <h3>Results</h3> The staining procedure successfully separated citrullinated antigen-reactive B cells from non-specific background signals. Already fourteen FACS-sorted tetramer-positive B cells produced detectable amounts of ACPA, whereas no ACPA production was observed in cultures of up to 5000 tetramer-negative B cells. The majority of citrullinated antigen-reactive B cells had a post-germinal centre memory or plasmablast phenotype. Up to 1 in 200 memory B cells were directed against citrullinated antigens, and their frequency correlated with spontaneous ACPA production in culture and ACPA serum titres <i>in vivo</i>. <h3>Conclusions</h3> We show, for the first time, the specific and reliable identification of citrullinated antigen-specific B cells in high frequencies in peripheral blood of RA patients. The majority of this population has a memory phenotype and closely reflects the dynamics of the <i>in vivo</i> ACPA response. These data provide the basis for a detailed characterisation of this disease-specific immune response on a single cell level and could lead to the identification of novel therapeutic targets.
Abstract P5-15-04: A Randomized Trial Comparing Intermittent Pneumatic Compression with Manual Lymphatic Drainage for Treatment of Lymphedema in Patients with Breast Cancer
Authors: S Ozkan Gurdal, A Kostanoglu, I Cavdar, A Ozbas, N Cabioglu, B Ozcinar, M Muslumanoglu, A Igci, V. Ozmen
Journal: Cancer Research (2010)

Abstract Aim: Lymphedema is a serious complication associated with axillary surgery and/or radiotherapy in patients with breast cancer. The aim of this randomized study was to assess the efficacy of two different treatment modalities of lymphedema by comparing the manual lymphatic drainage and compression bandage with intermittent pneumatic compression and self-lymphatic drainage. Material and Methods: Thirty patients diagnosed with lymphedema after treatment for breast cancer were randomized to either manual lymphatic drainage (MLD)by physicotherapists with compression bandage-group (n=15) or to the intermittent pneumatic compression (IPC)-group with self-lymphatic drainage massage (n=15). In both groups, treatment program was performed three days a week, every other day for 6 weeks. To determine the efficacy of the treatment modalities, arm circumferences were measured from wrist to shoulder girdle with 10 cm distance before and after treatment for lymphedema at the 1st, 3rd, and 6th weeks of the therapies. Tests evaluating the quality of life including EORTC-QLQ and ASES-test were also performed before and after treatment at 6th week. Results: The median age of patients was 54.5 years (31-74) and lymphedema occured after a median time of 18 months following surgery (range, 6-72 months). Patients in both groups had similar demographic and clinical characteristics. At the 6th week, even though both treatment modalities resulted in significant decreases (p&amp;lt; 0.001) in the total arm volume (12.2% decrease in IPC-group versus 14.9% decrease in MLD-group), no significant difference could be found in the therapeutic efficacy between the IPC-and MLD-groups. Furthermore, significant improvements of ASES scores were detected after both IPC-and MLD-therapies (p=0.001), but there was no statistically significance between two groups. In the EORTC-QLQ-C30 quality of life test, however, global health status, functional and cognitive functioning scores appeared to be improved only after MLD-therapy, whereas emotional functioning scores, fatique and pain scores significantly improved after MLD-or IPC-therapy. Conclusion: Both treatment modalities by MLD and IPC appear to be effective in the treatment of lymphedema with similar therapeutic efficacy in patients with breast cancer. MLD-therapy seems to be superior to IPC-therapy since there is a trend of an improvement in the quality of life in patients treated with MLD. However, IPC might still be the preferred treatment for some patients who work at the day time since it could be performed easily at home by themselves without a need for a physicotherapist at the hospital. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-15-04.
Abstract 2167: Unbiased genomic approaches identify 2 major subclasses of Gastric Cancer with prognostic and predictive value superior to Lauren's and also reveals subtype-specific treatment opportunities
Authors: Iain B. Tan, Julian Lee, ChiaHuey Ooi, MingHui Lee, Alex Boussioutas, Manuel S. Tallez, Joanne Ngeow, KiatHon Lim, Jimmy So, SuPin Choo, WaiKeong Wong, Patrick Tan
Journal: Cancer Research (2010)

Abstract Introduction: The Lauren's classification of gastric cancer (GC) is widely used with 2 subtypes, intestinal and diffuses having distinct histo-pathological and epidemiological characteristics. Beyond diagnosis, Lauren's classes have limited prognostic and no predictive value. Methods: We performed gene expression profiling on 37 GC cell lines (GCCL) and 2 independent cohorts of 200 (SG) and 68 (AU) primary GC tumors. We used integrative molecular profiling to discover and characterise molecular subtypes of GC. Results: Unsupervised hierarchal clustering in GCCLs identified 2 distinct major molecular subtypes termed “G1”and “G2”. Linear models for microarray data (LIMMA) identified 171 distinguishing genes. These were mapped into 2 independent datasets of primary tumors where G1 and G2 subclasses were again identified. G1/G2 subtypes, discovered by unbiased techniques, were found to be related to intestinal and diffuse histology respectively (p &amp;lt; 0.001, chi square test) with 69% concordance. We found G1/G2 but not Lauren's classes to be prognostic (G1 vs G2: median survival: 41 vs 25 mths, HR 1.5, 95% CI: 1.1-2.0 p=0.02; Laurens: p=0.6). Among discordant cases, survival approximated G1/G2 classes rather than Laurens. Survival was superior in “G1 but diffuse” compared to “G2 but intestinal” (median 36 vs 17 months, p=0.08). We next examined the interaction of the subclasses with 5-fluorouracil (5-FU), the only chemotherapy approved for adjuvant treatment of GC. 5 -FU sensitivity as measured by GI-50 in a previous publication was greater in G1 lines (p=0.04). In primary tumours, G1 patients had improved progression free survival with 5FU/RT of borderline significance (test for interaction, p=0.09). We next applied genomic pathway analysis using an approach we previously published (Ooi et al. Plos Genetics 2009). Her2/Ras/ER/PR/BRCA pathways and VEGF/p53/EGFR pathways were deregulated in G1 and G2 subtype respectively suggesting possible subtype specific treatment opportunities. Conclusion: We describe an unbiased genomic approach that improves upon Lauren's to identify the two major subclasses of gastric cancer. G1/G2 classes have superior prognostic and predictive value and subclass specific therapeutic opportunities. 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 2167.
Endoscopic ultrasound-guided celiac plexus neurolysis and direct celiac ganglia neurolysis for pancreatobiliary cancer pain
Authors: Iwata Keisuke
Journal: Endoscopy (2011)

Background: Advanced panctobiliary cancer is frequently associated with severe upper abdominal pain and back pain. Narcotic analgesics are usually effective in relieving such cancer pain, but they induce adverse effects, such as constipation, nausea, vomiting, drowsiness, and delirium, in some patients. In such patients, celiac plexus neurolysis (CPN) can act a good alternative for reducing the pain. This technique was originally performed as an open surgery or under radiographic guidance. Nowadays, real-time imaging guidance in the form of ultrasound guidance has made CPN much safer and easier. However, this new technique, endoscopic ultrasound-guided CPN (EUS-CPN), is not always efficacious, and a limited number of patients are known to benefit from it. The main reason this technique has limited efficacy was that the celiac ganglia (CG) cannot be imaged. However, CG can now be visualized by EUS; therefore, direct injection into individual CG and direct CG neurolysis (CGN) are possible.
Abstract 539: The expression of monocyte/macrophage-restricted scavenger receptor CD163 by malignant cells may be a consequence of cell fusion with tumor-associated macrophages: A novel target for cancer therapy
Authors: Maciej B. Maniecki, William E. Damsky, Benedicte P. Ulhøi, Torben Steiniche, Torben F. Ørntoft, Lars Dyrskjøt, Michael Borre, Eigil Kjeldsen, Marcus W. Bosenberg, Holger J. Møller
Journal: Cancer Research (2011)

Abstract Solid tumors contain large a number of infiltrating macrophages, which are believed to play a key role in progression and metastasis. Recent research has indicated that malignant cells at times express molecular pathways normally only observed in myeloid cells such as macrophages, hence suggesting that macrophages may fuse with tumor cells. In the present work, we aimed to investigate tumor cell expression of the monocyte/macrophage-restricted scavenger receptor CD163. Initially, the tumor expression of CD163 was examined using a bladder cancer tissue microarray (TMA) containing 425 cores of tumor tissue from 425 patients and 43 paired metastatic lymph nodes. Tumor cells showed a characteristic pleomorphic and atypical morphology with large nuclei, and they were easily distinguished from macrophages. Immunohistochemical staining revealed that CD163-expressing tumor cells could be detected in 98% of the tumor cores, and CD163-expressing metastatic cells could be identified in 77% of the cores of lymph node biopsies. Quantitative real-time polymerase chain reaction and flow cytometric analysis showed that bladder cancer cell lines did not express CD163; however, when co-cultured with macrophages a significant induction of CD163 expression was observed. Utilizing the xCELLigence Real-Time Cell Analyzer System we showed that macrophage-tumor hybrid cells exhibited a significantly increased migratory capacity compared to non-hybrid tumor cells. Tracing the Y chromosome in co-cultures of male macrophages and female T24 cells, we found T24 cell nuclei to be fused with the macrophages. A Cre-inducible mouse model of melanoma expressing a fluorescent reporter system (GFP) was used to characterize hybrid cell formation of macrophages with GFP positive tumors cells in vivo. Flow cytometric analysis demonstrated that &amp;gt;90% of the murine GFP positive tumor cells co-expressed CD163. In conclusion, we show that the expression of the monocyte/macrophage scavenger receptor CD163 was not confined to tumor-associated macrophages. In fact, a significant portion of the tumor cells also expressed CD163, possibly as a result of heterotypic cell fusion between tumor cells and macrophages. Our findings identify CD163 as a possible target for novel cancer therapy. 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 539. doi:10.1158/1538-7445.AM2011-539
AN ANOMALOUS LEFT CORONARY ARTERY BRANCHING OFF THE PULMONARY ARTERY (BLAND-WHITE-GARLAND SYNDROME) DIAGNOSED BY 320 DETECTOR ROWS COMPUTED TOMOGRAPHY
Authors: Keishi Ishikawa, Nobusada Funabashi, Koya Ozawa, Hiroyuki Takaoka, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2015)
576 ORAL ADMINISTRATION OF B. INFANTIS FAVOURS A REDUCTION IN MESENTERIC LYMPH NODE BACTERIAL DNA TRANSLOCATION EPISODES IN MICE WITH CARBON TETRACHLORIDE-INDUCED CIRRHOSIS
Authors: I. Gómez-Hurtado, P. Zapater, G. Peiró, J.M. González-Navajas, M. Pérez-Mateo, J. Such, Y. Sanz, R. Francés
Journal: Journal of Hepatology (2012)
OP0296 Hepatic Complication in Autoimmune Rheumatic Diseases: A Nationwide Cohort Study in Taiwan
Authors: C. H. Tung, N.-S. Lai
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The association between rheumatic diseases, liver cirrhosis and liver cancer has rarely been explored in Asian populations, an endemic area of viral hepatitis. <h3>Objectives</h3> The aim of this study was to investigate the relative risk of liver cirrhosis and liver cancer in Taiwanese patients with diverse rheumatic diseases and to identify groups of patients with a high risk. <h3>Methods</h3> We conducted a nationwide cohort study of the risk of liver cirrhosis and liver cancer in different rheumatic diseases among 29856 patients who had no history of malignancies, using the National Health Insurance database of Taiwan from 2005 to 2009. Hazzard ratios (HRs) of liver cirrhosis and liver cancer for various rheumatic diseases were analyzed. <h3>Results</h3> Among the patients with rheumatic diseases, 1987 liver cirrhosis and 1225 liver cancers were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95% CI 1.25-2.81). Patients with Sjogren' s syndrome (HR 1.04, 95% CI 0.62-1.75) and systemic sclerosis (HR 1.33, 95% CI 0.33-5.35) also had relative higher risk of liver cirrhosis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95% CI 0.19-0.44). Among rheumatic diseases patients, the patients with systemic sclerosis (HR 6.01, 95% CI 1.5-24.07), psoriasis (HR 1.74, 95% CI 1.06-2.85) and Sjogren's syndrome (HR 1.76, 95% CI 1.01-3.06) had significantly increased risk of liver cancer and the patients with Rheumatoid arthritis (HR 0.24, 95% CI 0.14-0.39) and systemic lupus erythematosus (HR 0.14, 95% CI 0.12-0.99) had decreased risk. <h3>Conclusions</h3> Patients with psoriasis, systemic sclerosis and Sjogren's syndrome have an increased risk of liver cirrhosis and liver cancer. Traditional DMARDs administration should be careful to avoid adverse effect of chronic liver fibrosis. Healthy lifestyle, avoidance of smoking and alcohol consumption, anti-viral treatment for co-existing viral hepatitis and regular monitoring of liver condition should be recommended in any rheumatic patients with high risks. <h3>Disclosure of Interest</h3> None Declared
Public Health in the Precision-Medicine Era
Authors: Ronald Bayer, Sandro Galea
Journal: New England Journal of Medicine (2015)

Interview with Dr. Ronald Bayer on why the heightened focus on precision medicine misses the point when it comes to public health. (10:54)Download The burgeoning precision-medicine agenda focuses on detecting and curing disease at the individual level, but there are multiple contributors to the production of population health, and clinical intervention cannot remedy health inequities.
Abstract 1556: Adipose tissue upregulates MMP9 expression in oesophageal cancer promoting invasion and migration <i>in vitro</i> and correlates with obesity status and poor differentiation <i>in vivo</i>
Authors: Graham Philip Pidgeon, Emma Allott, Claire Donohoe, MaryClare Cathcart, Sarah McGarrigle, Robert Cummins, Elaine Kay, John Reynolds
Journal: Cancer Research (2011)

Abstract Introduction: Obesity is an independent risk-factor for oesophageal adenocarcinoma. Adipose tissue is an endocrine organ secreting numerous factors with different biological activities. We aimed to investigate the molecular mechanisms linking obesity and cancer in oesophageal cancer. Methods: Adipose conditioned media (ACM) was prepared from omental adipose tissue of oesophageal adenocarcinoma patients. Proliferation of oesophageal adenocarcinoma cells(OE33, OE19) in response to ACM was examined by BrdU. OE33 cell line was co-culture with visceral adipose tissue and gene expression pathways assessed by Cancer-Pathway-Finder and Affymetrix arrays. Identified genes were assessed in 50 resected oesophageal tumours and related to clinic-pathological data. Migration and invasion following culture with ACM was assessed in oesophageal cell lines. Results: Culture of both the OE33 and OE19 cell lines with ACM from omental adipose tissue increased proliferation by 142% and 145% respectively. Co-culture of OE33 with adipose tissue increased the expression of genes regulating invasion and metastasis between 10-5000 fold, with MMP9 the most upregulated gene and TP53 down-regulated 2-fold. Altered genes were validated in an independent cohort. Functionally, co-culture of adipose tissue with tumour cells increased both mingration and invasion of tumour cells. Notably, adipose tissue from viscerally obese patients had a significantly higher effect. Markers of focal adhesions(SPP1, integrins), endothelial mesenchymal transition(SNAI2, Laminins) and thrombosis (pai-1) were also significantly upregulated. Expression of pai-1 and MMP9 was significantly (p&amp;lt;0.05) higher in tumours from centrally obese patients. Conclusion: Omental adipose tissue promoted oesophageal cancer aggressiveness by increasing proliferative, migratory and invasive capacity via upregulation of MMP2, MMP9, SERPINE1, PAI-1, SPP1 and SNAI2. Upregulation of genes in tumours from obese patients suggest a molecular progression of cancer associated with excess adipose tissue. 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 1556. doi:10.1158/1538-7445.AM2011-1556
PTU-226 Colorectal cancer screening in a moderate risk population; what is the polyp yield and what is the optimum screening interval?
Authors: M Walshe, R Moran, V Swan, J Trickovic, B Kelleher, P MacMathuna
Journal: Gut (2012)

Introduction Colorectal cancer (CRC) screening has been shown to reduce mortality from CRC. Many people with a family history of CRC do not satisfy criteria for syndromes such as HNPCC, and fall into a “moderate risk” category. The reported polyp burden in this group is varied, and the optimum screening regimen is controversial. Our aims were (1) to evaluate the polyp yield at screening colonoscopy in a “moderate risk” group (above average, non-HNPCC) in the setting of a family-screening clinic, (2) to compare polyp yield on 2nd screening colonoscopy between patients with and without adenomas on 1st screening colonoscopy, (3) to evaluate the potential for longer screening intervals for patients with no adenomas on 1st screening colonoscopy. Methods Family cancer history questionnaires were used to generate family pedigrees and identify “moderate risk” individuals using defined criteria. Adenoma yield on initial colonoscopy was evaluated, and comparisons were made between males & females, and subjects older & younger than 50 yrs. Advanced adenomas (AA) were defined as adenomas ≥10 mm, with high-grade dysplasia, or with a villous component. In patients who had >1 colonoscopy, adenoma yield on 2nd colonoscopy was compared between patients with and without adenomas on initial colonoscopy. Results From a cohort of 2008 individuals in a high-risk family-screening clinic, 971 (48%) have been assigned a “moderate risk” category. Complete data were available for screening colonoscopies in 236 of these; 99 male, 137 female. On initial screening colonoscopy, 17/236 (7%) had AA, and a further 37/236 (16%) had simple adenomas (SA), (total polyp yield 23%). Polyp yield was higher in males (8% AA, 18% SA) vs females (7% AA, 14% SA), and in the >50 yrs (13% AA, 20% SA) vs <50 yrs (3% AA, 13% SA). More than 1 screening colonoscopy was carried out in 127/236 (54%). Of the 30/127 (24%) who had an adenoma on initial colonoscopy, 4/30 (13%) had AA, and a further 7/30 (23%) had SA on 2nd colonoscopy (mean interval to f/u 3.62 yrs). In the cohort without adenomas at initial screening; 97/127 (76%), only 1/97 (1%) had an AA, and 10/97 (10%) had SA on 2nd colonoscopy (mean interval 4.6 yrs). Conclusion In this moderate risk group the polyp yield is highest in males, and those >50 yrs. Adenoma at initial colonoscopy was predictive of adenoma detection at 2nd colonosocopy. In contrast, for individuals without adenomas at initial screening, a very low adenoma yield was observed at follow-up screening. Consequently, within this “moderate risk” cohort, the data supports the adoption of differing screening protocols depending on age, gender, and adenoma yield on initial colonoscopy. Competing interests None declared.
ACUTE RECOIL FOLLOWING IMPLANTATION OF EVEROLIMUS-ELUTING ABSORB BIODEGRADABLE VASCULAR SCAFFOLDS OR XIENCE METALLIC STENTS: THE ABSORB II TRIAL
Authors: Bernard Chevalier, Yuki Ishibashi, Yoshinobu Onuma, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2015)
Study designs to compare new colonoscopic techniques: clinical considerations, data analysis, and sample size calculations
Authors: Frank van den Broek, Teaco Kuiper, Evelien Dekker, Aeilko Zwinderman, Paul Fockens, Johannes Reitsma
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Novel imaging techniques need to be evaluated for their ability to improve the detection of polyps. Critical appraisal of reported studies reveals remarkable differences in study designs, despite their similar objectives. The aim of the current study was to compare frequently used study designs for their required sample size to detect relevant differences in polyp detection rates. <b>Patients and methods:</b> Three commonly reported study designs were compared: design 1, the parallel randomized design; design 2, the randomized cross-over design with direct removal of polyps; and design 3, the randomized cross-over design without direct removal of polyps. A total of five different scenarios were analyzed per study design, representing a variety of clinical settings. Each scenario was repeated 1000 times for each study design and the sample size that produced a significant result per study design in each scenario was recorded. <b>Results:</b> In many scenarios, study design 1 required 10 – 15 times more patients to reach the same statistical power of 80 % compared with study design 2. Further reductions in sample size could be achieved when study design 3 was used, although this design is limited by its impracticality. <b>Conclusions:</b> The randomized parallel design requires a larger sample size to achieve equivalent power to the cross-over design. Researchers should carefully consider whether the latter design could be used instead, as it requires a lower number of subjects, although it may be more cumbersome for patients, endoscopists, and researchers.