tbuckley/cabot-search huggingface dataset:
SAT0273 Lower socioeconomic status and smoking are associated with greater radiographic disease severity in axial spondyloarthritis:
Authors: L.S. Gensler, G. Yoon, T.J. Learch, M.M. Ward
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Radiographic severity and progression are important outcome measures in Ankylosing Spondylitis (AS). In the past, the Bath Ankylosing Radiology Index (BASRI) was the primary measure used. More recently, the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) has been studied. However, most recent studies have reported on radiographic disease progression, not severity. Prior studies that have used the BASRI for radiographic severity have looked at patients with long-standing disease. <h3>Objectives</h3> To determine the clinical and demographic characteristics associated with radiographic spinal disease severity, as defined by the mSASSS in a heterogeneous single-center cohort of patients with axial Spondyloarthritis (SpA). <h3>Methods</h3> This is a cross-sectional analysis from the baseline visits for patients consecutively enrolled at one center. Patients were enrolled if they met Assessment of SpondyloArthritis (ASAS) criteria. Radiographs were performed at baseline (including Pelvis and spinal films). Clinical and demographic features were assessed by univariate analysis and then by Multivariate linear regression. <h3>Results</h3> One-hundred-and-seventy patients were enrolled. of which, 73.5% met Modified New York (NY) criteria for AS and 26.5% met ASAS criteria for axial SpA. Of those not meeting modified NY criteria, all but 2 had radiographic sacroilitis. This was an ethnically diverse group, with Caucasian patients accounting for 60% of the cohort. Baseline characteristics are outlined in the table 1. Of 170 patients, 138 had complete data available for analysis. In the multivariate analysis, a higher mSASSS was associated with male gender (coefficient = 5.52, p=0.02, 95% CI 0.81; 10.23), disease duration (coefficient = 0.54, p&lt;0.0001, 95% CI 0.31; 0.77), older age at onset (coefficient = 0.31, p=.02, 95% CI .05; .56) a lower socioeconomic status (SES), as defined by years of education (coefficient = -1.12, p=0.002, 95% CI -1.83; -0.41) and smoking (in pack-years) (coefficient = 0.5, p=0.001, 95% CI 0.21; 0.79). There was a trend to significance with non-Caucasian ethnicity (coefficient = -3.96, p=0.08, 95% CI -8.32; 0.4) and having a first-degree relative with AS (coefficient = 5.12, p=0.08, 95% CI -0.55; 10.78). Table 1. Baseline characteristics and Univariate analysis <h3>Conclusions</h3> Lower SES and smoking are independently associated with greater radiographic disease severity in Axial SpA. Further studies are needed to explore the relationship of how SES relates to radiographic damage and how smoking affects bone health in Axial SpA. <h3>References</h3> Michael M. Ward, Matthew R. Hendrey, James D. Malley et al., Arthritis Care &amp; Research 2009 Vol. 61(7): pp. 859-66 <h3>Disclosure of Interest</h3> None Declared
Correlation between Histopathological Diagnosis and Real-Time Tissue Elastography Scores.
Authors: Y. Nishiyama, U. Sakaguchi, K. Matsushita, A. Kawagoe
Journal: Cancer Research (2009)

Abstract Background“Hardness” is important characteristics of carcinoma. Recent invention of Real-time Tissue Elastography (EG) has made scaling the hardness possible. At 31st SABCS, we reported that B-mode ultrasound(US)+mammography(MMG)+EG demonstrated high sensitivity even for the malignancy of the mass-forming lesions of 1.1 cm or smaller in diameter. This results suggested that possibility of a mass-forming lesion being malignant is ignorable low when it is judged as “not malignant” by this combined method. In this study, we verified correlation between EG score and histopathological diagnosis.Method416 patients with mass-forming and non-mass-forming breast lesions (118 malignant, 298 benign) whose tissues were diagnosed by histopathologically from October 2007 to March 2009 were studied. The hardness was scored on a scale 1 to 5 on Tsukuba elasticity scoring system.ResultsIn mass-forming breast lesions, the mean overall score of malignant diseases was 4.1 (invasive carcinoma 4.3, noninvasive carcinoma 3.5), and the mean overall score of benign diseases was 2.4, and thus scores of malignant diseases were significantly high (&amp;lt; 0.0001). On the other hand, in non-mass-forming breast lesions, the mean overall score of malignant diseases was 2.3 (invasive carcinoma 2.5, noninvasive carcinoma 2.4), and the mean overall score of benign diseases was 2.0, and thus no differences were seen between them. Furthermore, for examination by mass-forming lesions combined with non-mass-forming lesions the mean score of noninvasive carcinomas was 2.5.ConclusionIt was found that in mass-forming lesions, high scores suggest invasive carcinoma and low scores suggest benign diseases. However, as in non-mass-forming lesions, both invasive and noninvasive carcinomas almost show no high EG scores, it appeared necessary to look into invasive examinations such as biopsy for the diagnosis of non-mass-forming lesions. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5026.
Abstract LB-302: Coordinate upregulation of pluripotency factors in a hybrid epithelial/mesenchymal state in anoikis resistant suspended breast epithelial cells
Authors: Anne Grosse-Wilde, Adrian Ozinsky
Journal: Cancer Research (2012)

Abstract Epithelial cells have an absolute requirement for surface adhesion for survival, and loss of adhesion activates apoptosis, a process named anoikis. During metastasis, cancerous epithelial cells are able to survive anoikis after they have spread from the primary site of the tumor. The mechanisms underlying anoikis survival are not well understood, but include cell lineage switching from epithelial to mesenchymal behavior, implying a role for stem cells. Several studies have shown that the mesenchymal population of tumorigenic breast cells contains stem cells, yet it appears that only a small yet unknown subpopulation of the mesenchymal cells is able to survive the strong selection pressure to survive anoikis in suspension and proliferate to form mammospheres. These studies have been complicated by the fact that heterogeneous cell lines consisting of epithelial and mesenchymal cells were analyzed, obscuring the role of small but possibly relevant subpopulations. Here, we were employing both single cell-derived homogeneous mesenchymal cell clones as well as novel microfluidics-based high throughput qRT-PCR analysis to unravel gene expression in epithelial and/or mesenchymal breast cancer cells during survival of anoikis. We show evidence that during culture of transformed mammary epithelial cells (HMLER) in suspension certain subpopulations disappear and then get repopulated by the surviving, proliferating and differentiating subpopulation in suspension. During this period in suspension critical for repopulation we find coordinate expression of both epithelial and mesenchymal markers, rapid upregulation of pluripotency factors (such as OCT4 and Nanog), as well as of several other genes that have previously been described to indicate poor prognosis for breast cancer survival. Those poor prognosis markers we also found elevated in replated and passaged anoikis-resistant HMLER cells as well as in HMLER-derived mesenchymal clones. By contrast expression of pluripotency factors was only restricted to the suspended state. In conclusion, here we show that in suspended breast epithelial cells there exists an epithelial/mesenchymal hybrid state likely to give rise to differentiated progenies, being able to adapt to the diverse challenging environments such as at secondary metastatic sites in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-302. doi:1538-7445.AM2012-LB-302
A8.05 Mirnas expression in systemic lupus erythematosus
Authors: R Shumnalieva, D Kachakova, S Monov, R Kaneva, Zl Kolarov, R Rashkov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by autoantibody production, complement activation and deposition of immune complexes in tissues and organs. Its pathogenesis is still unknown but recent studies reveal the biological and clinical relevance of altered microRNAs (miRNAs) expression in SLE – in serum, peripheral blood (PB) monocytes, T- and B-cells. The aim of our study was to evaluate the diagnostic and prognostic value of PB expression levels of miR-146a and miR-155 in SLE patients. <h3>Materials and methods</h3> 40SLE patients according to the 1981 ACR criteria were included in the study. miR-155 and -146a expression levels in whole PB samples were determined by PCR (SYBR Green technology) and 2<sup>-∆∆Ct </sup>method was used for analysis. 32 healthy donors were usedas controls. SPSS v20 was used for ROC curve and Spearman correlation analysis. <h3>Results</h3> ROC curve analysis showed that the expression levels of miR-146a (AUC-0.711, p = 0.002) in PB better discriminate SLE patients from HCs with 82.5% sensitivity and 56.2 % specificity in comparison to miR-155 (AUC-0.691, p = 0.005, 77.5% sensitivity and 50.0% specificity). Diagnostic accuracy did not improve much when combination of the studied miRNAs was used in multimarker ROC curve analysis (AUC-0.716, p = 0.002, 82.5% sensitivity and 56.2% specificity). miR-146a and miR-155 showed statistically significant correlation with diagnosis (r<sub>s</sub> = 0.363 and 0.330, respectively) and age (r<sub>s</sub> = 0.239 and 0.366, respectively). miR-155 showed also correlation with the presence of secondary Raynaud syndrome with Spearman correlation coefficient 0.250. <h3>Conclusions</h3> Our data showed that the expression levels of miR-146a and miR-155 in PB could be used as diagnostic biomarkers for SLE in Bulgarian patients but larger study is needed to confirm these results. <h3>Acknowledgement</h3> The study was supported by Grant 53/2014 funded by Medical University&nbsp;– Sofia, Bulgaria.
Abstract 4781: XIAP expression is associated with poor prognosis and is a promising therapeutic target for the treatment of papillary thyroid carcinoma
Authors: Azhar R. Hussain, Prashant Bavi, Rong Bu, Maqbool Ahmed, Abdulrehman Al-Nuaim, Mohammed Ahmed, Saif Al-Sobhi, Tarek Amin, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract The inhibitor of apoptosis protein (IAP) family member, X-linked Inhibitor of Apoptosis Protein (XIAP) is essential for cell survival in variety of cancers. However, the role of XIAP overexpression in papillary thyroid carcinoma (PTC) is not fully elucidated. Therefore, we analyzed the expression of XIAP protein and its clinico-pathological correlation in a large cohort of Middle Eastern PTC by immuno-histochemistry in a tissue micro-array format followed by in vitro studies using PTC cell lines. XIAP was found to be over-expressed in 25% of PTC and directly associated with older age (p&amp;lt;0.0001) and presence of extra-thyroidal extension (p&amp;lt;0.0001). Interestingly, XIAP was also found to be significantly associated with tall-cell variant (p=0.0013), larger tumor size (p=0.0002) and advanced stage (III and IV) disease (p&amp;lt; 0.0001). XIAP over-expression was also significantly associated with over-expression of oncogenic c-Met (p=0.0010) and anti-apoptotic Bcl-Xl protein (p&amp;lt;0.0001). Finally, PTC with XIAP over-expression showed a significantly poor disease free survival (p=0.0476) of 63.1 months as compared to the PTC's with low XIAP expression (74.0 months). Our in vitro data showed that embelin, a selective inhibitor of XIAP, caused a dose dependent inhibition of cell proliferation in PTC cell lines. Furthermore, we found that embelin induced a dose dependent apoptosis as detected by cell cycle analysis and annexin V/PI dual staining in PTC cells. On further analysis, our data showed that embelin induced a caspase-dependent apoptosis of PTC cells via activation and cleavage of capsases-9 and -3 and cleavage of PARP. In summary, our clinical data highlights the fact that XIAP over-expression in PTC confer a aggressive phenotype with poor outcome. In vitro studies using XIAP inhibitor suggest that this sub-group of PTC with over-expression of XIAP can be therapeutically targeted to induce efficient apoptosis in these cancers. 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 4781. doi:10.1158/1538-7445.AM2011-4781
Abstract 2795: Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Jason B. Douglas, Debra T. Silverman, Michael N. Pollak, Yuzhen Tao, Amr S. Soliman, Rachael Z. Stolzenberg-Solomon
Journal: Cancer Research (2010)

Abstract Experimental evidence suggests that an overexpression of insulin-like growth factor-I (IGF-I) is implicated in human pancreatic tumors. Moreover, increased IGF-II and decreased insulin-like growth factor binding protein-3 (IGFBP-3) concentrations are found in a number of cancers. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55-74 years of age at baseline, to test whether pre-diagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n=374),who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex and date of blood draw. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for smoking. In the multivariable adjusted model, IGF-I, IGF-II, and IGFBP-3 concentrations were not associated with pancreatic cancer (highest compared with lowest quintile, OR=1.23, 95% CI 0.67-2.25, p-trend=0.12; OR=0.98, 95% CI 0.52-1.85, p-trend=0.52; and OR=1.15, 95% CI 0.62-2.16, p-trend=0.90). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels in the smoking-adjusted model (OR=1.46, 95% CI 0.78-2.74, p-trend=0.04). A higher IGF-I/IGFBP-3 molar ratio may represent increased free IGF-I and be a risk factor for pancreatic cancer. 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 2795.
Claim that primary care provides in excess of 80% NHS activity is wrong
Authors: P. D. Miller
Journal: BMJ (2013)

Lumb states that primary care provides “in excess of 80% NHS activity.”1 Although such comments are often made, even by senior representatives of the Royal College of General Practitioners, it is not true and does not stand up to reason or analysis.

The NHS staff survey September 2012 for England shows 100 899 full time equivalent doctors in …
P1-04-07: Poly (ADP-Ribose) Polymerase-1 (PARP-1) Is Overexpressed in Human Breast Cancer Stem Cells: Results from a Proteomic-Based Approach.
Authors: M Gilabert, C Ginestier, S Audebert, M Pophillat, Y Toiron, D Birnbaum, J-P Borg, E Charafe-Jauffret, A Gonçalves
Journal: Cancer Research (2011)

Abstract Introduction: Cancer stem cells (CSC) have been increasingly recognized as playing a major role in various fields of breast tumor biology including carcinogeneis, metastasis and resistance to cytotoxic drugs and radiotherapy. Identification of protein biomarkers associated with breast CSC may help understanding CSC biology as well as identifying novel diagnostics and specific therapeutic targets. 2-D Fluorescence Difference Gel Electrophoresis (2-D DIGE) is a method that labels protein samples with fluorescent dyes before 2-D electrophoresis, enabling accurate analysis of differences in protein abundance between samples. Methods: Using flow cytometry-based ALDEFLUOR assay (ALD), we isolated CSC-enriched (ALD-positive) and non CSC-enriched (ALD-negative) cell populations of MDA-MB-453, a human breast cancer cell line. Total proteins were extracted from both fractions using urea-based buffer and subjected to 2D-DIGE. Differentially expressed spots were excised, proteins were gel-extracted, digested and identified using MALDI-TOF MS (Ultraflex, Brucker Daltonics, Billerica, USA) Results: 2D-DIGE revealed differential expression of various protein spots between ALD-positive and ALD-negative MDA-MB-453 cells. MALDI-TOF MS analysis allowed identification of 11 differentially expressed proteins, among which 7 were down-regulated and 4 were up-regulated in ALD-positive MDA-MB-453 cells, including Poly (ADP-ribose) polymerase-1 (PARP-1). Overexpression of PARP-1 in MDA-MB-453 cells was further confirmed by western blot using specific monoclonal antibody and such an observation was extended to 4 additional human breast cancer cell lines including HCC1937, MDA-MB-436, SUM149 and SUM159. These 5 human breast cancer cells were found to display a limited short-term sensitivity (within the micromolar range) to olaparib, a specific PARP-1 inhibitor. However, a negative correlation was found between the level of overexpression and the ability of olaparib to inhibit the growth of ALD-positive cells. Conclusion: A proteomic-based approach revealed that PARP-1 was up-regulated in ALD-positive, CSC-enriched from various human breast cancer cell lines. Such an overexpression may contribute to clinical resistance to PARP-inhibitors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-07.
Comparison of MRI tumor volumetric and diameter measurements for predicting recurrence free survival in breast cancer patients undergoing preoperative chemotherapy.
Authors: DC Newitt, J Gibbs, SC Partridge, KL Li, EC Lobo, L Esserman, NM Hylton
Journal: Cancer Research (2009)

Abstract Abstract #6053 Background: Assessment of tumor response to chemotherapy has traditionally relied on the bidimensional tumor measurement guidelines proposed by the World Health Organization (WHO, 1979) and more recently on the unidimensional Response Evaluation Criteria in Solid Tumors (RECIST, Therasse et al., 2000). MRI is being used increasingly to monitor breast cancer response to preoperative chemotherapy and allows both linear and volumetric assessment of tumor size. The purpose of this study was to compare pre- and post-treatment RECIST, WHO, and volumetric measures of tumor size on MRI for predicting recurrence free survival (RFS) in patients undergoing preoperative chemotherapy.&amp;#x2028; Materials &amp; Methods: 56 patients with locally advanced breast cancer were imaged with MRI (1.5T GE scanner) before and after 4 cycles of preoperative chemotherapy. Tumor longest diameter (LD) at physical exam (ClinLD) was recorded before (N=56) and after (N=48) treatment. Fat suppressed, contrast enhanced, T1-weighted sagittal 3DFGRE images (TE/TR=8/4.2ms, flip=20°, 2mm thick, 18-20cm FOV, 256x192 matrix) were acquired for tumor size measurements.&amp;#x2028; All MRI LD measurements were made manually following RECIST and WHO guidelines. Tumor volume was measured with a semi-automated tumor segmentation algorithm based on a specific enhancement ratio calculation. Univariate Cox proportional hazards analysis was used to assess the value of clinical, pathology, RECIST, WHO, and volume measurements for predicting RFS. Variables with p&amp;lt;0.15 were combined in a stepwise multivariate model to determine the greatest predictive value.&amp;#x2028; Results: 23 patients have recurred since surgery (mean time 132 weeks). The mean RFS in the non-recurrent group is 330 weeks. Results for univariate and multivariate analysis are show in the Table. Final tumor volume was most predictive of recurrence free survival, and was the only variable found to be an independent significant predictor in the multivariate analysis. Age, tumor grade, and positive lymph node status were not significant predictors.&amp;#x2028; Discussion: Post-chemotherapy tumor volume calculated via a semi-automatic algorithm was found to be a significant predictor of RFS for patients undergoing preoperative chemotherapy, out-performing manual 1D RECIST, 2D WHO, and clinical measurements. The results support previous work demonstrating the value of MRI tumor volume for predicting patient outcome.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6053.
Abstract 169: The origin of colorectal cancer with CpG island methylator phenotype
Authors: Minoru Toyota, Eiichiro Yamamoto, Hiromu Suzuki, Seiko Kamimae, Hiro-o Yamano, Yasuhisa Shinomura, Kohzoh Imai
Journal: Cancer Research (2010)

Abstract Colorectal cancers (CRCs) are divided into three different subclasses based on the genetic and epigenetic profiles: CpG island methylator phenotype (CIMP) 1, CIMP2 and CIMP-negative. CIMP1 has been shown to be associated with BRAF mutations and sessile serrated adenoma. CIMP2 has been shown to be associated with KRAS mutation, but precursor lesions of CIMP2 remain to be determined. Our aim of this study is to identify the origin of CRCs with CIMP by examining the promoter methylation of tumor-related genes and genome-wide methylation profiles in precursor lesions. Based on histological examination after endoscopic mucosal resection or operation, the specimens were divided into two groups: 65 serrated polyps (SPs), 109 colon adenomas (ADs) with or without high grade dysplasia. Endoscopically, subsets of SPs were composed of flat and protruded lesions, and biopsy samples were obtained from both lesions, and were divided into three groups: flat lesions only (SP1, 19 cases), flat lesions adjacent to protruded lesions (SP2, 21 cases), or protruded lesions adjacent to flat lesions (SP3, 25 cases). Mutations of BRAF were observed frequently in SPs but not in ADs (26% vs 2%), indicating that the SPs are the origin of CIMP1 characterized by BRAF mutations and microsatellite instability as suggested previously. Frequencies of KRAS mutations were highest in tubulovillous adenomas (TVs) followed by SPs, and tubular adenomas (TAs) (57% vs 43% vs 20%). High frequency of KRAS mutations in SPs and TVs prompt us to examine genome-wide methylation profiles in these tumors. By hierarchical clustering analysis of the MCAM results, SP3, SP1/SP2, and normal colon were grouped into three distinct clusters, and it is suggested that genome-wide methylation occurs during the course of progression from SP2 to SP3, and was associated with acquirement of CIMP. We further examined methylation profiles of additional SPs, ADs (TVs and TAs) with KRAS mutations. Cluster analysis of KRAS mutant SPs and ADs grouped tumors into three clusters; cluster-1 with genome-wide aberrant methylation, cluster-2 with moderate methylation, and cluster-3 with little methylation. Cluster-1 contained SP3 and majority of TVs, cluster-2 contained SP1, SP2, and TAs, and cluster-3 contained normal colon. The present study suggested that CRCs with CIMP2 are originated from two distinct subgroups; CIMP2-protruded (CIMP2-P) originated from serrated-villous protruded tumors, and CIMP2-depressed (CIMP2-D) originated from tubular-depressed pathway. 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 169.