tbuckley/cabot-search huggingface dataset:
A1.2 High Throughput analysis of IGG fab glycosylation reveals differences between RA-patients and healthy controls during pregnancy and after delivery
Authors: Albert Bondt, Yoann Rombouts, Johanna M W Hazes, Manfred Wuhrer, Radboud J E M Dolhain
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is known to improve during pregnancy, and flare after delivery [1].1] This correlates with changes of the N-glycosylation pattern in the constant region (Fc) of immunoglobulin (Ig) G [2, 3].2, 3] In addition to Fc-glycosylation, 15-25% of IgG antigen binding fragments (Fab) carry N-glycans [4].4] These Fab-linked N-glycans have been suggested to influence affinity to antigen and antibody half-life whereas their role in pregnancy and RA remains unclear [4, 5].4, 5] Our objective was to explore IgG Fab glycosylation of RA patients compared to healthy controls during pregnancy and after delivery, and compare it to Fc glycosylation. <h3>Materials and Methods</h3> Sera were collected preferably before conception (T1, only RA-patients), at three times during pregnancy (T2-4) and three times after delivery (T5-7) from RA-patients (n = 28) and healthy controls (n = 29) participating in the PARA-study, a prospective cohort study on the effect of pregnancy on RA. IgG was affinity purified from 5 µL serum. Using IdeS enzyme IgG was cleaved in two ½ Fc portions and a F(ab')<sub>2</sub> portion. Fc and F(ab')<sub>2</sub> were separated, and glycans were released, followed by automated MALDI-TOF measurement to establish the levels as well as patterns of glycosylation. <h3>Results</h3> At all six time points during pregnancy and after delivery, Fab portions of RA-patients show a significant higher level of neutral glycans compared to healthy controls (T2-T5 p&lt;0.0001; T6 p&lt;0.05), which occurs at the expense of galactosylated and sialylated species. Consequently, lower levels of disialylated glycans are observed in RA-patients compared to controls (p&lt;0.001; except for T7: p = 0.28). Relative to Fc-glycans, Fab-linked N-glycans of RA-patients exhibit higher levels of galactosylation (Fab: 86% (SD 9%); Fc: 54% (9%)), sialylation (Fab: 50% (4%); Fc: 16% (4%)) and bisection (Fab: 48% (7%); Fc: 14% (3%)). Similar results were obtained for controls. In addition, comparison of the 3<sup>rd</sup> trimester and pre-conception state showed changes for bisection (48 to 40%; p&lt;0.005) and fucosylation (63 to 57%; p&lt;0.05). After delivery bisection was found to change significantly in patients (42 to 47%; p&lt;0.005). No other pregnancy related changes in glycosylation were observed for Fab-linked N-glycans. <h3>Conclusions</h3> IgG Fab glycosylation is different for RA patients compared to healthy controls. As for Fc glycosylation, lower levels of galactosylation and sialylation can be observed on the Fab of RA patients. Furthermore, glycosylation of the Fab portion differs from Fc glycosylation. In contrast to glycosylation of the Fc, Fab glycosylation shows less pregnancy-associated changes over time.
AB0188 The serum levels of adipocytokines (leptin, adiponectin and resistin) in ankylosing spondylitis patients
Authors: C.T. Chou, W.S. Chen, Y.S. Chang, C.C. Lai, S.H. Wang, M.H. Chen, C.Y. Tsai, K.H. Hsiao, H.T. Lee
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is evidence that adipocytokines play an important role in metabolism and in inflammation. Adipocytokines are involved in numerous rheumatic diseases, such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus. They exert potent modulatory actions on target tissues and cells in rheumatic diseases, including cartilage, synovium and immune cells. <h3>Objectives</h3> The aim of our study is to determine the serum leptin, adiponectin and resistin levels in patients with ankylosing spondylitis (AS) and to investigate the relationship with disease activity markers. <h3>Methods</h3> Leptin, adiponectin and resistin serum levels were measured in 50 AS patients and in 20 matched healthy control using commercially available enzyme-linked immunosorbent assays. Leptin, adiponectin, and resistin levels were correlated with clinical parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Disease Functional Index (BASFI), and Bath AS global score (BASG). <h3>Results</h3> AS patients exhibited significantly higher resistin [Mediun (interquartile range) 3.6 (2.3∼5.1) vs. 2.7 (1.9∼3.4) μg/ml, p=0.03], but no difference in leptin and adiponectin levels [31.9 (18.9-58.9) vs. 30.3 (11.9∼83.9) ng/ml; [28.5 (14.6∼51.4) vs. 24.5 (13.6∼48.5), respectively p=NS)]. No correlation was found between leptin, adiponectin, and erythrocyte sedimentation rate, c-reactive protein levels, or BASDAI, BASFI and BASG. The resistin level was correlated with BASDAI (r: 0.364; p=0.013). There are no changes in serum adipokine concentrations after 3 months TNF blocker treatment. <h3>Conclusions</h3> Serum level of resistin are increased in patients with AS and correlated with BASDAI. Further studies are needed to elucidate the role of adipocytokines in AS. <h3>Disclosure of Interest</h3> None Declared
Follow-Up of Sweat Gland Carcinoma by FDG-PET Imaging
Authors: HALUK ALBAZOGLU, DAVID MEGREMIS, AMJAD ALI, GREGORY LAMONICA
Journal: Clinical Nuclear Medicine (1998)

Sweat gland carcinoma is a rare malignancy of the skin with a poor prognosis. The principal mode of therapy has been local surgical excision, which may be supplemented by adjuvant chemotherapy and radiotherapy. More than 50% of patients develop either local tumor recurrence or regional lymph node metastases after surgery. The authors report a case of sweat gland carcinoma in which recurrence was detected by F-18 FDG PET imaging. FDG PET imaging can be helpful in early detection of local recurrence.
Letter to the editor: Preventing nosocomial MRSA infections by screening
Authors: H A Verbrugh
Journal: Eurosurveillance (2014)

Preview this article: Letter to the editor: Preventing nosocomial MRSA infections by screening, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/37/art20901-en-1.gif
Abstract 5616: Assessment of differential DNA methylation by genotype in ovarian cancer cases and controls
Authors: Mine S. Cicek, Sebastian M. Armasu, Kimberly R. Kalli, Brooke L. Fridley, Thomas A. Sellers, Ya-Yu Tsai, Julie M. Cunningham, Ellen L. Goode
Journal: Cancer Research (2011)

Abstract Ovarian carcinoma is a significant cause of cancer mortality in women in the United States. Increasing evidence has demonstrated that differential methylation status in lymphocyte DNA may be linked to risk of carcinogenesis. We are investigating the differential DNA methylation in germline DNA obtained from pre-treatment ovarian cancer cases (n=256) and individually-age matched controls (n=274) using the Illumina Infinium Human Methylation 27K BeadChip. We are first studying methylation and the common moderate-risk alleles for ovarian cancer on chromosomes 2q31, 3q25, 8q24, 9p22, 17q21, and 19p13. Within each locus, we correlated single nucleotide polymorphism (SNP) genotypes with methylation values at relevant nearby CpG sites. Preliminary results are available on the first set of 84 cases and 90 controls. At 2q31, cases with TG or TT genotype at rs2072590 were hypomethylated at HOXD1 (a homeobox transcription factor) compared to cases with GG genotype (mean beta TG/TT=0.08, GG=0.09, p=0.034); and at 17q21, cases with AG or GG genotype at rs9303542 were hypomethylated at SKAP1 (a T-cell adaptor protein) compared to cases with AA genotype (mean beta AG/GG=0.14, AA=0.16, p=0.045). At these two loci, similar trends were seen among controls. Logistic regression adjusted for age and methylation chip was then used to assess the association between SNP genotype and ovarian cancer risk, with and without inclusion of the relevant methylation value. At HOXD1 rs2072590, the per-allele ovarian cancer risk of 1.34 attenuated to 1.25 with inclusion of the HOXD1 methylation value as a covariate, suggesting that the disease association may be mediated in part through methylation. Though based on preliminary data, results are consistent with a role for inherited variation on germline methylation at HOXD1 and SKAP1. Analysis of methylation on additional genotyped cases and controls is underway. Finally, because, trans effects may also exist, we are assessing relationships between genotype and methylation at other loci throughout the genome. Such correlative molecular studies have the potential to help elucidate mechanisms underlying associations from genome-wide association studies. 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 5616. doi:10.1158/1538-7445.AM2011-5616
Abstract 4540: Pyruvate kinase M2 (PKM2) associated with poor prognosis in gastric signet ring cell carcinoma
Authors: Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Journal: Cancer Research (2012)

Abstract Background: PKM2 (M2 isoform of pyruvate kinase) was identified as a driver of aerobic glycolysis, leading to cell growth and tumor development. PKM2 is usually known to overexpress in cancer, however, there are still remaining questions about the function and the potential as anti-cancer treatment target. We investigated the expression status of PKM2 in gastric cancer tissues and evaluated the possibility of biomarker and anticancer target. Methods: Paraffin-embedded tissue microarray blocks of gastric adenocarcinoma tissue specimens were obtained from 363 gastric cancer patients. All patients underwent curative gastric resection from 1999 to 2007 and distributed from stage I to IV and their clinical characteristics were collected. IHC (Immunohistochemical) assay was performed to evaluate PKM2 expression levels. The correlation of PKM2 expression level with gastric cancer prognosis / stage / histology was evaluated. Results: In our previous microarray study using 60 gastric cancer tissues, we identified PKM2 mRNA overexpressed in cancer tissue than non-cancer tissue (P&amp;lt;0.01). In IHC assays, PKM2 expression level was classified to score 0 (negative, n=185), 1 (weak positive, n=136), and 2 (strong positive, n=42). 49% of gastric cancer tissues presented PKM2 expression (weak or strong positive). PKM2 expression had no relation with prognosis (p=0.913, recurrence free survival) and TNM stage (p=0.825). Intestinal and diffuse type cancer manifested different PKM2 expression pattern and signet ring cell carcinoma manifested 26.6% PKM2 expression. Within same Lauren classification, there was no significant difference of prognosis according to PKM2 expression except signet ring cell carcinoma. In signet ring cell cancer (n=78), PKM2 expression was related to poor overall survival (p=0.029) Conclusion: PKM2 protein expression was not correlated with gastric cancer prognosis. Only in signet ring cell gastric cancer, overexpressed PKM2 was associated with poor overall survival. The role of PKM2 should be further verified in signet ring cell gastric cancer model to find clinical significance in this subtype of gastric cancer. 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 4540. doi:1538-7445.AM2012-4540
729 VARIABLES RELATED TO INADEQUATE LIVER STIFFNESS MEASUREMENTS USING TRANSIENT ELASTOGRAPHY. ANALYSIS OF 895 EXAMINATIONS
Authors: M. Puigvehí, J.A. Carrión, S. Coll, M. García-Retortillo, N. Cañete, I. Cirera, M.D. Gimenez, C. Márquez, F. Bory, R. Solà
Journal: Journal of Hepatology (2013)
PTH-055 To Evaluate the Frequency and Risk Factors in the Post Ercp Pancreatitis where Ercp Accessories are Reused
Authors: S Ghazanfar, S Qureshi
Journal: Gut (2013)

<h3>Introduction</h3> Despite all the advances and improvement in ERCP techniques, post ERCP acute pancreatitis remains the most feared and common complication, being associated with high morbidity and mortality. The figures cited in literature vary from 1–7% to 12–31%. The pathogenesis of this condition is multifactorial and the severity of the condition may range from mild to severe pancreatitis. Most of the cases are of mild pancreatitis which usually resolves spontaneously without serious sequelae. The incidence of severe pancreatitis ranges from 0.3% to 0.6%. The objective of our study was to look at the frequency of post ERCP pancreatitis in a setup, where ERCP accessories are reused because majority of the patients cannot afford the cost of new accessories for the procedure. Another objective was to look at the factors responsible for acute pancreatitis. <h3>Methods</h3> This study was conducted at the endoscopy suite of surgical unit IV, Civil Hospital Karachi over a period of one year from 1st December 2010 to 30th November, 2011. A total of 500 patients were included in the study. Patients who presented with pancreatitis or raised amylase levels pre procedure or patients who had previous history of surgery on the biliary or pancreatic systems were excluded from the study. Pearson Chi square and Fisher’s exact test were used for qualitative data and t-test for quantitative data. Significance was taken as p≤ 0.05. Odds ratio was calculated for the qualitative data using 95% confidence interval. <h3>Results</h3> Age of the study population ranged from 9 to 90 years (mean age 46.5 years ±14.94, median 45 years). Male to female ratio was 1:1.87. Pancreatitis was seen in 18 patients (3.6%). Mild in 15(3%), moderate in 1(0.2%) and severe in 2(0.4%). Mean amylase level at 4 hours and 24 hours was 280.93±539.13 and 168.83 ± 338.34 respectively. Pancreatitis was seen in 15/326 (4.6%) female and 3/174 (1.72%) males. Statistically significant increased risk for pancreatitis was seen in difficult cannulation (9.8%, p = 0.006), prolonged cannulation time (7.6min, p = 0.002), pancreatic duct cannulation (13.7%, p = 0.001) and pancreatic duct contrast injection (13.4%, p &lt; 0.001). <h3>Conclusion</h3> The frequency of pancreatitis was comparable to that of international literature. Difficult cannulation, pancreatic duct cannulation, pancreatic duct contrast injection and balloon sphincteroplasty increases the incidence of post ERCP pancreatitis. Reuse of ERCP accessories poses no additional risk to the frequency of pancreatitis. <h3>Disclosure of Interest</h3> None Declared.
SAT0564 The Prevalence of Moderate to Severe Radiographically Verified Sacroiliitis and the Correlation with Health Status in Elderly Swedish Men - The Mros Study
Authors: S. Exarchou, I. Johnel-Redlund, M. Karlsson, D. Mellström, C. Ohlsson, C. Turesson, L. E. Kristensen, L. T. Jacobsson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing Spondylitis (AS) is a chronic inflammatory disorder primarily involving the axial skeleton. It starts predominantly before the age of 30 and the hallmark for the diagnosis is the detection of sacroiliitis on x-rays. Estimates of the prevalence of AS ranges from 0.03% and 1.8% in Europe<sup>1</sup>. However, there is limited data on the prevalence of radiographically verified sacroiliitis. <h3>Objectives</h3> To estimate the prevalence of moderate to severe radiographically verified sacroiliitis (grade 3-4) in a population based study of elderly men and compare the health status in those with and without sacroiliitis. <h3>Methods</h3> A population survey for the study of risk factors for osteoporosis (MrOS)<b><sup>2</sup></b> including 1005 men 69-81 years old, randomly identified from the regional population registry was used. X-rays of the pelvis and spine were examined by two readers and the prevalence of grade 3-4 sacroiliitis, syndesmophytes and spondylophytes were ascertained. Self-administered questionnaire registered data on demographics, anthropometrics, lifestyle, physical activity (PASE), functional status (IADL items), quality of life (SF-12) and back health (pain, Quebec Pain Disability Scale items). <h3>Results</h3> Fourteen cases with grade 3-4 sacroiliitis were identified corresponding to a prevalence of 1.4% (95%CI: 0.7-2.4). There were 7 with sacroiliitis grade 3 bilaterally, 4 with grade 4 bilaterally, 1 with grade 3 involvement at one SI-joint and grade 4 at the other and only 1 with unilateral grade 3 involvement. All patients with sacroiliitis had either syndesmophytes and/or bridges or degenerative changes in the spine. The majority (8/14) had both types of changes, 4 had no syndesmophytes and 2 no spondylophytes. There were no major differences between the two groups regarding demographics, anthropometric measures and smoking status. Furthermore, there were no significant differences with regard to health status, physical activity or quality of life, although a tendency towards impaired functional status was observed among those with sacroiliitis. The majority of individuals with sacroiliitis did not report major difficulties related to back problems. <h3>Conclusions</h3> The prevalence of moderate to severe (grade 3-4) radiographically verified sacroiliitis was 1.4% in a population of elderly men in Sweden. Self-reported health was only slightly different in those with sacroiliitis, suggesting that the relative impact of AS is modest at this age group. <h3>References</h3> Sieper J, et al. Best Pract Res Clin Rheumatol. 2006 Jun; 20(3): 401-17. Ohlsson C, et al. J Am Coll Cardiol. 2011 Oct 11; 58(16):1674-81. <h3>Disclosure of Interest</h3> None Declared
P3-05-04: Changes in Recurrence Risk of Breast Cancer Intrisic Subtypes over Time.
Authors: N Ribelles, L Perez-Villa, B Pajares, JM Jerez, L Vicioso, B Jimenez, Luque V de, L Franco, M Alvarez, LG Perez-Rivas, A Sanchez-Muñoz, E Gallego, A Marquez, I Hierro, E Alba
Journal: Cancer Research (2011)

Abstract Background: Gene expression profiling and their immunohistochemistry-based surrogates have consistently revealed prognostically significant breast cancer (BC) subtypes: Luminal A (Lum A), Luminal B (Lum B), HER2, Basal-like (BL) and Triple negative phenotype-nonbasal (TNP-nb). In addition, there are clinical evidence that hazard of BC recurrence varies over time with two peaks of high risk at 18–24 and 60 months. This study compares the time-related patterns of recurrence within BC subtypes. Methods: Tissue microarrays were constructed from 937 early BC patients diagnosed and treated at our Hospital from 1982 to 2005 with available archival paraffin tissue blocks. BC subtypes were defined using an immunopanel of estrogen receptor, progesterone receptor, HER2, epidermal growth factor receptor, cytokeratin 5/6 and Ki67 by prespecified published methods. Univariate and multivariate analysis (Cox regression) were performed on progression-free survival. Smoothed curves for hazard rates (HR) were estimated by a Kernel-like smoothing procedure. The statistical analysis was done by using the R software environment. Results: Cases were classified as follows: Lum A 46.8%, Lum B 25.2%, HER2 11.3%, BL 11.3%, TNP-nb 5.4%. None of the patients were treated with adjuvant trastuzumab. With a median follow up of 80 months age, tumor size, nodal status and intrinsic subtypes were independent prognostic factors. HER2 and BL show high and early peak in HR curves and decreasing sharply to 36 and 48 months respectively. HR in Lum A, Lum B and TNP-nb exhibit a smoother and nearly steady curve. Conclusions: BC subtypes have distinct outcome but also displays different pattern of recurrence over time. These data might imply that pathways underlying early and late recurrences could be different. This additional information would suggest the convenience of considering different timings and duration of adjuvant treatments depending of BC subtypes, and also in the design of surveillance recommendations. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-04.
Abstract 653: Combination of TORC1/2 and MEK kinase inhibitors in colorectal cancer models
Authors: Celina Garcia-Garcia, Violeta Serra, Maurizio Scaltriti, Yasir Ibrahim, Marta Guzman, Katti Jessen, Yi Liu, Christian Rommel, Josep Tabernero, Jose Baselga
Journal: Cancer Research (2011)

Abstract MAPK pathway mutations are frequent in colorectal cancer (CRC) and associated with resistance to standard therapies. This provides a rationale for the use of targeted therapies against the MAPK pathway. However, the response of CRC cells to MEK inhibitors varies depending on coexisting mutations in both MAPK and PI3K pathways. As a matter of fact, dual inhibition of MEK and PI3K or AKT in mouse models of CRC has proven effective due to aberrations in both pathways. Inhibition of TORC1, a shared downstream effector of the MAPK and PI3K pathways, was described to be partly responsible for the efficacy of the dual blockade. In order to explore additional mechanisms involved in the superior antitumor activity of combined MAPK and PI3K pathway suppression we directly targeted TORC1/2 by active-site kinase inhibitor of mTOR, in addition to MEK, in our cell models. We tested the antiproliferative activity of INK128, a selective and potent TORC1/2 inhibitor, in combination with a MEK inhibitor, PD-0325901, in a panel of colon cancer cell lines with diverse alterations of the MAPK and PI3K pathways. PD-0325901 treatment effectively inhibited ERK phosphorylation, which resulted in decreased phosphorylation of Rb and reduced expression of E2F in all the cell lines tested. In CRC cell lines harboring sole mutations in the MAPK pathway, we observed sensitivity to PD-0325901 that was not further enhanced when combining with INK-128. In contrast, CRC cell lines harboring concurrent mutations of both pathways exhibited a striking sensitivity to dual ERK and TORC1/2 blockade associated with an enhanced arrest in cell cycle and, above all, a concomitant increase in apoptosis. Inhibition of TORC1 and TORC2 by INK128 could not be further enhanced by MEK inhibition in any of the cell lines tested. These data suggest that, besides complete suppression of both pathways, additional mechanisms must be at work to explain the observed enhanced cell death following dual suppression of PI3K and MEK. Interestingly, we observed differential regulation of key components of the cell cycle in response to dual blockade. We are currently investigating whether this specific biochemical behaviour plays a causative role in the observed phenotype. In summary, dual inhibition of TORC1/2 and MEK has potential for effective antitumor activity in CRCs with dysregulation of both signaling cascades. A better understanding of the molecular mechanisms responsible for the enhanced efficacy of this therapeutic combination will help defining the best biomarkers that need to be assessed in phase I combination trials. 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 653. doi:10.1158/1538-7445.AM2011-653