tbuckley/cabot-search huggingface dataset:
Abstract 3977: Meta-analysis of posttranslational modifications in cancer
Authors: Peter V. Hornbeck
Journal: Cancer Research (2012)

Abstract PhosphoSitePlus (http://www.phosposite.org) is a comprehensive and easy-to-use resource that includes aggregated information about experimentally observed post-translational modifications (PTMs) observed in over thirty distinct types of cancer. Most of the cancer data is derived from over 900 mass spectrometric datasets of human disease tissues or cell lines, either reported in the literature or from studies performed at Cell Signaling Technology. The four most highly represented diseases are non-small cell lung carcinoma (269 datasets and over 5500 unique sites), breast cancers (99 datasets with over 2630 sites), acute myelogenous leukemia (70 datasets with over 1860 sites), and chronic myelogenous leukemia (115 datasets with over 1700 sites). Users can extract datasets associated with specific diseases, and analyze the data a number of newly-developed analytical tools. These include motif-analysis, permitting users to determine if specific kinases appear to be active in different diseases, and pathway analysis using novel Cytoscape plugins. Datasets and Cytoscape pathways corresponding to specific diseases and other data subsets can be downloaded from the site, enabling users to apply their own bioinformatics analyses to the information available at PhosphoSitePlus. 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 3977. doi:1538-7445.AM2012-3977
Abstract 4679: A multi-stage genome-wide association study on response to chemotherapy in ovarian cancer
Authors: Stuart MacGregor, Yi Lu, Sharon Johnatty, Jonathan Beesley, Xiao Qing Chen, Brooke Fridley, Penny Webb, Howard Gurney, Paul Harnett, Michelle Haber, Ellen Goode, Anna De Fazio, Georgia Chenevix-Trench
Journal: Cancer Research (2011)

Abstract We performed a multi-stage genome-wide association study (GWAS) for drug response in ovarian cancer. We selected 313 chemotherapy treated patients from the Australian Ovarian Cancer Study (AOCS). Patients were treated with paclitaxel/carboplatin and the trait of interest was Progression Free Survival (PFS). We maximized power for a fixed genotyping budget by genotyping individuals from the tails of the distribution: 94 with good survival and 94 with poor survival, taking into account extent of residual disease following surgery. Patients were genotyped on Illumina HumanOmni1-Quad arrays (1140419 loci).Two further cohorts with measures of PFS and whole genome data available; 134 ovarian patients from the Mayo clinic (genotyped on Illumina HumanHap 610 arrays, 620901 loci) and 68 patients from The Cancer Genome Atlas ovarian cancer set (genotyped on Illumina Human1M arrays, 1199187 loci) were meta-analyzed with the AOCS set (stage 1). We have imputed all the stage 1 samples with reference of the 1000 Genome data to allow more direct comparison of SNPs not common to all of the arrays used (up to 6 million SNPs with good imputation quality). Based on the chemotherapy treatment received by each patient, we assigned the patients into primary and secondary analysis, with primary analysis using a more strictly defined treatment subgroup. We followed up the stage 1 findings by genotyping 26 SNPs in more than 3,000 samples collected from 8 study sites of Ovarian Cancer Association Consortium (OCAC). These 26 SNPs were mainly genotyped SNPs, chosen from 23 distinct regions showing the strongest association with chemotherapy response from either primary or secondary analysis. 2 SNPs showed nominal significance in the replication sample (chr 12: rs1861932, chr 22: rs708444). We are currently genotyping more regions to seek replication of the initial findings. In summary, we sought to identify genes that underlie individual differences in chemoresistance. In the future, typing variations in these genes will be important for personalizing drug regimes for patients. 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 4679. doi:10.1158/1538-7445.AM2011-4679
AB0030 Autoantibody Producing CD27-Cd38int Pre-Naive B Cells Have Deficient Capacity to Support CD4+ T Cell Activation in Healthy Individuals, but Exhibit Defective Functions in Systemic Lupus Erythematosus Patients
Authors: J. Lee, J.-H. Sim, H.-R. Kim, I.-J. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Pre-naive B cells are a unique developmental intermediate in human B cell development at developmental stage between transitional and naive B cells. Although immature, pre-naïve B cells were shown to have functions of mature B cells, but their role in immune response is unknown. <h3>Objectives</h3> The aim of our study was to determine the functional role of pre-naive B cells in immune responses. <h3>Methods</h3> Peripheral blood CD27<sup>–</sup>CD38<sup>Int</sup> pre-naïve B cells, CD27<sup>–</sup>CD38<sup>lo</sup> naïve B cells, and CD27<sup>+</sup> memory B cells from healthy individuals and systemic lupus erythematosus (SLE) patients were sorted and stimulated with CD154-L cells. Activated B cells were analyzed for IL-10 and accessory molecule expression, and after co-cultured with sorted CD4<sup>+</sup>CD25<sup>–</sup> T cells, T cell proliferation and cytokine production was measured. After inducing B cells to differentiate into plasma cells, culture supernatant was tested for reactivity of IgM antibodies to ssDNA, dsDNA and histone. Transitional, pre-naïve and naïve B cell were analyzed for IgH CDR3 length and positive charged amino acids. <h3>Results</h3> CD40-stimulated pre-naïve B cells produce high amounts of IL-10. CD40 activated pre-naïve B cells did not suppress CD4<sup>+</sup> T cell cytokine production, but demonstrated IL-10 mediated ineffective stimulation of CD4<sup>+</sup> T cell proliferation. Pre-naive B cells also showed impaired expression of co-stimulatory molecules after CD40 engagement. However, IL-10 is not involved in the differentiation of pre-naive B cells into plasma cells, and IgM antibodies produced by pre-naïve B cells were reactive to ssDNA. SLE pre-naïve B cells were defective in producing IL-10 upon receiving CD40 signal, and costimulatory molecule expression after CD40 engagement was not impaired. <h3>Conclusions</h3> Our data suggest that there is an inherent and IL-10 mediated mechanism that limits the capacity of activated pre-naïve B cells from participating in cellular immune response, but these cells can participate in humoral immune response by production of auto-Abs. Defects in pre-naïve B cell function may result in break in self-tolerance, and could enhance the development of autoimmunity. <h3>Acknowledgements</h3> This work was supported by Basic Science Research Program through the National Research Foundation (NRF) funded by the ministry of Education and Technology (2010-0010589). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4020
SAT0569 Galectin 3 Exerts A Protective Role in A Murine Model of Osteoarthritis
Authors: N. Hafsia, F. Poirier, D. Delacour, P. Reboul, D. Côme, P. Van Lent, M. Cohen-Solal, F. Lioté, H.K. Ea
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) is the most common adult joint disease characterized by cartilage destruction, subchondral bone remodelling and mild synovial inflammation. Pathogenesis of OA involves overload, ageing, genetic factors and chondrocyte dysregulation. Galectin 3 (Gal3) expression is increased in OA cartilage and synovial fluid. Gal3 is involved in multiple cellular functions including proliferation, differentiation and cell death. During embryogenesis, the growth plate of Gal3 mutant mice has a reduction of hypertrophic zone and many lacunae due to a loss of chondrocytes. These results suggest a role of Gal3 in chondrocyte dedifferentiation. <h3>Objectives</h3> To determine the role of Gal3 in osteoarthritis and to assess its functions in chondrocyte biology. <h3>Methods</h3> <i>In vivo</i>, murine OA was induced in Wild type (WT) 129 and Gal3 mutant mice by partial medial meniscectomy (MNX) of the right knee. A sham operation was performed on the left knee. Animals were sacrificed 4 weeks after surgery. Cartilages lesions were assessed according to OARSI recommendations. Chondrocyte apoptosis was assessed by TUNEL labelling and chondrocyte catabolism by immunostaining for aggrecanases and metalloproteases. Subchondral bone modifications were evaluated by microCT. <i>In vitro</i>, primary murine chondrocytes, isolated from new born WT and Gal3 mutant mice, were cultured and stimulated by inflammatory cytokines (IL-1β and TNF-α). Anabolism, catabolic and differentiation responses were assessed by RT-qPCR <h3>Results</h3> <i>In vivo</i>, MNX induced in Gal3 mutant mice more severe OA cartilage lesions compared to WT as assessed by OARSI scoring (4.4±1.0 vs 1.3±0.8, p&lt;0.05). Expression of Gal3 decreased in WT cartilages after MNX compared to sham operated cartilage (34.5% ±4.9 vs 53.0% ±2.8; p&lt;0.01). Cartilages lesions were associated with higher ratio of chondrocyte positive-TUNEL staining in Gal3 mutant cartilages compared to WT (17.7% ±6.2 vs 10.6% ±3.3 p&lt;0.02). Similarly, immunostaining for ADAMTS-5 (26.7% ±0.5 vs 16.0% ±1.4, p&lt;0.02) and VDIPEN (52.0% ±4.0 vs 30.0% ±2.0, p&lt;0.05) was increased in Gal3 mutant cartilages. Moreover, collagen type X expression was increased in Gal3 mutant cartilage. No difference was observed in subchondral bone modifications. In vitro, IL-1β stimulation increased ADAMTS-4 (4.6±2.0 vs; 1.6±0.3, p&lt;0.05) and ADAMTS-5 (4.5±2.2 vs 1.8±1.0, p&lt;0.05) mRNA expressions in Gal3 mutant chondrocytes compared to WT chondrocytes. <h3>Conclusions</h3> Gal3 deletion exacerbated murine OA lesions induced by mechanical stress. OA lesions were associated with increased chondrocyte catabolism, differentiation and death. These results suggested Gal3 had a protective role in OA and chondrocyte homeostasis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4750
Facial Prosthetics Ease Cancer Patient Rehabilitation
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Facial Prosthetics Ease Cancer Patient Rehabilitation Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Pages 998–999, https://doi.org/10.1093/jnci/84.13.998 Published: 01 July 1992
Open-Angle Glaucoma
Authors: Harry A. Quigley
Journal: New England Journal of Medicine (1993)

Our understanding of glaucoma has undergone dramatic changes in the past decade. The ferment has derived from new epidemiologic information, improved diagnostic methods, and developments in surgical and drug therapy. This review concentrates on primary open-angle glaucoma, the most prevalent form of the disorder in Western countries.DefinitionPrimary open-angle glaucoma usually affects both eyes and combines a particular abnormal appearance of the optic disk (optic-nerve head) with a slowly progressive loss of visual sensitivity (Figure 1). The characteristic appearance of the glaucomatous optic disk is visible by ophthalmoscopy (Figure 2). The present standard for determining visual loss in glaucoma . . .
Abstract 72: Gene-specific H3K4 trimethylation changes in healthy human subjects exposed to carcinogenic metal components of air particles
Authors: Laura Cantone, Thomas Kluz, Letizia Tarantini, Matteo Bonzini, Barbara Marinelli, Pier Alberto Bertazzi, Andrea Baccarelli, Max Costa
Journal: Cancer Research (2011)

Abstract Ambient and occupational exposure to air particulate matter (PM) has been consistently associated with increased risk of lung cancer. Epidemiological studies strongly indicate that the metal components of PM may be responsible for PM carcinogenicity, but the underlining mechanisms are poorly understood. H3K4 trimethylation (H3K4me3) is known to be modified by exposure to carcinogenic metals in-vitro and correlates with transcriptional activation when found in gene promoter regions. In a pilot study on workers of a steel-plant production, we investigated whether PM metal components, such as nickel and arsenic, had an effect on H3K4me3 in the promoter regions of target genes, including tumor suppressors and genes whose expression is increased following metal exposures, such as NIMA-related kinase 6 (NEK6) genes and carbonic anhydrase IX (CA9). We obtained blood samples on the first (sample 1) and last (sample 2) day of a working-week from 10 subjects. We used gene-specific analysis by chromatin immunoprecipitation (ChIP)-real-time PCR in blood leukocytes to investigate whether H3K4 trimethylation changes, at different levels of exposure to airborne metals in PM, can influence transcription of CA9 and NEK6 genes. We found that both for CA9 and NEK6, there was a difference between sample 1 and sample 2 in all subjects, with a higher level in sample 2; furthermore, in sample 2, we found a positive trend for H3K4me3 in CA9 and NEK6 genes with increasing levels of exposure to metals in PM compared to one unexposed control. The observed tendency is consistent with the fact that carcinogenic metals alter patterns of gene expression leading to activation of genes that may be relevant to the carcinogenic process. These findings indicate that different levels of exposure to PM metal components can induce changes in H3K4 trimethylation that up-regulates transcription of CA9 and NEK6 genes. 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 72. doi:10.1158/1538-7445.AM2011-72
AB0633 Association of Decrease Diffusing Lung Capacity with Progression Pulmonary Alterations by HRCT in Patients with Systemic Sclerosis over A Five-Year Period:
Authors: O.B. Ovsyannikova, O. Koneva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Functional lung tests play a one of the key role in assessment of SS pulmonary manifestations. As many as 90% of pts will have interstitial abnormalities on HRCT and 40-75% will have changes in pulmonary function tests (PFTs). <h3>Objectives</h3> to evaluate association of pulmonary function with differences interstitial abnormalities on high-resolution computed tomography (HRCT) in patients with systemic sclerosis over a five-year period. <h3>Methods</h3> It was a longitudinal study involving 83 pts with SSc (mean age was 46,2±13,4; 69% were limited; 95% were female). They were included from cohort of 150 pts. all fulfilling of ACR criteria of SSc and were evaluated in our department between 2006 and 2012yy (the mean duration of follow up was 58,9±12,0 months). The criteria of selected was consequently 5 years of follow up by PFTs and HRCT of lung. The pts were divided into two groups using of clinically significant DLCO reduction (at ≥10%) group 1 (n=31) and other without reduction - group 2 (n=52). Approximately five years after the first evaluation, the pts underwent spirometry and measurement of DLCO, chest HRCT, echocardiography. All pts received glucocorticoids, cyclophosphamide 42% (group 1) and 27% (group 2) (p&gt;0,05). <h3>Results</h3> the main characteristics were not significantly different between groups 1 and 2 (age 40.7±13.6 vs 37±13,3; duration of disease from the first non-Raynaud9s syndrome was 5,8±4,9 vs 8,4±7,6, presents of diffuse 39% vs 27% accordingly) (p&gt;0,05). SPAP remained within the normal range in both groups during 5 yrs (27.5±3.9 vs 31.5±8.9 and 29.4±7.0 vs 30.1±8.0 accordingly (p&gt;0,05)). The presents of a-Scl-70 was prevalence in group 1 than in group 2 (69% vs 46% (p&lt;0,05) RO 2,61 (0,99-6,84)). At the beginning DLCO was higher in the group 1, but after the 5 years follow up it became lower than in group 2. The comparison of PFTs and dates HRCT showed that clinically significant reduction of DLCO associated with worse of lung by HRCT. The number of pts with honeycombing in this group increased 18%, that significantly higher than in group without reduction of DLCO. <h3>Conclusions</h3> Chances of developing of honeycombing and worse of lung by HRCT higher in pts with clinically significant reduction of DLCO, instead of normal dates FVC. DLCO is the most significant marker of poor prognosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5169
Cost-Effectiveness Studies Aim to Tame Expenses, Probe Results
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Cost-Effectiveness Studies Aim to Tame Expenses, Probe Results Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 6, 16 March 1994, Pages 414–417, https://doi.org/10.1093/jnci/86.6.414 Published: 16 March 1994
Carcinoma of the Lung
Authors: Victor H. Kaunitz
Journal: New England Journal of Medicine (1950)

IN a suspected case of carcinoma of the lung, after x-ray examination, the first diagnostic tool that is usually employed is bronchoscopy. After a negative bronchoscopic report, the physician too often dismisses carcinoma as a diagnosis. A careful survey of the literature on thoracic surgery should serve to correct this assumption, and should focus attention on the limited value of bronchoscopy in diagnosis. It will also perhaps provide an idea of the prognostic significance of the negative bronchoscopic finding.With the more frequent use of bronchoscopy, and the apparent increase in the incidence of bronchogenic carcinoma, the incidence of positive . . .
SP0102 Practical Skills Session Entitled “ABCS of Biopsies: When to Perform and how to Interpret: Labial Salivary Gland Biopsy
Authors: A. A. Kruize
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The diagnostic process for conditions in which an inflammatory rheumatologic and/or connective tissue disease (CTD) is suspected consists primarily of history taking and physical examination. These two activities give the most important information leading to a differential diagnosis. Additional investigations can be helpful to confirm a tentative diagnosis, rule out other diagnoses or lead to other manifestations in (but also without) relation to the presumptive disease. Before requesting additional investigation(s) one should realize that these investigations should meet with the following conditions: it should give additive information to the information available from history taking and physical examination, it should be discriminative and the outcome should have therapeutic consequences. Participation in studies on clinical or translational scientific issues may also require additional investigations to complete classification and/or inclusion criteria. Indications of labial salivary gland biopsy are confirmation of a presumptive diagnosis of Sjögren's syndrome and other conditions causing dryness and/or salivary gland enlargement including sarcoidosis. PrimarySjögren's syndrome (pSS) is a slowly progressive autoimmune disorder, affecting mainly the exocrine glands, resulting in mucosal dryness of eyes, mouth, and vagina. PSS is a clinical diagnosis which may be confirmed by salivary gland biopsy, which is to be performed easily by clinicians including rheumatologists. The procedure is widely considered and used as the single most specific test for confirming a diagnosis of pSS. Main histopathological findings in salivary glands in pSS are focal sialo-adenitis with a focus-score ≥1 (focus: aggregate of &gt; 50 lymphocytes and histiocytes per 4 mm²) and an increase of IgG and IgM containing plasma cells. Technical procedures will be elucidated. Limitations including histological changes in salivary gland tissue being not 100% specific, focal sialo-adenitis not being pathognomic for pSS, will be discussed. Complications including persistent hypoesthesia of the lower lip region, when a nerve, in spite of the procedure of which all details can be followed by sight, is damaged, will be shared. <h3>Key messages to share</h3> How to use labial salivary gland biopsy in diagnosis and classification of pSS. Labial salivary gland biopsy is to be performed easily by a rheumatologist. <h3>Disclosure of Interest</h3> None Declared
Abstract 3593: Genetic variants in NER pathway genes and ovarian cancer risk and outcomes
Authors: Yilei Gong, Jie Lin, Yuanqing Ye, Lei Wu, Xia Pu, Xifeng Wu, Dong Liang, Karen Lu
Journal: Cancer Research (2010)

Abstract Nucleotide excision repair (NER) pathway is critical for protecting against damage from carcinogens. In this case-control study, we evaluated the associations between genetic variations in NER pathway and ovarian cancer risk in 339 Caucasian ovarian cancer cases and 349 Caucasian healthy controls. A comprehensive panel of 217 SNPs in 28 NER pathway genes was analyzed to assess their association with ovarian cancer risk. For the cases who received surgery and platinum-based chemotherapy, we also analyzed the association of these SNPs with overall survival and response to chemotherapy. Individually, 12 SNPs were significantly associated with the ovarian cancer risk. The most significant association was observed for SNP rs4150667 from GTF2H1 (OR = 0.64, 95% CI 0.47- 0.86). A strong gene-dosage effect was observed when these top 12 SNPs were combined for unfavorable genotype analysis. Compared to subjects carrying ≤ 2 unfavorable genotypes, individuals carrying 3 (OR = 2.11, 95% CI = 1.32−3.39), 4 (OR = 2.32, 95% CI = 1.47 − 3.66) or ≥ 5 (OR = 4.31, 95% CI = 2.75 − 6.78) unfavorable genotypes exhibited significantly increased risk for ovarian cancer (P for trend &amp;lt; 0.0001). Classification and regression tree (CART) analysis further revealed potential high order gene-gene interaction among the top 12 SNPs and identified 7 terminal nodes with the percentage of ovarian cancer cases in each terminal node range from 27% to 64%. In the clinical outcome study, there were 10 SNPs that exhibited significant association with overall survival. The unfavorable genotype analysis showed the median survival times for individuals carrying ≤3, 4∼7, and ≥ 8 unfavorable genotypes were 83.3, 40.0, and 24.7 months, respectively, indicating a strong gene-dosage effect (P for trend &amp;lt; 0.0001). We also observed significant gene-dosage effect in chemotherapy response. In summary, this pathway-based approach demonstrated that increasing numbers of unfavorable genotypes in the NER predispose susceptible individuals to increased risk of ovarian cancer and affect clinical outcomes in ovarian cancer patients. These findings warrant further replications in independent populations. 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 3593.