tbuckley/cabot-search huggingface dataset:
Abstract LB-384: <i>BARX1</i>, <i>CYGB</i>, and other epigenetic targets of gastric cancer
Authors: Rachana Agarwal, Yuriko Mori, Yulan Cheng, John M. Abraham, Elizabeth Montgomery, Stephen J. Meltzer
Journal: Cancer Research (2012)

Abstract Gastric cancer (GC), a disease with a very poor prognosis, is the second leading cause of cancer-related deaths worldwide. Although few studies have identified genetic and epigenetic alterations to be involved in gastric carcinogenesis, the molecular pathogenesis of this disease remains incompletely understood, and largely unexplored. With an aim to understand, and identify the molecular pathways important in the pathogenesis of GC, and to identify targets for its detection and therapy, we conducted a pilot microarray-based genome-wide search for identification of epigenetic targets in GC. This study identified 11 prioritized targets of aberrant epigenetic inactivation in gastric neoplasia (GN), including the tight junction protein claudin-11 (CLDN11), the transcription factor BarH-like homeobox (BARX1), basonuclin1 (BNC1), Coagulation factor C homolog (COCH), filamin C gamma (FLNC), cytoglobin B (CYGB), glutamine-fructose-6-phospahe-transaminase-2 (GFPT2), heat-shock-70 kDa protein-6 (HSPA6), snail homolog 1(SNAL1), skin calmodulin-related factor (SCARF), and tumor protein p53 binding protein 2 (TP53BP2). Our initial validations of these targets, particularly, CLDN11, BARX1 and CYGB confirmed these genes to be hypermethylated in their promoter region in gastric cancer cell lines and patient specimens, and their mRNA expression levels to be reduced in gastric cancer tissues and cell lines. More interestingly, our recent preliminary studies demonstrate that overexpression of the BARX1, in GC cells which lack its endogenous expression led to dramatic phenotypic changes in these transfected cells. Moreover, viable cell count was reduced in BARX1 transfected cells. BARX1 is a transcription factor which is known to be involved in the differentiation of embryonic endoderm into stomach. This study for the first time, identifies a potential role of BARX1 in gastric carcinogenesis. Further, large-scale validation studies are underway to confirm the role of BARX1 and other genes as potential targets for GC detection and therapy. 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-384. doi:1538-7445.AM2012-LB-384
Hematuria after endoscopic ultrasound-guided fine needle aspiration of a renal tumor in von Hippel-Lindau disease
Authors: S. Lakhtakia, E. Wee, R. Gupta, S. Anuradha, R. Kalpala, A. Monga, S. Arjunan, D. Reddy
Journal: Endoscopy (2012)

A 35-year-old man presented at our hospital with weight loss and diarrhea. Computed tomography (CT) enteroclysis was carried out for evaluation of the small bowel to investigate the diarrhea. The scan revealed bilateral renal cysts with complex renal masses, as well as multiple pancreatic cysts and a mass in the genu ([Fig. 1]). The patient was suspected as having von Hippel–Lindau (VHL) disease, which was confirmed after a CT brain revealed a cerebellar hemangioblastoma.
SAT0184 Ct Scan Confirms Presence of Erosion in Systemic Lupus Erythematosous and Primary Sjogren's Syndrome as Well as Healthy Control, with Different Characteristics as Compared to Rheumatoid Arthritis: an Observational Study of 90 Subjects:
Authors: F. Gandjbakhch, V. Foltz, J. Renoux, N. Cozic, N. Costedoat, D. Sene, G. Mercy, Z. Amoura, J.-C. Piette, N. Morel, P. Bourgeois, B. Fautrel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recent studies showed that MRI erosion may occur in Systemic Lupus Erythematosous (SLE) and primary Sjogren9s syndrome (pSS)<sup>12</sup>. TDM is considered as gold standard for bone evaluation. <h3>Objectives</h3> To describe TDM characteristics for the detection of erosion in patients with SLE and pSS without association with rheumatoid arthritis (RA) compared to "positive control", i.e. RA and "negative control" (sex/age-matched healthy controls). <h3>Methods</h3> pSS, SLE, RA patients and HC were prospectively included from 2 university departments (rheumatology and internal medicine) between 2009 and 2011. Inclusion criteria were: 1. For lupus and primary SS: disease duration &gt;2 years, no association with RA (i.e. no arthritis, no ACPA, normal X rays of hand and feet). 2. For healthy controls (HC): no history of tender or swollen joint or rheumatic disease. 3. For RA: established disease with duration &gt;2 years. CT scan and MRI of MCP2 to 5 and wrist of the dominant hand was performed in coronal and axial plans. Adaptation of the OMERACT definition for erosion was used in order to differenciate physiological cortical break,i.e. vascular foramen and erosion due to destructive disease. CT scan and MRI were evaluated according to RAMRIS by 2 independent readers, blindly to clinical and radiographic data. <h3>Results</h3> 90 subjects were included prospectively in the study: 19 primary SS, 21 Lupus, 32 RA and 20 HC.Patients characteristics were previously described<sup>1</sup>. 83% of RA patients were erosive on X-rays. All SLE/pSS patients had normal Xrays of hand and feet (inclusion criteria). Good correlation was observed between MRI and CT scans (Pearson coefficient 0.77, p&lt;0.0001; intraclass correlation coefficient (icc): 0.74). On CT scan, almost all patients and HC had at least one cortical break seen in 2 plans without statistical difference between the groups. Frequencies of patients having at least one erosion and mean number of erosions were statistically different between RA and SLE/pSS, while no statistical difference was seen between SLE/pSS and HC. RAMRIS<sub>erosion</sub> was higher in RA and statistically different from non-RA patients (Table). Erosions were most frequently observed in wrists with higher frequency in RA. <h3>Conclusions</h3> CT scan of hands/wrist correlates well with MRI and confirms presence of erosions different from vascular foramen in SLE/pSS as well as in HC. Erosions in SLE/pSS are similar with HC and differ from erosions seen in RA. <h3>References</h3> Gandjbakhch et al. EULAR 2013-OP0175. Boutry et al. Radiology. 2005 Aug;236(2):593-600. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5655
Abstract 370: Malignant Hyperthermia Mutation of RyR1 (Y522S) Increases Catecholamine-Induced Cardiac Arrhythmia Through Mitochondrial Injury
Authors: Jin O-Uchi, George A Porter, Sung Hyun Kang, Simona Boncompagni, Niina Sokolova, Polina Gross, Bong Sook Jhun, Gisela Beutner, Paul Brookes, Burns C Blaxall, Robert T Dirksen, Feliciano Protasi, Shi Pan, Shey-Shing Sheu
Journal: Circulation Research (2012)

Introduction: Mutations in skeletal muscle type ryanodine receptor (RyR1) exhibit life-treating human disorders including malignant hyperthermia (MH) and central core disease, which features skeletal muscle rigidity triggered by anesthesia and body temperature elevation. However, cardiac arrhythmias and/or sudden cardiac death in these patients are also frequently reported during anesthesia or even under the conscious condition. Hypothesis: Chronic mitochondrial Ca 2+ overload through leaky mutant RyR1 expressed at cardiac mitochondria leads to mitochondria injury and cardiac arrhythmia. Methods: We determined the cardiac phenotype of knock-in mice carrying a leaky RyR1 MH mutation Y522S (YS). Results: WT- and YS - RyR1 were expressed at mitochondria but not at SR in heart. Ultra-structure of heterozygous YS hearts exhibited severe abnormal/disrupted mitochondrial morphology as well as myofibril contractures (Fig. A-E). YS cardiac mitochondria showed high susceptibility to Ca 2+ -induced opening of mitochondrial permeability transition pores and depolarized mitochondrial membrane potential compared to WT, suggesting compromised mitochondrial functions. Langendorff perfusion developed similar LV pressure in response to high dose bolus of Isoproterenol in WT and YS, but only YS heart frequently developed multiple ventricular extrasystoles after Isoproterenol (Fig. F). Conclusion: Chronic mitochondrial damage by Ca 2+ overload through leaky mutant RyR1 induces mitochondrial structural and functional disruption, which facilitates arrhythmogenic outbursts under acute catecholaminergic stress.
Improved Treatment of Pancreatic Cancer by IL-12 and B7.1 Costimulation: Antitumor Efficacy and Immunoregulation in a Nonimmunogenic Tumor Model
Authors: Brigitte M. Pützer, Florian Rödicker, Mary M. Hitt, Thorsten Stiewe, Helmut Esche
Journal: Molecular Therapy (2002)

Ductal pancreatic adenocarcinoma is one of the commonest and most lethal cancers in the Western world. Unfortunately, recent advances in diagnostics, staging, and therapy in pancreatic carcinoma have not resulted in significant improvements in long-term survival. We have previously shown that adenovirus (Ad)-mediated coexpression of interleukin-12 (IL-12) and the costimulatory molecule B7.1 is extremely efficient in inducing regression of highly immunogenic transplanted and nontransplanted tumors. Here, we examined the antitumor efficacy of IL-12- and B7.1-based immunotherapy against a nonimmunogenic murine model of ductal pancreatic cancer. Compared with AdIL-12 treatment alone, single intratumoral injection of AdIL-12/B7.1 led to a prolonged immune response and mediated complete regression in 80% of treated animals. After rechallenge with parental tumor cells, 70% of cured mice remained tumor-free, suggesting that protective immunity had been induced. The antitumoral response was associated with upregulation of H-2K(b) and Abcb2 expression, whereas other components of the proteasome (Abcb3, Psmb9, and Psmb8) were not affected. These data indicate that upregulation of the antigen presentation machinery by AdIL-12/B7.1 may be a therapeutic rationale for nonimmunogenic, therapy-resistant pancreatic cancer.
Physical Fitness as a Predictor of Mortality among Healthy, Middle-Aged Norwegian Men
Authors: Leiv Sandvik, Jan Erikssen, Erik Thaulow, Gunnar Erikssen, Reidar Mundal, Kaare Rodahl
Journal: New England Journal of Medicine (1993)

Despite many studies suggesting that poor physical fitness is an independent risk factor for death from cardiovascular causes, the matter has remained controversial. We studied this question in a 16-year follow-up investigation of Norwegian men that began in 1972.Our study included 1960 healthy men 40 to 59 years of age (84 percent of those invited to participate). Conventional coronary risk factors and physical fitness were assessed at base line, with physical fitness measured as the total work performed on a bicycle ergometer during a symptom-limited exercise-tolerance test.After an average follow-up time of 16 years, 271 men had died, 53 percent of them from cardiovascular disease. The relative risk of death from any cause in fitness quartile 4 (highest) as compared with quartile 1 (lowest) was 0.54 (95 percent confidence interval, 0.32 to 0.89; P = 0.015) after adjustment for age, smoking status, serum lipids, blood pressure, resting heart rate, vital capacity, body-mass index, level of physical activity, and glucose tolerance. Total mortality was similar among the subjects in fitness quartiles 1, 2, and 3 when the data were adjusted for these same variables. The adjusted relative risk of death from cardiovascular causes in fitness quartile 4 as compared with quartile 1 was 0.41 (95 percent confidence interval, 0.20 to 0.84; P = 0.013). The corresponding relative risks for quartiles 3 and 2 (as compared with quartile 1) were 0.45 (95 percent confidence interval, 0.22 to 0.92; P = 0.026) and 0.59 (95 percent confidence interval, 0.28 to 1.22; P = 0.15), respectively.Physical fitness appears to be a graded, independent, long-term predictor of mortality from cardiovascular causes in healthy, middle-aged men. A high level of fitness was also associated with lower mortality from any cause.
Abstract 2899: Significance of microRNA:target interaction in bladder cancer metastasis.
Authors: Yuanbin Ru, Katerina J. Kechris, Steven C. Smith, George A. Calin, Dan Theodorescu
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through base pairing with other mRNA transcripts. MiRNA expression signatures have characterized many phenotypes in bladder cancer, including grade, stage, and metastasis. However, simultaneous mRNA changes accompanying the miRNA profile, along with the miRNA:mRNA interaction, have not been systematically studied in these phenotypes. To gain insights into the miRNA regulatory network in bladder cancer metastasis, we profiled miRNA and mRNA expression in two pairs of metastatic and non-metastatic cell lines. Interactions between differentially expressed miRNAs and mRNAs were predicted using 6 software programs. The candidate miRNA:mRNA pairs were further selected by their clinical relevance, including their expression in grade, stage, and tumor in 2 cohorts totaling 256 human tumors. We identified more miRNA:mRNA pairs with up-regulated miRNAs and down-regulated genes in metastatic cells than the pairs with down-regulated miRNAs and up-regulated target genes. The novel overexpression of one of the miRNAs, hsa-miR-146a, was confirmed by quantitative RT-PCR in metastatic cell lines. It has been shown that decreased level of hsa-miR-146a is associated with progression of prostate cancer and polymorphism in hsa-miR-146a gene is associated with prostate cancer risk. We are carrying out in vitro and in vivo experiments on the top 5 scoring pairs ranked by the number of prediction software and clinical relevance. Our results suggest the significance of miRNA regulatory network in cancer metastasis and provide a list of potential miRNA:mRNA pairs for further investigation. Citation Format: Yuanbin Ru, Katerina J. Kechris, Steven C. Smith, George A. Calin, Dan Theodorescu. Significance of microRNA:target interaction in bladder cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2899. doi:10.1158/1538-7445.AM2013-2899
AB1449-HPR The OA patient in primary healthcare, an observational study of communication and treatment based on discharge reports
Authors: G. Grønhaug, K.M.L. Grønhaug
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is well documented that early interventions of conservative treatment, including training, of OA of the knee are beneficial. It is further stated that communication among levels of the health services is beneficial due to outcome of treatment. Still it seems that these recommendations are not met in the day to day clinical practice in OA rehabilitation. <h3>Objectives</h3> To asses how communication is conducted between one orthopedic surgeon and local physiotherapists regarding newly diagnosed patients with OA of the knee and to asses the treatment given by the physiotherapists. <h3>Methods</h3> 18 newly diagnosed patients with OA of the knee who was remitted to physiotherapy were identified. All patients was remitted by the same orthopedic surgeon. A letter was sent to the patients asking what local physiotherapist they had been consulting. After receiving 15 answers from the patients a second letter was sent to the physiotherapists asking for discharge reports regarding the patients identified and used in this study. Treatment given by the physiotherapists were identified from the received discharge reports and divided in: Cardiovascular training, strength training, local endurance, mix of local endurance and strengthening exercises and unknown/not possible to perceive from the discharge report. <h3>Results</h3> The orthopedic surgeon had not received any discharge reports from any of the physiotherapists by the start of the study. We received 9 (75%) discharge reports after the first letter, and 3 more after a follow up letter (80%). It was conducted 221 treatments on 11 patients (for 1 of the patients the number of treatments are unknown). 7 (58%) had received local endurance, 3 (25%) had received a mix of local endurance and strengthening exercises, 2 (17%) the treatment is unknown. None of the discharge reports contained any objective parameters of evaluation regarding initial status or progression of the patients. <h3>Conclusions</h3> Although the compliance in this study is high (80%) there seems to be a lack of communication between professions and levels of health care. None of the physiotherapists had sent discharge reports initially although this is supposed to be sent routinely. Although the initial diagnosis was the same the treatment given varies widely. It seems to be a need for further initiatives regarding communication between professions and levels of health care to ensure predictable, evidence based treatment of OA of the knee. Further research with a larger sample size is needed to confirm these findings. <h3>Disclosure of Interest</h3> None Declared
Abstract 4808: Discovery of a phospho-signature predicting response to dasatinib in non-small cell lung cancer
Authors: Martin Klammer, Marc Kaminski, Alexandra Zedler, Felix Oppermann, Stefan Müller, Andreas Tebbe, Mark Whittaker, Klaus Godl, Christoph Schaab
Journal: Cancer Research (2012)

Abstract Since targeted drugs selectively block molecular pathways that are typically over-activated in tumour cells, they are more precise and show fewer adverse effects than traditional chemotherapeutic agents. At the same time the proportion of patients that benefit from targeted drugs is smaller. Therefore, predictive molecular markers are needed to confidently predict the patient's response to a specific therapy. Such markers would facilitate therapy personalization, where the selected therapy is based on the molecular profile of the patient. We sought to identify a signature of protein phosphorylations that predicts the response to dasatinb in non-small cell lung cancer cell lines. A panel of cell lines were profiled in a global, unbiased, phosphoproteomics study yielding quantitative information for roughly 25,000 phosphorylation sites. The identical cell lines were tested for their response to dasatinib. From the phosphoproteome profiles, we identified a signature of twelve phosphorylation sites that can accurately predict dasatinib sensitivity. Four of the phosphorylation sites belong to integrin α4, a protein that mediates cell-matrix or cell-cell adhesion. We evaluated the performance of this signature in a cross-validation set-up and investigated the robustness of the selected predictive features. Finally, we confirmed the predictive power of the signature in an independent set of breast cancer cell lines. We showed that the phosphorylations of integrin β4 as well as eight further proteins are candidate biomarkers for predicting response to dasatinib in solid tumours. Furthermore, we demonstrated that identifying predictive phosphorylation signatures from global, quantitative phosphoproteomic data is possible, and opens a new path to discovering molecular markers for response prediction. 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 4808. doi:1538-7445.AM2012-4808
AB0694 The efficacy and safety of abatacept (orencia) in patients with active juvenile idiopathic arthritis (jia).
Authors: E. S. Zholobova, O. U. Konopelko, O. S. Rozvadovskaya, M. N. Nikolaeva, V. Y. Eljashevich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> From 2009 Abatacept (ABA) – a new generation biological DMARD was approved in Russia. ABA selectively modulates T-cell activation, which seems to play the key role in the pathogenesys of JIA. Efficacy and safety of ABA was assessed in AWAIKEN trial in different types of patients who had polyarticular course of JIA at the enrollment. This prospective observation was aimed to assess effectiveness and safety of ABA in patients with different types and clinical variants of active JIA in real clinical practice. <h3>Methods</h3> 27 children with JIA were treated with ABA. 20 (74%) pts had polyarticular course of JIA and 7 (26%) - systemic JIA. 25 (93%) of pts were female. All patients had high degree (III) of disease activity. Mean disease duration was 5,9 ± 3,3yr. 26 patients previously had an inadequate response to 2 or more non-biological, one child with heavy course of systemic JIA was treated with infliximab during 1 year before starting ABA. Treatment effectiveness was assessed according to the ACR Pediatric criteria: ACR pedi 30, ACR pedi 50, ACRpedi 70, and ACR pedi 90 after 6 and 12 months of abatacept therapy. All patients received ABA in dose 10 mg/kg at day 1, week 2 and 4 and every 4 weeks thereafter. <h3>Results</h3> In the group of pts with systemic JIA after 6 months of ABA treatment 6 of 7 patients (86%) achieved ACR Pedi 30 response, 5 (71%) – ACR Pedi 50, and 3 (43%) – ACR Pedi 70. 12 months data was available for 5 patients (others are still on treatment but less than 12 moths). Four of five pts (80%) achieved ACR pedi-30, 3(60%) - ACR Pedi 50 response, 2 (40%) ACR pedi 70, and 1 (20%) ACR pedi 90. In the group of pts with poliarticular course of JIA treatment effectiveness was assessed in 19 pts. One girl had experienced an infusion-related reaction (potentially associated with hypersensitivity) after 3<sup>rd</sup> infusion and ABA treatment was stopped. After 6 months 17 of 19 pts (89%) achieved ACR pedi 30 response, 14 (74%) - ACR pedi-50, 6 (32%) - ACR pedi-70, 2 (11%) - ACR pedi 90. 11 of 20 patients with polyarticular JIA have completed 12 months of ABA treatment. 9 of them (82%) achieved ACR pedi 30 response, 8 (73%) - ACR pedi 50, 5 (45,0%) - ACR pedi 70 and 1 (9%) - ACR pedi 90. Adverse events were observed in 2 patients (7,4%): 1 case of infusion related reaction, 1 pts experienced common Herpes simplex infection (ABA treatment was stopped after 12 months). <h3>Conclusions</h3> Abatacept have shown its effectiveness in the majority of patients with long standing JIA (systemic and polyarticular course) with high disease activity, and inadequate response to previous treatment with DMARDs. Better results were observed in patients with poliarticular JIA. <h3>Disclosure of Interest</h3> None Declared
P845 IMPACT OF FAT VERSUS GLUCOSE LOAD ON OXIDATIVE STRESS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: C. Rosso, E. Vanni, L. Mezzabotta, R. Gambino, F. Saba, S. Carenzi, A. Gastaldelli, M. Gaggini, E. Buzzigoli, C. Saponaro, F. Carli, G.P. Caviglia, M.L. Abate, F. Salomone, A. Smedile, M. Rizzetto, M. Cassader, E. Bugianesi
Journal: Journal of Hepatology (2014)