tbuckley/cabot-search huggingface dataset:
FRI0195 Somatic Comorbidities and Comorbid Depression Are Associated with Mortality among Patients with Rheumatoid Arthritis: A 14-Year Prospective Cohort Study
Authors: J. Van Den Hoek, H.C. Boshuizen, L.D. Roorda, G.J. Tijhuis, M.T. Nurmohamed, J. Dekker, G.A. van den Bos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>OBJECTIVES</h3> At least three clinically indistinguishable but genetically different types of autosomal dominant pure spastic paraplegia (ADPSP) have been described. In this study the clinical, genetic, neurophysiological, and MRI characteristics of ADPSP were investigated. <h3>METHODS</h3> Sixty three at risk members from five families were clinically evaluated. A diagnostic index was constructed for the study. Microsatellite genotypes were determined for chromosomes 2p, 14q, and 15q markers and multipoint linkage analyses were performed. Central motor conduction time studies (CMCT), somatosensory evoked potential (SSEP) measurement, and MRI of the brain and the total spinal cord were carried out in 16 patients from four families. <h3>RESULTS</h3> The clinical core features of ADPSP were homogeneously expressed in all patients but some features were only found in some families and not in all the patients within the family. In two families non-progressive "congenital" ADPSP was seen in some affected members whereas adult onset progressive ADPSP was present in other affected family members. As a late symptom not previously described low backache was reported by 47%. Age at onset varied widely and there was a tendency for it to decline in successive generations in the families, suggesting anticipation. Genetic linkage analysis confined the ADPSP locus to chromosome 2p21-p24 in the five families. The lod scores obtained by multipoint linkage analysis were positive with a combined maximum lod score of Z=8.60. The neurophysiological studies only showed minor and insignificant prolongation of the central motor conduction time and further that peripheral conduction and integrity of the dorsal columns were mostly normal. Brain and the total spinal cord MRI did not disclose any significant abnormalities compared with controls. <h3>CONCLUSIONS</h3> ADPSP linked to chromosome 2p21-p24 is a phenotypic heterogeneous disorder characterised by both interfamilial and intrafamilial variation. In some families the disease may be "pure" but the existence of "pure plus" families is suggested in others. The neurophysiological and neuroimaging investigations did not show any major abnormalities.
A2.35 Glatiramer acetate restores the defective activity of regulatory B cells in SLE
Authors: K Amrouche, JO Pers, S Hillion, C Jamin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Glatiramer Acetate (GA) is a synthetic pol&nbsp;ypeptide used in treatments of multiple sclerosis. Numerous studies have been performed to understand its effects on immune cells, but its role on B cells has been hardly described. Treatment of experimental autoimmune encephalomyelitis mice with GA has been shown to increase the frequency of CD5<sup>+</sup>CD1dHigh B cells known to develop regulatory function. The possibility therefore exists that GA might activate regulatory B (Breg) cells. The aim of our work was to evaluate the ability of GA to stimulate the regulatory functions of B cells in healthy individuals and to appraise its effect on SLE Breg cells known to be defective. <h3>Materials and methods</h3> B cells were purified from SLE and healthy donors and stimulated for 4 h with GA. Autologous T cells were stimulated with anti-CD3 and anti-CD28 Abs. Their proliferation was evaluated by flow cytometry and the concomitant production of IFNgamma evaluated by ELISA. The regulatory activities of B cells on T cell responses were evaluated after 4 days in co-culture experiments. Phenotypical analyses by flow cytometry were performed using FITC-conjugated GA to identify the subsets of B cells able to catch the GA. <h3>Results</h3> The proliferative response and the IFNgamma production of T cells from healthy donors were significantly decreased in the presence of GA-stimulated B cells compared to non-stimulated B cells. Interestingly, the defective regulatory activity of non-stimulated SLE B cells on SLE T cells was restored after 4-hour stimulation with GA before co-cultures. Memory B cells bound high level of FITC-conjugated GA in contrast to naïve B cells. After sorting and stimulation with GA, increased-GA dependent regulatory activities were specifically triggered in memory B cells and not naïve B cells. <h3>Conclusions</h3> GA up-regulates the regulatory functions of B cells. These effects are mainly directed to the memory B cell pool. Specifically in SLE patients in which the Breg cells are defective and the memory B cell compartment abnormally elevated, our results suggest that GA treatment could restore the regulatory activity of the B cells and contribute to the efficacy of the GA-based therapeutics in autoimmune diseases.
In-111 Pentetreotide SPECT Imaging of Carcinoid Tumor of the Duodenum
Authors: B D Nguyen, B B Chin, D P Beall
Journal: Clinical Nuclear Medicine (1997)

The authors present a case of Zollinger-Ellison syndrome that was assessed by In-111 pentetreotide SPECT imaging. The detected gastrin producing tumor was a duodenal carcinoid located in the right upper quadrant of the abdomen.
Abstract 4988: <i>Cis</i>-acting genetic variation is associated with altered allele-specific expression of CEBPG transcript in normal human bronchial epithelium
Authors: Thomas M. Blomquist, Ron Brown, Erin L. Crawford, James C. Willey
Journal: Cancer Research (2010)

Abstract CEBPG (CCAAT/enhancer binding protein gamma) is one of six known members of the CEBP family of bZIP transcription factors. Gene targeted knock-out of CEBPG transcription factor in mice results in early perinatal death, presumably due to observed emphysematous lung histology and abnormal development of alveolar pneumocytes (Kaisho et al, 1999). In recent studies, we observed that: 1) CEBPG transcript expression in normal human bronchial epithelial cells (NBEC) varies greater than 20-fold among individuals (Mullins et al, 2005), 2) the pattern of CEBPG transcript expression in NBEC is different between lung cancer cases and controls (Blomquist et al, 2009), and 3) transcript expression of a key DNA repair gene, ERCC5 (XPG), is partly regulated by CEBPG in NBEC (Crawford et al, 2007). In this study we hypothesized that variation in CEBPG transcript expression patterns in NBEC may, in part, be due to cis-acting genetic variation. In order to test this hypothesis, Allele-Specific Expression (ASE) was measured at transcribed polymorphic site rs2772 in Exon 2 of CEBPG in NBEC cDNA of fifteen individuals heterozygous at rs2772 using allele-specific competitive PCR. ASE at rs2772 was then assessed for association with genotype at the seven polymorphic sites (rs736682, rs17530479, rs17530508, rs1469084, rs16968029, rs3745968, rs36101103) representing the most common haplotypes in the promoter, intron and 3′-untranslated regions of CEBPG gene. CEBPG rs2772 A allele was expressed, on average, 2.34 fold greater than C allele (p &amp;lt; 0.001) in 20% (3 out of 15) of NBEC cDNA samples, among individuals heterozygous at both rs2772 and rs17530479 in the 3′-untranslated and promoter regions of CEBPG, respectively. These findings are consistent with previous reports that in 20% of samples, CEBPG rs2772 A allele was expressed 2.42 fold greater than C allele (Lo et al, 2003). We also observed that 3 out of 9 NBEC samples obtained from individuals diagnosed with lung cancer exhibited rs2772 A:C allelic ratios significantly higher than genomic DNA controls, while 0 out 6 samples from individuals without lung cancer exhibited altered ASE. Of note, rs2772 and rs17530479 polymorphic sites are in linkage disequilibrium with rs10518275 polymorphic site, which was recently associated with severity of cystic fibrosis lung disease (Gu et al, 2009). Here we demonstrate that cis-acting variation in linkage with rs2772 and rs17530479 polymorphic sites is associated with variation in ASE of CEBPG and lung cancer diagnosis. 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 4988.
P12.04 * GLIOMATOSIS CEREBRI: IS THERE A ROLE FOR SURGERY OTHER THAN BIOPSY?
Authors: A. Agnoletti, L. Bertero, R. Fornaro, F. M. Calamo Specchia, D. Garbossa, M. Lanotte, P. Cassoni, R. Soffietti, R. Ruda, A. Ducati
Journal: Neuro-Oncology (2014)

INTRODUCTION: Gliomatosis cerebri (GC) is a highly infiltrative glial neoplastic lesion that involves at least three lobes (as defined by WHO 2007). GC can appear as primary GC or result from a spread of a focal glioma and it is usually an aggressive neoplasm corresponding to WHO grade III. Due to the tumor extension, patients are generally not candidate to surgical resection, but biopsy is performed in order to obtain an histological diagnosis. Prognosis remains limited despite treatment with chemotherapy and/or radiotherapy. MATERIALS AND METHODS: We retrospectively analysed patients with GC who underwent surgery at our Institution from 2001 to 2012. We focused on the type (biopsy vs partial resection) and the outcome of surgery at the time of diagnosis and the role of surgery at tumor progression. Diagnosis of GC in patients whose histological evaluation after surgery resulted not conclusive was defined by MR spectroscopy (MRS) and/or by IDH1 mutation immunohistochemistry. RESULTS: We collected a total of 38 patients with diagnosis of GC treated at our Institution. 24 out of 38 (63%) were males. Median age at diagnosis was 50.5 (range: 21-72), median KPS at diagnosis was 80 (range: 60-100). As for the MRI patterns at the time of diagnosis, contrast enhancement (CE) was absent in 21/38 (55%) and mild-patchy in 17/38 (45%). 25 patients out of 38 (66%) underwent biopsy only, 13/38 (34%) underwent partial resection. In the group of patients who underwent biopsy the median age at diagnosis was 52 (range: 21-72), median KPS at diagnosis was 80 (range: 60-90).Two patients had serious hemorrhage after biopsy. Histological diagnosis was conclusive in 22/25 (88%), while in three patients histological diagnosis was aspecific gliosis. Median overall survival (OS) in this group of patients was: 17 months (range: 7 months-10 years). 7 patients out of 25 (28%) are still alive. In the group of patients who underwent partial resection the median age at diagnosis was 50 (range: 25-66), median KPS at diagnosis was 80 (range: 70-100) and was unchanged after surgery. Histological diagnosis was conclusive in all patients (100%). Median OS was: 22 months (range: 4.5 months-9 years). Three patients out of 12 (25%) are still alive. Four patients underwent surgical resection of a symptomatic enhancing lesion at the time of tumor progression after treatments (chemotherapy and/or radiotherapy). In 2 patients KPS improved after surgery, while in the remaining patients KPS was stable. Median OS after second surgery was 6 months. One patient is still alive. CONCLUSIONS: Compared to biopsy alone, partial resection that provides more tissue to the neuropathologist, allows an increase of “conclusive” histological diagnosis. Type of surgery at diagnosis could impact the outcome. Second surgery can be an option at the time of tumor progression when patient develops a focal, enhancing, symptomatic mass.
Abstract 1470: Depletion of glycosphingolipids with MBO-asGCS eliminates cancer cell metastasis
Authors: Kaustubh N. Bhinge, Vineet Gupta, Yong Y. Liu
Journal: Cancer Research (2011)

Abstract Tumor metastasis, particularly multi-organ metastasis often causes failure of cancer treatment. It is well-known that the interaction of tumor cells with extracellular matrix (ECM) determines the metastatic ability of cancer cells; however, it is not clear whether depletion of glycosphingolipids (GSLs), a major component of GSL-enriched microdomain on plasma membrane is an approach to eliminate tumor metastasis. Glucosylceramide synthase (GCS) that converts ceramide to glucosylceramide is a limiting enzyme controlling GSL synthesis. We found that overexpression of GCS enhanced metastatic ability of human breast cancer cells. In MCF-7/Dox cells, GCS protein levels were increased 39 folds and GCS activity were increased 2 folds, as compared to MCF-7 cells. The wound healing, Matrigel attachment and MMP-9 activity in MCF-7/Dox cells increased 1.5 folds, 3 folds, and 2 folds respectively compared to MCF-7 cells. Introduction of GCS gene overexpressed GCS protein and significantly increased wound healing and Matrigel attachment by 2 folds and cell invasion 1.5 folds in MCF-7 cells. MBO-asGCS is a mixed backbone oligonucleotide that substantially suppresses GCS expression. Silencing of GCS with MBO-asGCS (100 nM) decreased the wound healing by 2 folds, Matrigel attachment by 1.5 folds and cell invasion by 3 folds in MCF/Dox cells. These results were also observed in MCF-7/DOX cells treated with d-PDMP, a GCS inhibitor. Mechanistic study indicated that overexpression of GCS increased GSLs, particular globo-series GSLs and enhanced VEGF and uPA to promote the mobility, cellular attachment and invasion of cancer cells. As GCS overexpression is tightly associated with drug-resistant cancer cells, this study may suggest that depletion of GSLs with MBO-asGCS is an effective approach to eliminate the metastasis of cancers that even fail in conventional chemotherapy. 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 1470. doi:10.1158/1538-7445.AM2011-1470
Aneurysm of the Abdominal Aorta and Iliac Arteries
Authors: Frank Wheelock, Robert S. Shaw
Journal: New England Journal of Medicine (1956)

ANY artery in the body has the potential of dilating abnormally if weakness develops in the artery wall. If this dilatation is of significant degree, the lesion is described as an aneurysm. If the weakness and dilatation involves most of the circumference of the vessel, the aneurysm is described as fusiform; if one wall gives more than the others, a saccular aneurysm develops on that side. In either type, growth increases the bursting force on the wall as well as thinning the wall; consequently, rupture is a frequent and disastrous complication.Aortic aneurysms have been recognized since the Middle Ages, . . .
Abstract 5222: Molecular imaging of GSK-3β and CK1α kinase activities in response to Wnt signaling
Authors: Shyam Nyati, Mahaveer Swaroop Bhojani, SwathiChitra Pasupulathi, Brian D. Ross, Alnawaz Rehemtulla
Journal: Cancer Research (2010)

Abstract The Wnt signaling pathway has been found to be disregulated in many carcinomas of gastrointestinal system. GSK-3β and CK1α act as molecular switch that dictates both on and off states of Wnt/beta-catenin signaling by regulating cellular levels of the Wnt effector molecule β-catenin. In the absence of the Wnt signal β-catenin is initially phosphorylated by CK1α at S45, followed by GSK-3β at S41, T37 and S33 which marks it for proteosomal degradation. Although GSK-3β is one of the key regulators of the Wnt signaling pathway, the ability for direct, non-invasive &amp; real-time measurement of its kinase activity has been unavailable. Here we describe a chimeric, gain of function, split luciferase based novel reporter for monitoring of dual kinase (GSK-3β and CK1α) activity. The N-terminal β-catenin peptide (aa 29-48) harboring phosphorylation sites for GSK-3β and CK1α was synthesized and used to construct bioluminescence β-catenin reporter (BCR). This reporter when expressed in SW620 colon carcinoma cells and treated with LiCl and small molecular inhibitors SB415286 (GSK-3β) and CKI-7 (CK1α), lead to a dose and time dependent increase in the bioluminescence which was validated by western blotting. Cell lines stably expressing mutant reporters exhibited attenuated response to LiCl &amp; SB415286 (S37A mutant) and to CKI-7 (S45A mutant) confirming specificity of the reporter. To quantify the Wnt dependent change in the activity of the reporters, stable cell lines were generated in HEK293 background which has an intact Wnt signaling pathway. The WT reporter cell line showed over two fold induction with Wnt conditioned media while S37A mutant reporter cell line did not show a significant change in reporter activity corroborating the specificity of the reporters. In mice bearing tumors expressing the wild-type reporter, treatment with LiCl resulted an initial increase in the bioluminescence activity at 4 h which peaked at 7 h. Subsequent imaging revealed oscillations of the bioluminescence activity with a frequency of 14 h and an amplitude that decreased with time. Our reporters provide a powerful, novel tool for sensitive, real time, dynamic, non-invasive monitoring of GSK-3β and CK1α kinase activities in-vitro and in-vivo and have the potential in executing novel therapeutic regimens targeting GSK-3β/CK1α. 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 5222.
Abstract 1066: Combination synergy of JAK inhibitor, BVB808, and FGFR inhibitor, BGJ398, in an FGFR3-driven multiple myeloma model
Authors: Maria Pinzon-Ortiz, Lujian Tan, Yao Yao, Robert Schlegel, Thomas Radimerski, Z. Alexander Cao
Journal: Cancer Research (2012)

Abstract Multiple myeloma is a genetically heterogenous malignancy. Several clinical studies have indicated that the t(4:14)(p16:q32) translocation is associated with poor clinical prognosis. Two key target genes in this translocation are FGFR3 and MMSET. Additionally, activating mutations of FGFR3 have been identified, further implicating the involvement of this target in multiple myeloma. Recent advances have shed more light on the interaction between tumor cells and their microenvironment. The bone marrow stroma, endothelial cells, osteoclasts and others could promote the proliferation, survival and resistance to therapies of the malignant plasma cells. IL-6 is one of the major cytokines implicated in the tumor microenvironment. IL-6 signaling, mediated through receptor-coupled JAK-STAT pathway, has been reported to play an important role in cancer cell survival. Here we examine the combination effects of JAK inhibitor BVB808 and FGFR inhibitor BGJ398 against multiple myeloma in the preclinical setting. Combination of BVB808 and BGJ398 was tested in vitro in a panel of multiple myeloma models across broad drug concentrations. Significant synergy is noted in OPM II, a cell line harboring both t(4:14) translocation and FGFR3 K650E mutation. This combination benefit is further confirmed in the xenograft model bearing OPM II. We propose 2 hypotheses for this combination effect: 1) FGFR3 and IL-6/JAK-STAT may represent 2 parallel survival pathways in MM. When one pathway is inhibited, tumor cells would rely on the other axis as the alternative survival pathway. Synergy is noted only when both pathways are inhibited. 2) JAK-STAT may cooperate with FGFR3 to promote its activity. Synergy is achieved when potent and sustained inhibition of FGFR3 signaling is achieved with the combination of BVB808 and BGJ398. While it is an intriguing finding, the combination benefit is not observed across other MM models harboring FGFR3 lesions. Elucidation of the underlying molecular mechanism would enable more targeted therapies against two important targets in multiple myeloma. 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 1066. doi:1538-7445.AM2012-1066
ENSAYO CLÍNICO COMPARANDO PROPOFOL VS PROPOFOL MAS MIDAZOLAM EN ENDOSCOPIA DIGESTIVA ALTA DIAGNÓSTICA: RESULTADOS PRELIMINARES
Authors: L Julián-Gómez, SJ Rodríguez-Gómez, A Fuentes-Coronel, C Ochoa-Sangrador, P Fradejas-Salazar, E Martín-Garrido, C López-Ramos, P Conde-Gacho, C Bailador-Andrés, A Pérez-Villoria
Journal: Endoscopy (2011)

Objetivos: Comparar la sedación en EDA con propofol vs. propofol y bajas dosis de midazolam, en términos de seguridad, eficacia, satisfacción del paciente y calidad endoscópica.
Abstract 648: Combined PI3K and MEK inhibition in patient-derived xenografts generated from recurrent triple negative breast cancer
Authors: Yasir H. Ibrahim, Violeta Serra, Maurizio Scaltriti, Ludmila Prudkin, Pilar Anton, José Perez, Judit Balmaña, José Baselga
Journal: Cancer Research (2011)

Abstract Both the PI3K and ERK pathways have become critical therapeutic targets due to their importance in breast cancer. Some triple negative breast cancers (TNBC) are sensitive to MEK inhibition due to the presence of RAS activation signatures. However, hyperactivation of PI3K signaling through PTEN loss impairs efficacy of MEK inhibitors in TNBC. On the other hand, it is likely that inhibition of PI3K in TNBC results in compensatory feedback activation of MEK, as previously observed in HER2 positive cell-line models. Therefore, combined inhibition of both PI3K and MEK would translate to optimal therapeutic efficacy in the clinic. We generated patient-derived xenografts (PDXs) of TNBC from patients with recurrent disease to assess the efficacy of this combined therapy in a model that more closely resembles the clinical scenario. Upon completion of informed patient consent, biopsies from patients with cutaneous, axillary or subclavicular metastases that had progressed from standard therapies were implanted in female nude mice. Five TBNC PDXs were expanded and confirmed to have equivalent pathological and morphological features as the original patient samples; they maintained similar ER, PR, HER2, PTEN and Ki67 status. Mutation status of PI3K, PTEN and RAS pathway were also evaluated. Additionally, the PTEN-loss transcriptional program and RAS-like transcriptional program were evaluated to further classify the tumors. PDXs were treated with a pan-class I PI3K inhibitor (NVP-BKM120) and a MEK inhibitor (AZD6244) as single agent or in combination. Preliminary tumor growth studies in a PDX that lacked PTEN expression demonstrated NVP-BKM120 sensitivity, but no response to AZD6244. The combination of NVP-BKM120 plus AZD6244 augmented the PI3K tumor inhibitory effect. Ongoing studies will more precisely delineate the relationship between pathway activation status and pharmacodynamic response to inhibitors targeting PI3K or MEK. These data highlight the great potential for evaluating new strategies in models that truly represent breast cancer of patients enrolling in clinical trials. In these studies we attained data from models that faithfully resemble the disease observed in the clinic supporting the advancement of clinical trials targeting both PI3K and Ras/Raf pathways in TNBC. Since these models strongly resemble the clinical disease, PDXs can also offer new opportunities to test experimental therapies that are normally hindered by the homogeneity and culture selection of standard cell-lines. 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 648. doi:10.1158/1538-7445.AM2011-648
896 INTERFERON-a TREATMENT DIFFERENTIALLY REGULATES THE EXPRESSION OF INTERFERON-INDUCIBLE GENES IN HIPPOCAMPAL AND PREFRONTAL CORTEX NEURONS
Authors: C. Hoyo-Becerra, A. Hübener, M. Trippler, L. Poggenpohl, G. Gerken, J. Schlaak
Journal: Journal of Hepatology (2012)