tbuckley/cabot-search huggingface dataset:
THU0340 Cytokines’ study in patients with different subtypes of juvenile idiopathic arthritis
Authors: Y. Boyko, V. Chernyshov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cytokines play a significant role in pathogenesis of different subtypes of Juvenile Idiopathic Arthritis (JIA). Cytokines’ profile investigation enables differentiation of these subtypes <h3>Objectives</h3> To investigate cytokines, their receptors and agonists in patients with different subtypes of JIA <h3>Methods</h3> Blood serum of 105 patients with active JIA was studied for IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17andIFN-γcytokine levels, as well as their receptors and agonists – IL-1Ra, sCD25, sIL6R, sTNFR1. Patients were classified into following subtypes, according to the disease course: systemic – 16 patients, oligoarthritis – 38, polyarthritis with negative rheumatoid factor -19, enthesitis-arthritis – 27, polyarticular arthritis with positive rheumatoid factor – 2 (not included in study), psoriatic arthritis – 3 (not included) <h3>Results</h3> In comparison with a control group, a statistically significant increase in TNF-α (p&lt;0,05), sTNF 1R (p&lt;0,001), IL-6 (p$&lt;&lt;$0,000001), IL-1Ra (p=0,01) levels was seen in patients with systemic JIA, together with a decrease in IL-10 level (p&lt;0,05). Cytokines’ analysis in patients with oligoarthritis revealed a significant increase in TNF-α (p&lt;0,005), sTNF 1R (p&lt;0,001), IL-6 (p&lt;0,001), IFN-γ (p&lt;0,05), IL-17 (p&lt;0,05), sCD25 (p&lt;0,05) levels, as well as a decrease in IL-10 level (p&lt;0,005). In comparison with control group, patients with polyarthritis with negative RF had a significant increase in TNF-α (p&lt;0,005), sTNF 1R (p&lt;0,001), IL-6 (p&lt;0,001), IFN-γ (p&lt;0,05), IL-17 (p&lt;0,05) and sCD25 (p&lt;0,05) levels, as well as a decrease in IL-10 level (p&lt;0,005). The group of patients with enthesitis-arthritis had a significant increase of TNF-α (p&lt;0,005), sTNF 1R (p&lt;0,005) cytokines levels, as well as a decrease in IL-10 level (p&lt;0,05) in comparison with healthy children group. In patients with systemic JIA, in comparison with patients with oligoarthritis, a significant increase in IL-6 (p&lt;0,00005) and IL-1Ra (p&lt;0,01) levels was seen, while in comparison with patients with polyarthritis – a significant increase in IL-6 (p&lt;0,001), IL-1Ra (p=0,05) levels, and in comparison with enthesitis-arthritis patients – an increase in IL-6 level (p&lt;0,00001) <h3>Conclusions</h3> Systemic JIA is a typical auto-inflammatory disease with increase in IL-6 andIL-1Ra levels, which discriminates it from the other JIA subtypes. In patients with polyarticular JIA an increase in pro-inflammatory cytokines IFNγ/IL-17andTNF-α as well as a decrease in IL-10was revealed, which, probably, reflects a disbalance between Th1/Th17 andTregCells. An increase of blood serum IL-17in patients with polyarticular JIA may be considered as biomarker of this JIA subtype <h3>Disclosure of Interest</h3> None Declared
The Antiproliferative Effect of Calcitriol on Breast Cancer Cell Lines Depends on Vitamin D Receptor Status and the Expression of Prostaglandin Metabolizing Enzymes.
Authors: M. Thill, H. Friedericke, K. Katharina, C. Dittmer, F. Dorothea, D. Klaus, F. Michael, S. Becker
Journal: Cancer Research (2009)

Abstract Background: Both first studies in prostate cancer and our results in breast cancer suggest a link between vitamin D and prostaglandin metabolism. There is a growing body of evidence that COX-2 expression is a fundamental step in breast cancer pathogenesis acting through prostaglandin-dependent and independent mechanisms. The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR), render the biologically active form of vitamin D a promising target in breast cancer therapy.Materials and methods: The expression of VDR, COX-2 and 15 PGDH was determined by Western blot in MCF-10F cells, a human benign epithelial cell line, in MCF-7 cells, a moderate invasive and in MDA-MB-231 cells, a highly invasive breast cancer cell line. Measurement of basal PGE2 secretion was performed with ELISA. The influence of calcitriol on cell proliferation was determined by 5-bromo-2-deoxyuridine (BrDU) incorporation (BrDU ELISA). In addition we examined the effect of calcitriol on COX-2, 15 PGDH and VDR protein levels compared to untreated cells.Results: After 72 hours the proliferation of MCF-10F cells was dose-dependent inhibited to 0.83± 0.1 by 1 nM calcitriol. Concurrently, we observed a reduction of COX-2 expression to 0.63± 0.05 as compared to the untreated control group, but we also found a reduction of 15 PGDH to 0.73± 0.16. These effects were associated with a higher expression of VDR to 1.64± 0.16. Interestingly, MCF-7 cell growth was reduced to 0.52± 0.04 by 10 nM calcitriol and to 0.7± 0.06 by 1 nM. These effects do not seem to be associated with COX-2 and 15 PGDH and are independently of VDR. VDR was detected neither in stimulated nor in unstimulated cells. A PGE2 secretion could not be detected by ELISA. In contrast, we found no effect on cell growth, COX-2 and 15-PGDH expression of the MDA-MB-231 cells when treated by calcitriol (10 nM and 1 nM). Although PGE2 was synthesized 2.3-fold more by MDA-MB-231 cells than MCF-10F cells; the COX-2 expression was consistent with the MCF-10F cells, but 15-PDGH was expressed about 50 % less. As we have shown in MCF-7 cells, an expression of the VDR could not be detected.Conclusions: The growth inhibiting effect of calcitriol in MCF10F cells is associated with the increasing expression of VDR. and a remaining question is whether the loss of VDR goes along with the invasiveness of the breast cancer cell lines. Additionally, we suggest that the invasiveness of the breast cells is abetted by the increased COX-2 expression (MCF-7) or by the decreased expression of 15 PGDH (MDA-MB-231). These results suggest even more a link between vitamin D and prostaglandin metabolism and therefore a possible synergism between COX-2 inhibition and calcitriol in breast cancer cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5155.
ELUCIDATING THE ONCOGENIC ROLE OF ATRX DEFICIENCY IN GLIOMA
Authors: J. T. Huse
Journal: Neuro-Oncology (2014)

We and others recently identified loss-of-function mutations in the ATRX gene as core components of a highly recurrent molecular signature characterizing adult diffuse astrocytoma. ATRX deficiency has also been implicated in large subsets of pediatric glioma, neuroblastoma, and pancreatic neuroendocrine tumor. ATRX is a SWI/SNF chromatin remodeling factor, which appears to play a crucial role in heterochromatin maintenance, particularly at telomeres. Its dysfunction has been correlated with genomic instability and DNA replications stress, along with abnormal telomere elongation. Interestingly, germline mutations in ATRX do not cause cancer, but are instead associated with neurodegeneration and mental retardation. To further elucidate the pathogenic role of ATRX in glioma, we first assessed its expression level across different glioma subtypes. As expected, ATRX expression was lost in virtually all IDH-mutant gliomas without 1p/19q codeletion (primarily astrocytomas), but was universally maintained in IDH-wild type tumors (primarily glioblastomas), and 1p/19q co-deleted tumors (oligodendrogliomas). Interestingly, we found that ATRX-mutant gliomas were not universally negative for ATRX, with some tumor cells retaining expression. This finding, which we have confirmed by deep sequencing, suggests that ATRX mutations do not confer a strong proliferative advantage per se, but instead predispose cellular subclones to transformative events downstream, perhaps through genomic destabilization and DNA copy number alteration. To investigate issues of clonality and DNA copy number further, we have performed single cell sequencing on a number of ATRX-mutant gliomas, identifying several distinct subclones within each sample, and are in the process of integrating focused genotyping data for ATRX and other relevant genes. We are also in the process of a detailed investigation into the epigenomic and transformative consequences of ATRX deficiency using disease-relevant in vitro and in vivo modeling systems. Characterizing the pathogenic cascade induced by ATRX deficiency will provide crucial insights into therapeutic development for a number of tumor entities, including diffuse astrocytoma.
Feasibility, efficacy and safety of a pure natural orifice transluminal endoscopic gastrojejunostomy using a gastric outlet obstruction survival animal model
Authors: JM Gonzalez, EA Bonin, G Vanbiervliet, E Garnier, S Berdah, M Barthet
Journal: Endoscopy (2012)

Introduction: Natural orifice translumenal endoscopic surgery is a less invasive surgical technique for creating a gastrojejunal anastomosis without the need of skin/parietal incisions. Such procedure may be useful for bariatric procedures and for treating gastric outlet obstruction. A pure natural orifice transluminal endoscopic gastrojejunostomy remains experimental and technically challenging despite many efforts in developing the technique. The aim of this study is to determine feasibility, efficacy and safety of a pure endoscopic NOTES gastrojejunal anastomosis procedure (GJA) using a simulated gastric outlet obstruction (pyloric closure) survival swine model.
Crossover Inhibition Generates Sustained Visual Responses in the Inner Retina
Authors: Juliana M. Rosa, Sabine Ruehle, Huayu Ding, Leon Lagnado
Journal: Neuron (2016)

In daylight, the input to the retinal circuit is provided primarily by cone photoreceptors acting as band-pass filters, but the retinal output also contains neuronal populations transmitting sustained signals. Using in vivo imaging of genetically encoded calcium reporters, we investigated the circuits that generate these sustained channels within the inner retina of zebrafish. In OFF bipolar cells, sustained transmission was found to depend on crossover inhibition from the ON pathway through GABAergic amacrine cells. In ON bipolar cells, the amplitude of low-frequency signals was regulated by glycinergic amacrine cells, while GABAergic inhibition regulated the gain of band-pass signals. We also provide the first functional description of a subset of sustained ON bipolar cells in which synaptic activity was suppressed by fluctuations at frequencies above ∼0.2 Hz. These results map out the basic circuitry by which the inner retina generates sustained visual signals and describes a new function of crossover inhibition.
The effect of raloxifene on vascular endothelial growth factor expression in breast carcinomas of postmenopausal women.
Authors: BB da Silva, AR dos Santos, PV Lopes-Costa, CG Pires, G Facina, AC Nazário
Journal: Cancer Research (2009)

Abstract Abstract #1031 Background: To evaluate the effect of raloxifene on vascular endothelial growth factor (VEGF) expression in breast carcinomas of postmenopausal women. Materials and Methods: Sixteen postmenopausal patients with operable stage II, estrogen receptor-positive, infiltrating ductal breast carcinoma were treated with raloxifene at the dose of 60 mg/day for a period of 28 days prior to definitive surgery. Tumor size varied from 3 to 5 cm (mean 3.7 cm) and the mean age of patients was 61.8 years (range 49-72 years). Tumor samples were obtained by incisional biopsy at the time of diagnosis and again at the time of definitive surgical treatment. VEGF expression was obtained by immunohistochemistry (primary anti-VEGF monoclonal antibody, IgG, C-1, sc-7269, 200 mg/ml, Santa Cruz Biotechnology, Santa Cruz, USA). Evaluation of VEGF expression was assessed semiquantitatively based on the fraction of stained tumor cells and on the intensity of staining. McNemar's test of symmetry was used to evaluate agreement between the positive or negative classification of VEGF expression prior to and following raloxifene treatment (p&amp;lt;0.05). Results: Fourteen of the 16 patients (88%) were classified as positive for VEGF expression prior to raloxifene treatment, while only 5 (31%) were classified as positive following treatment (p&amp;lt;0.007) (see Figure 1 and Table 1).[figure1] &amp;#x2028; &amp;#x2028; Discussion: The results of the present study show that raloxifene reduced VEGF expression in breast cancer in postmenopausal women, thus suggesting that the drug may reduce neovascularization and the growth of estrogen receptor-positive breast tumors and reinforcing the argument for its possible use both in chemoprevention and in the treatment of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1031.
Molecular markers and stem-cell transplants: are they made for each other?
Authors: R J Schilder
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.5.1052 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7738610 Molecular markers and stem-cell transplants: are they made for each other? R J SchilderxR J SchilderSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.5.1052 First Page PDF © 1995 by American Society of Clinical Oncology
THU0078 Interactions of Antibodies Against Citrullinated Peptides with HLA Shared Epitope, PTPN22 1858T Variant, and Smoking in Individuals Prior to and after the Development of Rheumatoid Arthritis
Authors: H. Kokkonen, M. Brink, M. Hansson, L. Mathsson, E. Lassen, P. J. Jakobsson, R. Holmdahl, J. Rönnelid, L. Klareskog, S. Rantapää Dahlqvist
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Presence of antibodies against cyclic citrullinated peptides (ACPA) has been demonstrated to precede the development of rheumatoid arthritis (RA) by several years. The gene-environment interaction for these antibodies has not been clarified. <h3>Objectives</h3> To analyse for the development of reactivity against citrullinated peptides in the pre-disease phase of RA and after the onset of disease (i.e. diagnosis) in relation to genetic and environmental factors. <h3>Methods</h3> This study comprised 406 individuals, providing 717 samples who were identified before onset of symptoms of RA (median (IQR) 7.4 (9.3) years) as donors to the Medical Biobank of Northern Sweden. Among these, 204 were also sampled at the time of diagnosis. Analyses of antibodies against 10 different citrullinated peptides; Filaggrin, α-enolase (CEP1), collagen citC1 (CitC1<sup>III</sup>), Fibrinogen (Fib) α591, Fibα573, Fibβ72, Fibβ74, Fibβ36-52, Vimentin (Vim) 60-75, and Vim2-17 were performed using the ImmunoCAP ISAC®system (Phadia Diagnostics, Uppsala). Anti-CCP2 antibodies were analysed using ELISA (Euro-Diagnostica). HLA-SE alleles were genotyped using polymerase chain reaction sequence specific primers and genotyping of the <i>PTPN22</i> 1858C/T polymorphism was performed using a Taqman instrument. <h3>Results</h3> In individuals prior to onset of symptoms of RA, being positive for HLA-SE was associated with antibodies against Fibβ72, Fibβ74, and CCP2. HLA-SE positivity was associated with the development of antibodies against CCP2, Fibβ36-52, CEP-1, and Vim60-75 in individuals who prior to onset of symptoms were negative for the respective antibody but at the time of diagnosis turned positive. Smoking was associated with the development of positivity for Filaggrin, CEP-1, CitC1<sup>III</sup>, Fibα591, Fibα573, Fibβ36-52, and Vim60-75 antibodies. Interaction of smoking and HLA-SE after disease onset further increased the risk for development of antibodies against Filaggrin, Fibβ36-52, and CCP2. <h3>Conclusions</h3> Conversion to positivity for several of the antibodies after disease onset was associated with HLA-SE and/or smoking which was less evident during the pre-dating period. The different patterns in associations of the genetic markers and smoking with the various antibodies may reflect differences in the pathways leading to antibody development. <h3>Disclosure of Interest</h3> None Declared
P3-12-02: Intra-Operative Margin Assessment of Diffuse Disease with MarginProbe” as an Adjunct to Standard of Care, Results from a Randomized Prospective Multi Center Study.
Authors: SK Boolbol, C Cocilovo, L Tafra
Journal: Cancer Research (2011)

Abstract Background The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with diffuse disease such as DCIS and lobular pathology. A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decrease in the rate of patients requiring re-excision with these disease types. The current analysis stratified the data based on tumor type with a special focus on DCIS patients, patient with a DCIS component, and lobular patients. Methods: All 596 patients underwent breast conservation, with image-guided localization, and were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard lumpectomy procedure, including palpation followed by additional cavity resections as indicated. In the device arm, MarginProbe was used on each specimen margin and device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. Re-excision criteria were not dictated by the protocol. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were defined as those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy. Results: Results are presented in Table 1. The improvement in CSR was significant for all diagnosis types. The decrease in candidates for re-excision due to failed CSR was significant for all DCIS and mixed tumor types. Conclusions: Use of the device resulted in significant improvement in CSR and therefore a significant decrease in the need for reexcisions. Further studies should be conducted to evaluate the use of the device for additional patient cohorts, such as patients receiving neoadjuvant treatment and patients who have undergone prior breast surgery. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-02.
P12.08 * HIGH GRADE GLIOMAS IN ELOQUENT AREAS: SURGICAL RESULTS AFTER TAILORED CRANIOTOMY WITH INTRA-OPERATIVE NEUROPHYSIOLOGICAL MONITORING (IOM)
Authors: F. G. Legnani, R. Cordella, C. Casali, A. Saladino, L. Mattei, F. Prada, I. G. Vetrano, M. Del Bene, A. Filippini, F. DiMeco
Journal: Neuro-Oncology (2014)

BACKGROUND AND AIMS: Treatment of high grade gliomas is maximal safe resection followed by radiation and chemotherapy. When tumor is located in eloquent areas, the best practice would imply neurophysiological monitoring. To guarantee best mapping, some authors propose to perform routinely wide craniotomies to expose both the tumor and motor and language areas, whereas others prefer a smaller approach tailored on the lesion. In this study we present our data on motor performances in those patients harbouring a high grade glioma in motor areas operated on with a tailored craniotomy. METHODS: Data were collected for a series of 50 patients. An image-guided approach was performed including linear skin incision and craniotomy centred on the tumor. A 4-contacts-strip-electrode was positioned under the dura towards the motor strip to record electrocorticography, SSEP and motor evoked potentials. Brain mapping was performed stimulating the tumor and the surrounding cortex looking for negative and positive responses. Motor performances were evaluated with the BMRC 1-5 score. RESULTS: Adequate neurophysiological monitoring was achieved in all patients. Brain stimulation evoked muscular activity in 46% of patients: most cases had muscle response in hand or leg and fewer on the face muscles. Stimulation intensity ranged between 2 and 9mA. 21% of patients experienced worsening of their pre-existing deficits in the first week after surgery. At 3 month follow-up 50% of those patients had BMRC scores equal or better than before surgery. CONCLUSIONS: Our data suggest that fashioning a tailored craniotomy with IOM is safe and effective in preventing new motor deficits.
FDG PET Is a Robust Tool for the Diagnosis of Spondylodiscitis
Authors: Michael L. Prodromou, Panayiotis D. Ziakas, Loukia S. Poulou, Petros Karsaliakos, Loukas Thanos, Eleftherios Mylonakis
Journal: Clinical Nuclear Medicine (2014)

Spondylodiscitis is a rare infectious entity that requires multimodal diagnostic procedures. We evaluated the diagnostic performance of 18F-FDG PET on suspected spondylodiscitis based on published literature. We searched the PubMed and EMBASE for pertinent studies up to July 2013. We implemented a patient-based meta-analysis of diagnostic data for FDG PET (the index test) against clinical, laboratory, and/or radiologic evidence of disease (the reference standard). A bivariate analysis was implemented to account for variability beyond the threshold effect. The individual patient data analysis was used to assess confounding factors that moderate diagnostic performance. Twelve studies provided the diagnostic data on FDG PET and spondylodiscitis, comprising 224 patients. The combined sensitivity across studies was 0.97 [95% confidence interval (CI), 0.83-1.00], the specificity was 0.88 (95% CI, 0.74-0.95), and the area under the curve was 0.98 (95% CI, 0.96-0.99). For prior probabilities greater than 0.50, the corresponding positive predictive value was 0.96 (0.93-0.98), and the negative predictive value was 0.85 (0.82-0.88). In the individual patient data analysis, metallic implants, dual PET/CT scanners and the addition of other imaging modalities to confirm disease were significant outcome moderators; only PET/CT remained significant in the adjusted analysis. PET/CT scanners improved the diagnostic performance, as opposed to the clinical data (age, sex, lesion site), which did not alter outcome. FDG PET is a robust diagnostic test when spondylodiscitis is suspected and is excellent for exclusion of infectious spondylodiscitis given its low likelihood ratio negative (<0.1). Importantly, this diagnostic test is unaffected by other confounders, including the presence of implants, when PET/CT is used.