tbuckley/cabot-search huggingface dataset:
Abstract 2046: FoxM1 cooperates with Sp1 to transcriptionally activate the COX-2 promoter
Authors: Kaiming Xu, Hui-Kuo G. Shu
Journal: Cancer Research (2011)

Abstract Cyclooxygenase-2 (COX-2) induction by epidermal growth factor (EGF) is likely to be an important response to this growth factor in gliomas given its prognostic significance in these tumors. Gaining a greater understanding of the signaling pathway(s) involved in this response may permit development of novel approaches for disrupting this induction with potential therapeutic benefit in such patients. Previously, we showed that p38-MAPK and protein kinase C-delta were required signal transducers in this process that ultimately leads to Sp1-dependent transcriptional activation of the COX-2 promoter in glioma cells. In this current work, we find that the FoxM1 transcription factor is also needed for full induction of COX-2 in response to EGF. Src kinase acts upstream of p38-MAPK to induce both FoxM1 and COX-2 expression. Furthermore, siRNA suppression of FoxM1 significantly reduces COX-2 induction in response to both EGF and the downstream signal transducers Src and p38-MAPK. In addition, increased expression of FoxM1 in an inducible system leads to increased COX-2 expression. Evaluation of the COX-2 promoter in a reporter gene system revealed that while FoxM1 overexpression can have a small effect on promoter activity through the FoxM1 consensus site at approximately -2.5k upstream of the promoter start site, its main activity appears to be through the Sp1 consensus site located from -245 to -240 upstream of the start site. Interestingly, FoxM1 associates with Sp1 by coimmunoprecipitation. In fact, FoxM1 can associate with the Sp1 consensus site both in vitro as assessed by electrophoretic mobility shift assay (EMSA) and in vivo as assessed by a chromatin immunoprecipitation (CHIP) assay. This work demonstrates a novel interaction between Sp1 and FoxM1 whereby FoxM1 can activate transcription of COX-2 through the associated Sp1 factor's consensus site. 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 2046. doi:10.1158/1538-7445.AM2011-2046
AB0542 Blocking the Human B Lymphocyte Stimulator Molecule (BLYS) Using A Monoclonal Antibody (Belimumab) in Systemic Lupus Erythematosus: First Results in Real-Life Spanish Patients with Refractory Disease (Biogeas-Semi Registry)
Authors: P. Brito Zeron, L. Caminal-Montero, A. Chamorro, J. de la Hera Fernández, A. Gato, A. Marín-Ballvé, A. Robles, M. Rodríguez-Carballeira, G. Salvador, L. Saez, G. Ruiz-Irastorza, H. Gheitasi, S. Retamozo, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To analyze the efficacy and safety of treatment with belimumab, a monoclonal antibody that specifically binds the soluble form of the protein human B lymphocyte stimulator B (BLyS), in SLE patients refractory to standard treatment. <h3>Methods</h3> In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS registry, a multicenter study recruiting patients with refractory systemic autoimmune diseases treated with biological agents. <h3>Results</h3> On December 31, 2013, a total of 10 patients treated with belimumab were included in the BIOGEAS Registry, 9 females and 1 male, with a mean age of 41.8 years (range 24-71 years). These patients were heavily treated, with a mean of 7 years of corticosteroid treatment, antimalarials and at least one immunosuppressive agent, mycophenolate in 9, azathioprine in 7, metothrexate in 4, cyclosphosphamide in 2, cyclosporine A in 2, tacrolimus in 2 and talidomide in 2. Belimumab (10mg/kg) was administered in combination with corticosteroids (in all patients), antimalarials (6 patients) and immunosuppressive agents (8 patients, 6 with mycophenolate). The baseline average activity score (SELENA-SLEDAI) was 12 (range 6-33); 8 patients had high titers of anti-dsDNA and/or hypocomplementemia. Therapeutic indication included refractory mucocutaneous involvement (4 patients), refractory vasculitis (3 patients), systemic disease (2 patients) and refractory lupus nephritis (1 patient). After a mean follow-up of 7 months (range 2-12), clinical response could be evaluated in 9 patients, 8 classified as responders (improvement greater than 80% in 5 patients), while the remaining patient was classified as stable. Two patients (20%) developed adverse events (raised transaminases and systemic cryptococcosis due to severe CD4 lymphopenia); there were no deaths or lupus flares. <h3>Conclusions</h3> These postmarketing data in Spanish SLE patients in whom belimumab was used following the recommendations approved by the FDA/EMA (refractory disease to standard treatment, clinical and immunological active disease, SELENA-SLEDAI&gt;6) have showed promising results, with a good therapeutic response and a safety profile similar to other biological therapies used off-label in patients with SLE. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5447
SAT0237 Dublin Uveitis Evaluation Tool (DUET): A Proposed Algorithm and Its Performance Evaluation for the Best Referral By Ophthalmologists of Acute Anterior Uveitis Patients with Possible Underlying Spondyloarthropathy
Authors: M. Haroon, P. Ramasamy, M. O’Rourke, C. Murphy, O. FitzGerald
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent reports claim that the prevalence figures of mostly undiagnosed underlying Spondyloarthropathy (SpA) is more than 60% among patients presenting with acute anterior uveitis (AAU). To date, there are no formal guidelines or referral pathways for AAU patients developed or endorsed by any international or national societies. Therefore, in a condition where significant delay in diagnosis is common, and where AAU may frequently be the first interaction with medical care, an opportunity to identify SpA early is often missed leading to less than ideal care. <h3>Objectives</h3> The objectives of our study were: (1) to develop an assessment algorithm for referral from Ophthalmologists of appropriate AAU patients to Rheumatology that will aid the early diagnosis of the SpA; (2) to explore whether modifications of this novel algorithm might further improve sensitivity and specificity; and (3) to investigate the prevalence of undiagnosed SpA in patients presenting with AAU in a primary care ophthalmology setting. <h3>Methods</h3> All consecutive patients attending emergency department of local ophthalmology hospital with AAU, but who did not have a known diagnosis of SpA, were eligible to partake in this study. Patients with any other known cause of AAU were excluded. The HLA-B27 status was checked in all patients, and assessment and onward referral was made as per a test algorithm which combined clinical features and HLA-B27. Patients without risk factors for SpA and who were HLA-B27 negative remained part of the study as a control group; these patients also underwent detailed rheumatologic evaluation. <h3>Results</h3> 104 consecutive patients who attended the ophthalmology emergency department from September 2011 through to June 2012 were recruited. Mean age of the cohort was 42±15 years. and HLA- B27 was positive in 52.5%. According to the test algorithm, 71 out of 104 patients were referred to rheumatologists; 69 of them had complete rheumatologic assessment. After rheumatologic evaluation, 41.6% (n=42) of these patients were diagnosed with SpA as per ASAS classification criteria. Of these newly diagnosed patients, 64.3% had radiographic axial SpA. Non radiographic SpA patients were noted to have shorter duration of backache (p=0.03). Our test algorithm was noted to have: sensitivity 100%, specificity 53.5%, PPV 61% and NPV 100%. Further regression analysis revealed that algorithm version-1 could make the following improvements: sensitivity 95%, specificity 98%, PPV 97.5%, NPV 96.6%. <h3>Image/graph</h3> <h3>Conclusions</h3> 41.5% of patients presenting with idiopathic AAU have undiagnosed SpA. A simple to apply algorithm is described with excellent sensitivity and specificity that is currently being validated in an additional cohort. <h3>Disclosure of Interest</h3> None Declared
LONG-TERM SURVIVAL AND FOLLOW-UP IN PATIENTS WITH CONNECTIVE TISSUE DISORDERS UNDERGOING EXTENSIVE OPEN REPAIRS OF THORACOABDOMINAL AORTIC ANEURYSMS
Authors: Gabriele Di Luozzo, Erin Lewis, Sarah Geisbuesch, Themba Nyirenda, Aaron Weiss, Amit Pawale, Randall Griepp, David Spielvogel
Journal: Journal of the American College of Cardiology (2015)
Group-level traits emerge
Authors: Paul E. Smaldino
Journal: Behavioral and Brain Sciences (2014)

Abstract Most commentators supported the thesis of the target article, though there were also those who were less fully persuaded. I will begin with a response to the most critical commentaries. First, I will justify an evolutionary perspective that includes group organization and nongenetic inheritance. Next, I will discuss the concept of emergence. Following that, I will transition to an exploration of ideas and concerns brought up by some of the more supportive commentators. This will include a discussion of different types of groups; the psychology of group-level traits; the uses and limitations of an institutional perspective; the link between transmission, adaptation, and selection; current and future methodologies; and the variety of fields that may benefit from a group-level traits perspective.
Intensive Postremission Chemotherapy in Adults with Acute Myeloid Leukemia
Authors: Robert J. Mayer, Roger B. Davis, Charles A. Schiffer, Deborah T. Berg, Bayard L. Powell, Philip Schulman, George A. Omura, Joseph O. Moore, O. Ross McIntyre, Emil Frei
Journal: New England Journal of Medicine (1994)

About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions.We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment.Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups.These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.
Smoking-Attributable Cancer Mortality
Authors: EDWARD J. SONDIK
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Smoking-Attributable Cancer Mortality Get access EDWARD J. SONDIK EDWARD J. SONDIK Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 24, 18 December 1991, Page 1834, https://doi.org/10.1093/jnci/83.24.1834 Published: 18 December 1991
Abstract SY31-03: Genome regulation by long noncoding RNAs.
Authors: Howard Y. Chang
Journal: Cancer Research (2013)

Abstract The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serves as the template for protein synthesis. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. An emerging theme from multiple model systems is that LncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. I will discuss how this mode of regulation is particularly relevant to cancer and the maintenance of genome integrity. Citation Format: Howard Y. Chang. Genome regulation by long noncoding RNAs. [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 SY31-03. doi:10.1158/1538-7445.AM2013-SY31-03
What inspired me?
Authors: Chang-Qing Gao
Journal: Journal of the Royal Society of Medicine (2012)

I was born in China in the middle of the 1960s in a once-rich family. Unlike today, at that time in our country the rich bore the stigma of exploitation. The exploiters and their families were sent from the cities to the countryside for re-education. Our family was among those unlucky people.

Intensive labor made my mother sick. Lying in bed, she asked the barefoot doctor: ‘It seems that one of my backbones is protruding like the beads on the abacus now, is that normal?’ He sat five meters away from my mother, and without even looking at the affected site, answered: ‘It should be all right’. After taking months of his and his colleague's prescriptions without any improvement, my mother said: ‘They are doctors, aren't they?’ I knew that she felt helpless and that she was just talking to herself, for I was too young to answer her question. Since then, her question has always been echoing in my mind.

From the late 1970s onward, the fate of the Chinese had changed. So did that of my family. In the summer of 1980 I went to medical school, where I learnt in pathology that the abnormality in my mother's back was one of the typical signs of spinal tuberculosis. The lesion in the textbook depicting such a patient looked so similar to that of my mother. I wondered whether the barefoot doctors could identify the signs of that disease, even if they had examined her.

After graduation from medical school, I was appointed to work at a big hospital in Beijing. One day I felt quite happy, because my diagnosis was confirmed by pathological examination while my peers were still puzzling. I went to the patient and told him that he should begin chemotherapy.

‘How long can I live with treatment?’ He asked.

‘Usually, 2 to 3 years.’ I answered.

‘Only three years?’ He seemed not to believe what he heard. Staring at me, he appeared quite surprised. His eyes then moved away from my face and looked at the floor in desperation.

My contented mood immediately vanished and I felt deeply guilty. ‘Am I a Doctor?’ I asked myself.

Lying in bed at night, I pondered: ‘Can I do more for patients like him?’

Hiding in the laboratory, I began an attempt to find a solution for all the unanswered questions. This is what I am still doing.
AB0060 The association of HLA-B*51 expression with endoplasmic reticulum stress
Authors: F. Cosan, Z. Emrence, H. Azakli, S. Sirma, E. Aktas-Cetin, N. Abaci, D. Ustek
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Endoplasmic reticulum is an organel, where the proteins are folded. Misfolding of the proteins causes the endoplasmic reticulum stress. Unfolded protein response occurs for compansating of ER stress. It was shown the UPR molecules play role in the pathogenesis of several diseases. It was suggested, that HLA-B*27, the major genetic susceptibility for AS, is associated with UPR. HLA-B*51, which has the same Bw4 region and associated with BD, may have similar misfolding pattern. <h3>Objectives</h3> We aimed to investigate the association between the expression of HLA-B*51 and UPR molecules. <h3>Methods</h3> HLA-B*5 expressing monocyte cell line Thp-1 monocytes and from Thp-1 derived macrophages cell cultures were stimulated with LPS, ATP, IFN, Tunicamycin. After 8 and 24 h stimulation, mRNAs were isolated and the expression of ATF6, IRE1, PERK, XBP-1, BIP were performed with quantitative PCR. In addition PBMCs from HLA-B*51 (+), (-) and B*27(+), (-) 8 individuals were cultured, with the same agents stimulated and quantitative PCR was performed. The correlation analysis was performed with using SPSS 16.0. <h3>Results</h3> We found that HLA-expression is correlated with IRE1 (r(12)=.957, p&lt;0,01), PERK (r(12)=.974, p&lt;0,01), ATF6 (r(12)=.952, p&lt;0,01), BIP (r (12)=.610, p&lt;0,05) in Thp-1 monocytes. A strong correlation also found with BIP (r(12)=.808, p&lt;0,01) and ATF6 (r(12)=.626, p&lt;0,05) expression in Thp-1 derived macrophages. In HLA-B51(+) PBMC cell culture the correlation was found with PERK (r(12)=.535, p&lt;0,05) and ATF6 (r(12)=.622, p&lt;0,05) expression. There was no similarity in the expression of UPR molecules in HLA-B*51 (-) cell cultures. In HLA-B*51 expressing PBMC derived macrophages, a correlation was detected between HLA and IRE1 (r(12)=.746, p&lt;0,01), PERK (r(12)=.696, p&lt;0,01) and ATF6 (r(12)=.558, p&lt;0,05). Increased HLA expression was also found correlated with PERK (r(12)=.903, p&lt;0,01) and ATF6 (r(12)=.706, p&lt;0,01) in HLA-B*27(+) PBMC culture. In HLA-B*51 and B*27 (-) cell cultures it was no similar and strong UPR response to different stimulant agents. <h3>Conclusions</h3> Our data reveals that it is a strong association between the expression of HLA-B*51 and spesific UPR molecules after stimulation, while the HLA-B*51 and B*27 negative cultures did not respond to stimulant agents in similar pattern. In the monocytes HLA-B*51 expression is found especially correlated with PERK and ATF6. This finding may show the role of ER stress in BD pathogenesis. <h3>Disclosure of Interest</h3> None Declared
Disclosing Cancer Diagnosis to a Patient
Authors: R. BLOCH
Journal: JNCI Journal of the National Cancer Institute (1994)

and the results were in agreement; 2) the interval between end of exposure and time of blood collection for the subject with a serum level of 34 ppt was about 24 years.Using a serum TCDD half-life of 7.1 years, this interval is just over three half-lives long.A simple arithmetic calculation, even without use of our formula, would indicate that the estimated level at the time exposure ceased for this individual is roughly around the 329 ppt predicted with the formula.
A3.24 Alterations in χδ T Cells Homeostasis in Systemic Sclerosis
Authors: Tiago Carvalheiro, Mariana Santiago, Cláudia Silva, Maria João Salvador, José António P Silva, Artur Paiva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic Sclerosis (SSc) is an autoimmune disease characterised by inflammation and extracellular matrix deposition. There are growing evidences of immune cells alterations, mainly in T cells subsets, including γδ T cells. <h3>Objectives</h3> Evaluate the frequency of γδ T cells, their distribution among naïve, memory and effector functional compartments, the cytotoxic activity and γδ repertoire in SSc patients. <h3>Materials and Methods</h3> The study enrolled 43 SSc patients, 30 of limited subtype (lSSc) and 13 of diffuse subtype (dSSc). Additionally 14% of the patients had less than 1 year since diagnosis, 49% ranging between 1 and 10 years and 37% with more than 10 years since diagnosis. The healthy control group (HG) included 20 age and gender matched individuals. The phenotypic and functional activity of γδ T cells was assessed by flow cytometry. <h3>Results</h3> It was observed a lower frequency of γδ T cells in SSc patients compared to HG. Regarding the cytotoxic activity, it was verified a higher frequency of γδ T cells expressing granzime B and perforin in SSc group, particularly in lSSc, with a higher γδ T cells cytotoxic activity in patients with more than 10 years since the disease onset. Moreover, an increased frequency of γδ T cells with a naïve and effector phenotypes was observed in SSc group and these alterations were more evident in dSSc patients. Additionally, patients with pulmonary fibrosis demonstrated an increased frequency of effector memory and naïve γδ T cells closely associated to the decrease of central memory cells, when compared to patients without this clinical feature. Patients with more than 10 years since the disease onset, compared to those with less than 1 year since disease diagnosis, presented a higher frequency of effector cells associated to the decrease of central memory cells. Concerning γδ TCR repertoire assigned by Vδ2 and Vγ9 chains, it was observed in patients with SSc for more than 10 years, an increase of Vδ2<sup>–</sup>Vγ9<sup>–</sup> repertoire in naïve, central memory and effector γδ T cells when compared to patients with less than 1 year since diagnosis, which exhibit predominantly a Vδ2<sup>+</sup>Vγ9<sup>+</sup> and Vδ2<sup>+</sup>Vγ9<sup>–</sup> repertoire. <h3>Conclusions</h3> Important alterations were observed in the frequency, cytotoxic activity, distribution among functional compartments and in γδ T cell receptor repertoire in peripheral blood γδ T cells that seem to be related to the time of disease after diagnosis or to clinical findings.