tbuckley/cabot-search huggingface dataset:
Abstract 663: YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion
Authors: Said Rahim, Elspeth M. Beauchamp, Yali Kong, Milton L. Brown, Jeffrey A. Toretsky, Aykut Üren
Journal: Cancer Research (2011)

Abstract Chromosomal translocations involving the ETS family of transcription factors are found in a majority of prostate cancers, including the most clinically aggressive forms. These translocations produce a chimeric gene, which fuses the promoter region of an androgen responsive gene, such as TMPRSS2, to the coding region of ETS factors, most frequently ETV1 or ERG. Over-expression of ETS factors in prostate cancer cells results in a more invasive phenotype. The high prevalence of these rearrangements, and their biological significance represents a novel therapeutic target for the treatment of prostate cancer. We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing's Sarcoma. ERG and ETV1 belong to the same class of ETS factors as FLI1. Due to the close homology of FLI1 with ERG and ETV1, we tested the ability of YK-4-279 to inhibit ETS biological activity in prostate cell-lines such as VCaP and LNCaP that demonstrate androgen dependent ERG and ETV1 expression, respectively. YK-4-279 inhibited ERG and ETV1 mediated transcription of target genes such as PLAU, PLAT, ADAM19 and MMP-13, which are involved in breakdown of the extracellular matrix and metastasis. YK-4-279 reduced the motility and invasive phenotype of ETV1-fusion positive LNCaP cells and ERG fusion-positive VCaP cells in in vitro invasion assays. However, ETS fusion-negative PC-3 cells were unresponsive to YK-4-279. ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Transient ERG expression in PC-3 cells resulted in an increased invasive phenotype, which was reduced by YK-4-279. Our results demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells leading to decreased motility and invasion. Therefore, YK-4-279 may have an impact on metastasis in prostate cancer, which is a leading cause of death, and it may be further evaluated for its clinical applications in prostate cancer, in addition to Ewing's sarcoma. 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 663. doi:10.1158/1538-7445.AM2011-663
FRI0336 Medium doses of glucocorticoids are as effective as and safer than high doses of glucocorticoids in patients with giant cell arteritis
Authors: I. Les, A. Martínez Berriotxoa, R. Rodríguez, M. V. Egurbide, G. Ruiz-Irastorza
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> After the advent of methotrexate, there are not comparative studies between different regimes of prednisone in giant cell arteritis (GCA). Due the complications of an excessive prednisone cumulative dose<sup>1</sup>, a prednisone maintenance dose≤7.5 mg/day is recommended<sup>2</sup>. <h3>Objectives</h3> To compare the efficacy and safety of a medium (≤30 mg/day, group A) and a high (&gt;30 mg/day, group B) prednisone starting dose and to identify factors related to remission taking a safe maintenance dose. <h3>Methods</h3> Retrospective study including all patients with GCA of our unit between 2004 and 2012. Standard treatment was methylprednisolone pulses followed by prednisone as monotherapy or combined with methotrexate based on clinical criteria. The primary end-point was time to clinical and biological remission together with a prednisone maintenance dose≤7.5 mg/day. A Cox regression was performed to assess factors related to the primary end-point. <h3>Results</h3> 103 patients (A:53, B:50) were followed for 3.3±2.1 years. Both groups exhibited similar baseline features including methotrexate combination except for visual symptoms (A:11, B:24 patients). Patients in group A had a shorter time to primary end-point (log-rank test, p=0.01) without resulting in an increase in relapses (A:21, B:25 patients, p=0.29) or disease-related complications (A:6, B:9 patients, p=0.33). There was a difference in the prednisone cumulative dose at 6 months (A:2.4±0.7, B:3.8±1.8 grams, p&lt;0.01) that was related to a higher number of adverse effects (A:24, B:33 patients, p=0.03). Factors related to the primary end-point were lymphoplasmacytic infiltrate in the temporal artery biopsy (HR=0.55, p=0.01), induction with methylprednisolone pulses (HR=1.97, p=0.01) and occurrence of adverse effects (HR=0.48, p&lt;0.01). <h3>Image/graph</h3> <h3>Conclusions</h3> In patients with GCA, a medium (≤30 mg/day) prednisone starting dose is at least as effective as and safer than a high (&gt;30 mg/day) starting dose. Inflammatory signs in temporal artery, lack of methylprednisolone pulses and development of adverse effects may be related to a worse therapeutic response. <h3>References</h3> Nesher G, et al. Efficacy and adverse effects of different corticosteroid dose regimens in temporal arteritis: a retrospective study. <i>Clin Exp Rheumatol</i> 1997;15:303-6. Hoes JN, et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. <i>Ann Rheum Dis</i> 2007;66:1560-7. <b>Disclosure of Interest</b>: None Declared
SP0153 How to obtain consent from children and their families
Authors: N. Ruperto
Journal: Annals of the Rheumatic Diseases (2013)

Implementation of clinical trial, observational studies or in general research projects that aim to collect data collection of the health status of patients requires the primary need to obtain a proper approval of the research study from the ethics committee/institutional review board according to European Union (EU) guidelines and nationals laws. In addition participation of the patients elicit the need to obtain a proper consent from the patient. In case of participation of minors the consent must be obtained from the parents with the addition of an assent for children with an appropriate developmental age to understand its content. Until few years ago most of the drugs administered in pediatrics were used off-label but this situation changed recently in Europe with the adoption of a pediatric legislation that facilitate the implementation of clinical trials for new drugs. In addition the EU has adopted directives in order to provide guideline for review by ethics committee and for consent/assent procedures. There is however still a substantial burden to implement clinical studies in children. For example a recent study conducted by the Paediatric Rheumatology International Trials Organisation (PRINTO at www.printo.it) in a rare disease such as juvenile dermatomyositis (JDM) with off label drugs used in current clinical practice worldwide has required activation of 103 clinical centers to enroll 130 patients and the ethical process required by review boards took two years. Of note 97% of the ethical review boards gave their approval without requesting any change at all. Procedures should be implemented at a European level to facilitate implementation and conduct of studies in children by simplifying the bureaucratic burden that is now placed on research in children. <h3>Disclosure of Interest</h3> None Declared
A memorable patient: The accordionist
Authors: P. Vincent
Journal: BMJ (1999)

“Cedric” was a house call in Kibblesworth. I knew him slightly from a couple of previous visits to his equally ancient wife, now sadly passed on. I didn’t want to go to Kibblesworth. It’s a small village stranded on the other side of the practice, and in the opposite direction to a cosy cup of lunchtime tea at home. Cedric’s little bungalow was clearly missing the attention it used to have from his wife. He had had some sort of episode on the way to the post office where “he wasn’t himself,” not sure of where he was, etc, but he seemed to have more or less recovered.

While musing on the diagnostic possibilities I saw a music stand and a small bass guitar amp in the corner. My curiosity was aroused; it was hard to visualise 86 year old Cedric as a rocker (other than in a parkinsonian way), so I asked about his music. His eyes lit up, and from under a cloth he produced a magnificent black and silver accordion. He invited me to play it, which I did, badly. Despite his arthritic fingers he played it himself, a tune that he had written, a lovely lyrical tune. Then he showed me a trunk full of accordion music. 

“That’s worth a pretty penny,” he said proudly, pointing to dog eared music costing three and sixpence a sheet.Then he turned to his photographs of his army band playing days after the war. His eyes misted up and he wasn’t really with me. But I wasn’t in the bungalow either. I, too, was in smoky postwar dance halls listening to the band. 

“We were the best band around,” he said. He should have turned professional, but he went down the pit instead. Perhaps that was what had made him so hardy. He continued to reminisce.

“Ah, but once they just started vamping on the bass, the accordion’s days were numbered,” he finished up sadly, as he carefully replaced the cloth. There was nothing more to say. I left for a late lunch.

And the diagnosis? I never did make one, but at least now I had visited a person, not a patient, and it made my day.
SAT0195 Impact of mycophenolate mofetil and/or corticosteroid treatment on outcomes of belimumab treatment in SLE:
Authors: M. Schneider, J. Buyon, M.A. Dooley, E.M. Ginzler, S. Cooper, Z.J. Zhong, G.F. Keenan, J.T. Merrill
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Corticosteroids, antimalarials, and immunossuppressants, including mycophenolate mofetil (MMF), were permitted as background standard therapy in patients participating in the belimumab BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) SLE phase 3 trials. Belimumab is a B-lymphocyte stimulator-specific inhibitor approved for treatment of SLE combined with standard therapy. <h3>Objectives</h3> To compare SLE responder index (SRI) rates in patients treated with MMF or corticosteroids in the placebo (standard therapy alone) vs belimumab dosing groups. <h3>Methods</h3> Post-hoc analysis examined manifestations of SLE in patients treated with MMF or corticosteroids in the placebo vs belimumab arms by reviewing baseline (BL) SELENA-SLEDAI and BILAG organ domain scores. Response rates at 52 wk were assessed by SRI. <h3>Results</h3> 189 patients entered the trials on MMF. Patients whose BL manifestations included renal (proteinuria with MMF 26.5% vs no MMF 11.6%) or vasculitic (MMF 9.5% vs no MMF 6.2%) activity were more likely to be receiving treatment with MMF or corticosteroids. Corticosteroid use was also more frequent in patients with positive immunologic findings: low complement, corticosteroids 68.3% vs no corticosteroids 60.6%; and anti-double-stranded DNA, corticosteroids 75.7% vs no corticosteroids 68.2%. SRI rates are shown in table. <h3>Conclusions</h3> The subset of patients treated with MMF ± corticosteroids at entry in the BLISS trials does not appear to be random. Trends of increased renal disease and vasculitis, low complement, and anti-double-stranded DNA suggest these patients represent a more active SLE population. In post-hoc analysis, addition of belimumab in patients receiving these background therapies suggests the possibility of greater benefit than in the overall population. <h3>Disclosure of Interest</h3> M. Schneider Consultant for: GlaxoSmithKline/Human Genome Sciences, Speakers Bureau: GlaxoSmithKline/Human Genome Sciences, J. Buyon Grant/Research support from: Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences, M. Dooley Grant/Research support from: GlaxoSmithKline/Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences, E. Ginzler Grant/Research support from: GlaxoSmithKline/Human Genome Sciences, Consultant for: GlaxoSmithKline/Human Genome Sciences, S. Cooper Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, Z. Zhong Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, G. Keenan Shareholder of: Human Genome Sciences, Employee of: Human Genome Sciences, J. Merrill Consultant for: GlaxoSmithKline/Human Genome Sciences
Comparison of EUS-FNA with 25gage, 22gage, and 19gage needle
Authors: Maya Watanabe
Journal: Endoscopy (2011)

Background: After Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for Gastroenterological diseases was firstly reported in 1992, EUS-FNA has become popular in the clinical fields. It has been reported that the usefulness for diagnosing and treatment of gastrointestinal and bilio-pancreatic diseases. There are lots of instruments for EUS-FNA that have been developed in order to improve the accuracy of diagnosis. At the moment needle sizes of EUS-FNA commonly used are 19G, 22G and 25G. As increasing the size of needle, the larger tissue might be obtained, however it becomes rather difficult to puncture the targets for EUS-FNA. There are several report about 19G, true cut needle and 22G needle, and as conclusion, there is not significant difference between 19G and 22G. On the other hand, 25G needle has started to be employed frequently. Because diagnostic adequacy of 25G needle for pulmonary diseases showed in 92% and with a definitive diagnosis in 88% of cases. And a smaller needle size decreases potential of complications such as bleeding etc. However 22G needle is commonly employed in the clinical fields.
P168Anti-hypercholesterolemic effect of a preparation of vitamins, minerals and trace elements in experimental hyperlipidemia
Authors: M Sarkozy, G Szucs, CS Szucs, J Barkanyi, P Bencsik, R Gaspar, CS Csonka, CS Konya, P Ferdinandy, T Csont
Journal: Cardiovascular Research (2014)

Although multivitamin products are widely used as dietary supplements, the effects of these products were not investigated in hypercholesterolemia which is a major risk factor of cardiovascular diseases. Therefore, here we investigated if a preparation of different minerals, vitamins, phytosterols and trace elements (MVT) developed for human use affects the severity of experimental hyperlipidemia as well as myocardial ischemia/reperfusion injury. Male Wistar rats were fed a normal or a 2% cholesterol plus 0.2% cholic acid-enriched diet for 12 weeks to induce hyperlipidemia. From week 8, rats in both groups were fed with an MVT preparation or placebo for 4 weeks. Serum triglyceride and cholesterol levels were measured at week 0, 8 and 12. At week 12, hearts were isolated, perfused according to Langendorff and subjected to a 30-min coronary occlusion followed by 120 min reperfusion. At week 8, cholesterol plus cholic acid-fed rats showed significantly higher serum cholesterol level as compared to normal rats, however, serum triglyceride level did not change. At week 12, MVT treatment significanty decreased serum cholesterol level in the hyperlipidemic group, however, MVT treatment failed to decrease infarct size in the hyperlipidemic hearts. In the normolipidemic group, MVT treatment did not influence the serum cholesterol level or the infarct size. We conclude that MVT treatment reduces serum cholesterol level in hyperlipidemia, however, it fails to decrease infarct size.
Abstract 3096: c-Myc regulates MAP4K1 expression and AP-1 activity in Pdcd4 knock-down cells
Authors: Hsin-Sheng Yang, Qing Wang
Journal: Cancer Research (2010)

Abstract Programmed Cell Death 4 (Pdcd4) is a novel tumor suppressor that frequently exhibits down-regulated expression in several types of cancer. In colon cancer tissues, expression level of Pdcd4 is continuously down-regulated in the order of normal-adenoma-carcinoma. Over-expression of Pdcd4 has been demonstrated to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation and tumor phenotype. In addition to cultured cells, Pdcd4 transgenic mice that over-express Pdcd4 in the epidermis show significant reductions in 7,12-dimethylbenz(a)anthracene (DMBA)/TPA induced skin papilloma formation and carcinoma incidence. Knock-out of Pdcd4 expression in mice resulted in induction of lymphomas with frequent metastases to the liver and kidneys, and an increase in DMBA/TPA induced skin papilloma formation and carcinoma incidence. These findings suggest that Pdcd4 suppresses carcinogenesis not only at an early stage (tumor promotion), but also at a late stage (tumor progression) in both cultured cells and transgenic mice. Recently, we demonstrated that over-expression of Pdcd4 inhibits invasion and MAP4K1 expression in colon tumor cells. Conversely, knock-down of Pdcd4 promotes invasion, activates AP-1 and β-catenin/Tcf dependent transcription, and up-regulates c-Myc expression in colon tumor cells. However, how MAP4K1 expression is regulated by Pdcd4 remains unknown. MAP4K1, a kinase upstream of JNK signaling pathway, is also known as HPK1 (haematopoietic progenitor kinase 1) whose function and expression regulation in solid tumors is not well studied. It has been known that activation of MAP4K1 results in activation of JNK, c-Jun and AP-1 dependent transcription. In the present study, we found that MAP4K1 expression is up-regulated by Pdcd4 knock-down. Concurrently, the phosphorylation of JNK and c-Jun is increased in Pdcd4 knock-down cells. c-Myc is a direct downstream target gene of β-catenin/Tcf dependent transcription and is up-regulated by Pdcd4 knock-down. To investigate the role of c-Myc in regulating MAP4K1 expression, we over-expressed c-Myc in HEK293 cells and found that over-expression of c-Myc induces MAP4K1 expression and activates c-Jun. Using chromatin immunoprecipitation, we demonstrate that c-Myc directly binds to MAP4K1 promoter in Pdcd4 knock-down cells. Down-regulation of c-Myc using c-myc RNAi reverses MAP4K1 expression and c-Jun activation in Pdcd4 knock-down cells. Thus, these results provide an insight into how Pdcd4 regulates MAP4K1 expression and AP-1 dependent transcription. 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 3096.
Abstract 2231: The over-activation of Akt1 oncogene heightens the Glypican-3 (GPC3) effects on metastatic progression of murine mammary tumor cells
Authors: Silvina A. Romero, Maria A. Lago Huvelle, Guillermo D. Peluffo, Elisa Bal de Kier Joffe, Alejandro J. Urtreger, Maria G. Peters
Journal: Cancer Research (2012)

Abstract It is known that Akt kinases 1, 2 and 3 have critical roles in regulating survival, metabolism and other cellular activities. However, their functions on migratory potential and metastasis development are less clear. GPC3 is a proteoglycan downregulated in breast tumors. We have previously shown that GPC3 reexpression inhibits metastatic capacity in vivo of the LM3 murine mammary adenocarcinoma cells. Moreover, this phenomenon was associated with a partial reversion of the epithelial-to-mesenchymal transition as shown in vitro. On the other hand, we have also determined that GPC3 modulates Akt signaling pathway in LM3 cells. The aim of this work was to investigate the role of Akt1 on the invasive/metastatic behavior of GPC3 reexpressing cells. First, we have confirmed that LM3-GPC3 cells present higher Akt1 levels than LM3-vector ones by western blot. To elucidate the function of this isoform, LM3-GPC3 clones were infected with viruses carrying a constitutively active variant of Akt1 (CA Akt1). Although there were no changes in the actin cytoskeleton organization, we could determine by a wound healing assay that LM3-GPC3-CA Akt1 cells were less migrant than their controls (Wound coverage: LM3-GPC3 control=50% vs. LM3-GPC3-CA Akt1=30%, p&amp;lt;0.05). To address an in vivo effect, different clones were injected s.c. into syngeneic female BALB/c mice. We found that these tumors did not differ in their growth rate, reaching a similar size at 30 days post inoculation (LM3-vector= 189±25, LM3-GPC3= 181±40, LM3-GPC3-CA Akt1= 200±51 mm3). No differences were found in either tumor incidence or in tumor latency. In order to study the experimental metastatic ability, all cell lines were i.v. inoculated. We observed that LM3-GPC3-CA Akt1 tumors developed fewer lung metastases than controls (Median [Range]: LM3-GPC3 control=9 [3-29] vs. LM3-GPC3 CA Akt1=0.5 [0-10], p&amp;lt;0.05). Moreover, the LM3-GPC3-CA Akt1 metastatic nodes were also of a smaller size (&amp;lt;0.5 mm). In sum, our results suggest that Akt1 expression and signaling could be mediating GPC3 inhibitory effect on the metastatic dissemination. The over-activation of this oncogene would exacerbate or heighten GPC3 effects, preventing the metastasis progression through the reduction of cell migration. 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 2231. doi:1538-7445.AM2012-2231
Cellular-Telephone Use and Brain Tumors
Authors: Peter D. Inskip, Robert E. Tarone, Elizabeth E. Hatch, Timothy C. Wilcosky, William R. Shapiro, Robert G. Selker, Howard A. Fine, Peter M. Black, Jay S. Loeffler, Martha S. Linet
Journal: New England Journal of Medicine (2001)

Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices.
Abstract 2427: The stress response controls the interorgan glutathione/interleukin-6 cycling activity: A systemic signaling mechanism promoting metastases growth.
Authors: Jose M. Estrela, Elena Obrador, Salvador Mena, Maria L. Rodriguez, Jose A. Pellicer, Miguel Asensi, Soraya L. Vallés, Maria Benlloch
Journal: Cancer Research (2012)

Abstract B16 melanoma F10 (B16-F10) cells with high glutathione (GSH) content show very high metastatic activity in vivo. An intertissue flow of GSH, where the liver is the main reservoir, increases GSH content in metastatic cells and promote their growth. We studied possible tumor-derived molecular signals that could activate GSH release from hepatocytes. GSH efflux increases in hepatocytes isolated from mice bearing liver or lung metastases, thus suggesting a systemic mechanism. Fractionation of serum-free conditioned medium from cultured B16-F10 cells and monoclonal antibody-induced neutralization techniques facilitated identification of interleukin (IL)-6 as a tumor-derived molecule promoting GSH efflux in hepatocytes. IL-6 activates GSH release through a methionine-sensitive/organic anion transporter polypeptide 1- and multidrug resistance protein 1-independent channel located on the sinusoidal site of hepatocytes. Specific siRNAs were used to knock down key factors in the main signaling pathways activated by IL-6, which revealed a STAT3-dependent mechanism. Our results show that IL-6 (mainly of tumor origin) facilitates GSH release from hepatocytes and its interorgan transport to metastatic growing foci. Metastatic tumor activated the hypothalamic-pituitary-adrenal axis, thus increasing expression of hypothalamic corticotropin releasing factor and plasma levels of adrenocorticotropin hormone, corticosterone, and cathecolamines. Corticosterone and norepinephrine increased IL-6 expression and synthesis in metastatic cells, thus promoting the interorgan GSH/IL-6 cycling activity. Our results suggest possible mechanisms of cross-talk between metastases and the central nervous system of the host. 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 2427. doi:1538-7445.AM2012-2427