tbuckley/cabot-search huggingface dataset:
Abstract 4295: PHLPP suppresses epithelial-mesenchymal transition and cancer cell invasion by negatively regulating RAF1 activity.
Authors: Xin Li, Payton D. Stevens, Tianyan Gao
Journal: Cancer Research (2013)

Abstract PHLPP belongs to a family of protein phosphatases that have previously been shown to inhibit Akt-mediated cell proliferation and survival signaling in cancers. Here, we demonstrate that PHLPP exerts its tumor suppressor function by negatively regulating the RAF/MEK/ERK pathway to inhibit cell migration and invasion. Specifically, we identify the oncogenic protein kinase RAF1 as an interacting protein and a novel substrate of PHLPP. PHLPP dephosphorylates the S338 site of RAF1 and inactivates the kinase both in vitro and in cells. Loss of PHLPP expression largely increases the amplitude and duration of RAF/MEK/ERK signaling in cells, whereas overexpression of PHLPP inhibits the pathway. Functionally, knockdown of PHLPP induces epithelial-mesenchymal transition (EMT)-like phenotype, which coincides with a significant increase in migration and invasion in colon cancer cells. Furthermore, we show that upregulation of transcription factors ZEB1 and ZEB2 is responsible for increased invasiveness observed in PHLPP knockdown cells. Taken together, we have identified a novel role of PHLPP in suppressing EMT and cell motility in colon cancer cells by directly antagonizing RAF1 function. Citation Format: Xin Li, Payton D. Stevens, Tianyan Gao. PHLPP suppresses epithelial-mesenchymal transition and cancer cell invasion by negatively regulating RAF1 activity. [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 4295. doi:10.1158/1538-7445.AM2013-4295
AB1349 The effect of biological therapy on work participation in ankylosing spondylitis patients: A systematic review:
Authors: L. van der Burg, M. ter Wee, A. Boonen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the pre-biologics era several studies showed a large impact of ankylosing spondylitis (AS) on worker participation.[1] Biologicals offer the opportunity to improve work-outcomes on the one hand and offset part of the drug costs on the other hand. <h3>Objectives</h3> To systematically review the effect of treatment with biologicals in AS on three areas of work-outcomes: employment status, absence form paid work and at-work productivity loss. <h3>Methods</h3> A systematic search in Pubmed, Embase and Cochrane Library was performed (15 June 2011) by two authors to identify relevant articles. Quality of included studies was assessed by two authors using the Dutch Cochrane guidelines for (un)controlled cohorts and randomised controlled trials (RCTs). Data were extracted by one author (LvdB) and checked by another (MtW) using a self-composed form. Due to extensive inter-study heterogeneity, narrative summaries were used to present the data. <h3>Results</h3> A total of eight studies were included (5 uncontrolled cohorts, 1 population controlled cohort and 2 RCTs) and 26 comparisons of either before-after TNF or between treatment groups were reported. Overall 877 patients were treated with three different TNF-α inhibitors (etanercept, infliximab, adalimumab). While the methodological quality of RCTs was good, they lack external validity. Of the five cohort studies, three showed substantial selection bias and three did not control outcomes for potential confounders. Although trends for all outcomes were positive, only 7 of 13 before-after comparisons in the five uncontrolled cohorts were tested for statistical significance and 4 of 6 comparisons in the controlled cohort study (excluding the comparison with the general population). In the RCTs, only 4 out of 6 comparisons reported were tested for between group differences at the end of the trial. The table presents significance of results for number of comparisons made, organised by outcome. <h3>Conclusions</h3> Large heterogeneity in type and reporting of studies, and outcomes hampers clear conclusions. Although trends towards beneficial effects on all work outcomes were shown, this effect proved often not significant either compared to the untreated group or to the baseline situation. Since the majority of studies were (extensions of) controlled trials, the generalizability of the effect of biologicals on work participation in daily practice should be further studied in larger population controlled studies or registers. <h3>References</h3> Boonen A, van der Heijde D, Landewe R, et al. Work status and productivity costs due to ankylosing spondylitis: comparison of three European countries. Ann Rheum Dis. 2002 May;61(5):429-37. <h3>Disclosure of Interest</h3> None Declared
Dermoid Cyst Presenting as a “Cold” Thyroid Nodule
Authors: CODY A. COX, DAN L. NGUYEN, JESUS MEDINA, JOE C. LEONARD
Journal: Clinical Nuclear Medicine (1996)

The most common midline neck mass in a child is a thyroglossal duct cyst, and preoperative evaluation may involve thyroid scintigraphy to verify the presence and location of normal thyroid tissue.
DOBLE DERIVACIÓN ENDOSCÓPICA (DDE) PALIATIVA EN PACIENTES CON OBSTRUCCIÓN NEOPLÁSICA BILIAR Y DEL VACIAMIENTO GÁSTRICO: INTERVENCIONES Y RESULTADOS FUNCIONALES
Authors: G González, R Sánchez-Ocaña, A Loza, R Amo, V Busto, F Santos, H Núñez, P Díez, P Gil, C De La Serna, M Pérez-Miranda
Journal: Endoscopy (2014)

Introducción: Es posible la colocación endoscópica concomitante de stents biliares y duodenales (DDE) en pacientes con obstrucción biliar y al vaciamento gástrico simultáneas.
Prediction of Awakening after Out-of-Hospital Cardiac Arrest
Authors: W. T. Longstreth, Paula Diehr, Thomas S. Inui
Journal: New England Journal of Medicine (1983)

To develop a model that would forecast neurologic recovery after out-of-hospital cardiac arrest, we reviewed charts on 389 consecutive patients who were not awake on admission to the hospital after resuscitation from asystole or ventricular fibrillation. The outcome variable was "awakening," which was defined as having comprehensible speech or the ability to follow commands. Predictor variables that we considered included both preadmission and admission data. Using discriminant analysis, we derived models from a 60 per cent random sample of cases and tested the models on the remaining 40 per cent. We judged that the best model contained four variables from the admission examination: motor response, pupillary light response, spontaneous eye movements, and blood glucose (levels below 300 mg per deciliter predicted awakening). Overall correct classification was 80 per cent in the derivation sample and 77 per cent in the test sample. In a simplified form, the model's predictions of awakening had a sensitivity of 0.92, a specificity of 0.65, a positive predictive value of 0.80, and a negative predictive value of 0.84. This rule should be clinically useful in estimating the neurologic prognosis of patients resuscitated after out-of-hospital cardiac arrest. (N Engl J Med 1983; 308:1378–82.)
A5.12 SFRPS in cartilage biology: more than just WNT antagonists
Authors: Sarah Thysen, Frédéric Cailotto, Frank P. Luyten, Rik J. Lories
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives </h3> Wnts play an important role in cartilage development, homeostasis and degeneration. Therefore, exploring the therapeutic potential of factors that can modulate Wnts is of great interest. Secreted frizzled related proteins (SFRPs) were identified as secreted Wnt antagonists. Polymorphisms in Frizzled-related protein (<i>FRZB-SFRP3) are</i> associated with osteoarthritis (OA). Here, we study the role of SFRPs and their structural domains in cartilage biology. <h3>Materials and Methods<i></i></h3> <i>Surgical destabilization of the medial meniscus (DMM) was performed on eight-week-old male Frzb</i><sup>-/-</sup>, <i>Sfrp1<sup>-/-</sup></i>and wild-type mice. Eight weeks after surgery, mice were sacrificed and histological scores were determined for the femoral and tibial articular surfaces following the OARSI guidelines. Chondrogenesis of ATDC5 micromasses, stably overexpressing pcDNA3.1-FRZB, -FRZB-ΔCRD, -FRZB-ΔNTN, -SFRP1, -SFRP1-ΔCRD, -SFRP1-ΔNTN, pGIPZ-shmiRNA-Frzb or control plasmids, was induced by culturing cells for 14 days in DMEM/F12 + 5%FBS, supplemented with ITS (insulin, transferrin, sodium selenite). On day 14, cells were switched to mineralization medium (αMEM + 5%FBS, supplemented with ITS, β-glycerophosphate and ascorbic acid). mRNA expression of chondrogenic markers (Aggrecan, Col2a1 and Col10a1) were assessed by quantitative RT-PCR. Western blot was used to study canonical (β-catenin) and non-canonical (CamKII) Wnt signalling. <h3>Results </h3> The OARSI score showed a significant increase in cartilage damage in DMM-operated <i>Frzb</i><sup>-/-</sup>mice compared to wild-type but not in <i>Sfrp1<sup>-/-</sup></i>mice. Overexpression of <i>Frzb</i> in ATDC5 micromasses boosted chondrogenesis with up-regulation of <i>Col2a1</i>, whereas Frzb silencing lead to decreased chondrogenesis. These results corresponded with a reduction or increase in the activation of canonical WNT signalling, respectively. Wnt/CamKII signalling was not affected. SFRP1 overexpression led to a decrease in <i>Col2a1</i> transcription, but to an increase in Col10a1 expression. These results corresponded with increased activation of canonical WNT signalling pathway and decreased phosphorylation of CamKII. Domain studies for Frzb and Sfrp1 showed that overexpression of the NTN domain increased expression of <i>Col2a1</i> and <i>Aggrecan</i>. <h3>Conclusions</h3> Different SFRPs have a strong, but distinct effect on cartilage. Frzb promoted early chondrogenesis through modulation of canonical Wnt signalling. Sfrp1 reduced early chondrogenesis and favoured hypertrophy by affecting both canonical and non-canonical Wnt signalling. Domain studies revealed that the NTN domain of SFRPs is responsible for the positive effect on chondrogenesis.
Renal Transplantation in Black Americans
Authors: Carlton J. Young, Robert S. Gaston
Journal: New England Journal of Medicine (2000)

Despite remarkable social changes in the United States during the past century, issues related to race and ethnic background continue to permeate public discourse regarding health care.1,2 The influence of race on the delivery of care for end-stage renal disease remains especially controversial because of two seemingly unrelated factors. First, the incidence of kidney failure among black Americans is disproportionately high, resulting in the demographic anomaly of black overrepresentation in the population with end-stage renal disease. Second, passage of the Social Security Amendments of 1972 entitled virtually all people in the United States with end-stage renal disease to Medicare-funded . . .
Sensorimotor grounding and reused cognitive domains
Authors: Maria Brincker
Journal: Behavioral and Brain Sciences (2010)

Abstract Anderson suggests that theories of sensorimotor grounding are too narrow to account for his findings of widespread “reuse” supporting multiple different cognitive “task domains.” I call some of the methodological assumptions underlying this conclusion into question, and suggest that his examples reaffirm rather than undermine the special status of sensorimotor processes in cognitive evolution.
SAT0457 Efficacy and Safety of Etanercept in Combination with Methotrexate in the Patients with Early and Late Juvenile Idiopathic Arthritis
Authors: E. Alekseeva, T. Bzarova, A. Fetisova, S. Valieva, K. Isayeva, R. Denisova, T. Sleptsova, E. Mitenko, E. Chistyakova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The use of biological products in the therapy of juvenile idiopathic arthritis (JIA) enables to achieve sustained remission of the disease and to improve the prognosis. <h3>Objectives</h3> To assess efficacy and safety of Etanercept plus Methotrexate combination in the patients with early and late JIA. <h3>Methods</h3> 97 children with various JIA variants were examined. The patients were stratified into 2 groups: with late arthritis, the disease duration &gt; 2 years (Group 1, n=66), with early arthritis, the disease duration &lt; 2 years (Group 2, n=31). Average age of the children in Group 1 was 9.5 (3;17.0) years, in Group 2 – 5.0 years (1.0;14.0) years. The patients received subcutaneous Etanercept twice a week at the dose 0.4 mg/kg on top of Methottrexate at 15 mg/m<sup>2</sup>/week. The observation period was 52 weeks. Therapeutic efficacy was assessed in accordance with American College of Rheumatology criteria (ACR Pedi) as 50, 70, 90% improvement and remission criteria (Wallace, 2011). <h3>Results</h3> Based on ACR Pedi, one month after onset of Etanercept therapy 50% improvement was observed in 36% and 52% children in Groups 1 and 2, 70% improvement in 14% and 36% children, 90% improvement in 4% and 23% children, respectively. At 3 months 50%, 70%, 90% improvement was achieved in 51%, 44%, 50% of patients in Group 1 compared with 92%, 68% and 84% of patients in Group 2. At 6 months 50% improvement was recorded in 64% patients in Group 1 and in 96% patients in Group 2; 70% improvement – in 52% and 83% patients, respectively, 90% improvement was observed in 49% patients in Group 1 and у 78% patients in Group 2. Inactive disease stage was recorded in 71% patients in Group 1 and in 100% patients in Group 2. Twelve months after onset of treatment inactive disease stage was observed in 100% patients of the both groups; remission was observed in 71% patients in Group 1 and in 100% patients in group 2. In 11 patients Etanercept wsa discontinued for the following reasons: in 5 patients for inadequate efficacy; 1 patient for persistent local allergic reaction, in 3 patients for aggravation of JIA systemic manifestations; in 2 patients for development of rheumatoid uveitis. Adverse events were mild or moderate and included acute bronchitis, herpetic infection aggravation; acute rhinitis, and pain in administration site. <h3>Conclusions</h3> High efficacy and safety of Etanercept in the patients with early and late JIA was demonstrated. In the patients with early JIA the time to effect development is significantly shorter. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-237: Interaction between myopodin and integrin linked kinase (ILK) induces tumor suppression
Authors: Yanping Yu, Hui Wang, Jian-Hua Luo
Journal: Cancer Research (2010)

Abstract Myopodin, a tumor suppressor, is frequently deleted in invasive prostate cancers. Forced expression of myopodin in prostate cancer cells reduced tumor invasiveness and slowed cell motility. In our recent yeast two hybrid system analysis, we found that the N- terminal 326 amino acids of myopodin interacts with integrin linked kinase (ILK). This result was validated by co-immunoprecipitation of myopodin or ILK in cells expressing both proteins. In addition, the binding assays between ILK and myopodin were analyzed in vitro on a series of GST-myopodin deletion mutants with ILK. A binding motif of 78 amino acids in the N- terminus of myopodin was determined to be critical for ILK binding. Phosphorylation analyses through ILK knockdown or mutant assays in vivo and in vitro indicate that phosphorylation of myopodin is ILK dependent. Phosphorylation of myopodin by ILK leads suppression of cell motility and cell growth. Mutant myopodin that does not interact with ILK is not phosphorylated and is defective on suppressing cell motility and cell growth. These findings elucidate a novel signaling pathway of ILK-myopodin that leads to activation of a tumor suppressor. 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 LB-237.
ASCO Meeting Highlights Works in Progress
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article ASCO Meeting Highlights Works in Progress Get access Jean McCann Jean McCann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 12, 15 June 1994, Pages 892–894, https://doi.org/10.1093/jnci/86.12.892 Published: 15 June 1994
SAT0050 A novel function of junctional adhesion molecule-C in regulation of trans-endothelial migration of murine synovial fibroblasts
Authors: M. Heitzmann, A. Korb-Pap, C. Wunrau, G. Kollias, S. Butz, D. Vestweber, H. Pavenstädt, T. Pap
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent studies demonstrated the potential of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) to emigrate from affected joints and migrate via the bloodstream toward distant healthy cartilage in the SCID mouse model of disease. While the mechanisms of breaking endothelial barriers by RA-FLS are largely unclear, the junctional adhesion molecule C (JAM-C) has become of interest in this context due to its involvement in trans-endothelial migration of leukocytes. Using the human TNF transgenic (hTNFtg) mouse as a model for human RA, we studied the role of JAM-C in the transmigration of FLS derived from these mice. <h3>Methods</h3> The expression pattern of JAM-C on wild-type and hTNFtg FLS was analyzed by Western-blot and immunocytochemistry. We investigated the transmigratory capacity of these cells in a transmigration assay using murine endothelioma cells (bEnd.5) as an endothelial barrier, IL-1alpha treated murine cartilage tissue served as chemoattractant stimulus within this setting. Functional analyses included the knock down of JAM-C expression by siRNA against murine JAM-C as well as its neutralization by blocking antibodies. <h3>Results</h3> The expression of JAM-C could be detected on the surface of both wild-type and hTNFtg FLS and it was primarly located on sites of cell-cell interactions. Additionally, Western blot data showed an elevated expression of JAM-C in FLS from hTNFtg mice. Our transmigration experiments demonstrated a markedly higher potential of hTNFtg FLS to migrate through the endothelial monolayer than FLS from wild-type mice (+40%, p≤0.05), and cartilage explants pre-treated with IL-1alpha as chemoattractant strengthened the migratory capacity of hTNFtg FLS. Interestingly, knock down of JAM-C expression on hTNFtg FLS mediated by siRNA decreased the number of transmigrated cells of about 40% comparing with mock control (p≤0.01). Equally, the neutralization of JAM-C by blocking antibodies against murine JAM-C resulted in a reduction of transmigration on a similar level. <h3>Conclusions</h3> The inflammatory environment characteristic for joints of hTNFtg mice induces an up-regulation of JAM-C on FLS similar to that of human FLS during RA. Moreover, the differentiation of a trans-migrating phenotype of FLS, capable to break through endothelial barriers is supported by this environment. In this context, JAM-C seems to be contributed to this process of transmigration and, thus, to the extravasation of FLS and, therefore targeting JAM-C may be a promising therapeutic strategy for RA. <h3>Disclosure of Interest</h3> None Declared
Abstract P5-06-02: The Role of Breast Tumor Kinase (Brk) in Cell Cycle Control
Authors: AS Nimnual, E Chan
Journal: Cancer Research (2012)

Abstract Brk promotes cell proliferation and has been associated with multiple mitogenic pathways. However, the role of Brk in the cell cycle is still elusive. Here, we present a mechanism of Brk-induced cell cycle progression. Brk downregulates the cell cycle inhibitor p27 by altering its transcription factor FoxO3a subcellular localization. p27 is a key component of the G1/S cell cycle checkpoint and downregulation of p27 promotes S phase entry. The progression of the cell from G1 to S phase, induced by Brk, is independent of growth factors suggesting a role for Brk in malignant transformation. FoxO3a appears to be a major component in p27 down-regulation by Brk as the effect of Brk on p27 expression is significantly abrogated in cells transfected with siRNA targeting FoxO3a. The induction of FoxO3a nuclear exclusion by Brk is inhibited by LY294002 indicating that the mechanism is mediated by the PI3-kinase/Akt pathway. The mechanism underlying PI3-kinase mediated Brk function is still under investigation with evidence suggesting the involvement of the translocation of epidermal growth factor receptor. These data suggest that perturbation of p27 expression induced by Brk causes S phase entrance. Deregulation of the cell cycle is a key event in neoplasia, and thus, the mechanism presented here likely contributes to breast cancer development. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-06-02.
808 MODELING HCV KINETICS DURING INTRAVENOUS SILIBININ MONOTHERAPY IN THE PERI-TRANSPLANT PERIOD
Authors: S. DebRoy, Z. Mariño, G. Crespo, M. Navasa, M. D'Amato, S.J. Cotler, X. Forns, H. Dahari
Journal: Journal of Hepatology (2013)
Environmental Pollution: An Under-recognized Threat to Children’s Health, Especially in Low- and Middle-Income Countries
Authors: William A. Suk, Hamid Ahanchian, Kwadwo Ansong Asante, David O. Carpenter, Fernando Diaz-Barriga, Eun-Hee Ha, Xia Huo, Malcolm King, Mathuros Ruchirawat, Emerson R. da Silva, Leith Sly, Peter D. Sly, Renato T. Stein, Martin van den Berg, Heather Zar, Philip J. Landrigan
Journal: Environmental Health Perspectives (2016)

SummaryExposures to environmental pollutants during windows of developmental vulnerability in early life can cause disease and death in infancy and childhood as well as chronic, non-communicable diseases that may manifest at any point across the life span. Patterns of pollution and pollution-related disease change as countries move through economic development. Environmental pollution is now recognized as a major cause of morbidity and mortality in low- and middle-income countries (LMICs). According to the World Health Organization, pollution is responsible for 8.9 million deaths around the world each year; of these, 94% (8.4 million) are in LMICs. Toxic chemical pollution is growing into a major threat to children’s health in LMICs. The disease and disability caused by environmental pollution have great economic costs, and these costs can undercut trajectories of national development. To combat pollution, improved programs of public health and environmental protection are needed in countries at every level of development. Pollution control strategies and technologies that have been developed in high-income countries must now be transferred to LMICs to assist these emerging economies to avoid the mistakes of the past. A new international clearinghouse is needed to define and track the health effects of pollution, quantify the economic costs of these effects, and direct much needed attention to environmental pollution as a risk factor for disease.