tbuckley/cabot-search huggingface dataset:
Abstract 5286: Beta-arrestin2-CARMA3 signaling axis is required in lysophosphatidic acid-induced ovarian cancer migration and invasion
Authors: Jiyuan Sun, Jingli Cai, Yumei Feng, Lei Guo
Journal: Cancer Research (2010)

Abstract Ovarian cancer is ranked as the 4th most common type of cancer among women in the United States. One of the biomarkers of ovarian cancer is lysophosphatidic acid (LPA). LPA is a type of G protein-coupled receptor ligand. It is strikingly elevated in 90% of ovarian cancer patients. Additionally, LPA receptors are aberrantly up-regulated in ovarian cancer patients. We have reported previously that a signaling axis consisting of beta-arrestin 2 and CARMA3 (CARD and MAGUK domain-containing protein 3) is indispensable in LPA-induced nuclear factor kappa B (NF-kappaB) activation in mouse embryonic fibroblast cells. NF-kappaB is an important transcription factor, which has been suggested to mediate LPA-induced ovarian cancer migration and invasion. However, it remains unknown whether the beta-arrestin2-CARMA3 signaling axis plays an important role in LPA-induced ovarian cancer cell migration and invasion. In the present study, using beta-arrestin 2 and CARMA3 shRNA, we knockdowned their protein expression levels in ovarian cancer cell lines. Consistent with previous reports, we found that down-regulation of beta-arrestin 2 and CARMA3 abolished LPA-induced IKK activity and NF-kappaB activation in ovarian cancer cells. In addition, in vitro transwell migration and matrigel invasion assays demonstrated that beta-arrestin 2 and CARMA3 shRNA significantly impaired LPA-induced ovarian cancer cell motility and invasiveness. Together, our results provide the evidence that beta-arrestin 2 and CARMA3 serve as critical regulators in LPA-induced, NF-kappaB-mediated ovarian cancer migration and invasion. Therefore, we speculate that beta-arrestin 2 and CARMA3 may represent attractive therapeutic targets for ovarian cancer and many other types of malignancies. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5286.
P-182 Clinical outcomes of a phase II study of nelfinavir, a hypoxia-modifying agent, in combination with chemoradiotherapy in locally-advanced pancreatic cancer – functional imaging is prognostic and provides proof of mechanism
Authors: J. Wilson, S. Hackett, L. Durrant, S. Dutton, K.-Y. Chu, C. Eccles, A. Abraham, E. O'Neill, M. Partridge, M. Hawkins, W. McKenna, T. Maughan, T. Brunner, S. Mukherjee
Journal: Annals of Oncology (2015)
Inorganic particles in human tissues and their association with neoplastic disease
Authors: Arthur M. Langer
Journal: Environmental Health Perspectives (1974)

An increased gastrointestinal cancer risk is associated with occupational exposure to asbestos fiber. Examination of tissues obtained from extrapulmonary organs of exposed workmen demonstrates the presence of asbestos fibers and bodies. The amount of fiber present in these tissues is many magnitudes less than encountered in the lung tissues from the same individuals. Ingestion of asbestos fiber in some environmental instances may approach in magnitude the amount resulting from occupational exposure. Disease factors are discussed.
AB0254 Clinical utility of natural angiogenin antibodies in pediatric osteosarcoma patients
Authors: Y. Savitskaya, G. Rico, L. Linares, E. Delgado, E. Estrada, E. Martinez, R. Tellez, C. Ibarra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Children are most commonly diagnosed with osteosarcoma at 14 years. Early osteosarcoma detection is key to ensuring effective treatment. Tumour angiogenesis is one of the most important hallmarks of osteosarcoma, which enables its development, progression and metastasizing. The study of natural antibodies to tumor antigens has come to the attention of many researchers. Circulating markers found in the sera offer a minimally invasive method that can be used repeatedly over the course of treatment. <h3>Objectives</h3> The aim of the study was to investigate if natural angiogenin antibodies (ANG-IgM) can be clinically useful for pediatric osteosarcoma patients. <h3>Methods</h3> The study consisted of 87 patients (median age 14 years) with osteosarcoma and 87 healthy age matched counterparts. Serum ANG-IgM was analyzed by a novel ELISA in patients at time of diagnosis, during treatment and after therapy. Computed tomography angiography was performed in all the osteosarcoma patients. <h3>Results</h3> We observed that before treatment serum ANG-IgM level in pediatric osteosarcoma patients was significantly higher (P&lt;0.05) compared to that obtained in healthy children. During chemotherapy the value of ANG-IgM significantly decreased by 20-30%. After therapy we observed different serum level of ANG-IgM in patients with favorable and unfavorable prognosis. Serum ANG-IgM level was higher in patients with progression as compared to patients with remission of disease (P&lt;0.01). Patients with poor prognosis had also higher serum level of ANG-IgM in comparison to patients with remission (P&lt;0.01). <h3>Conclusions</h3> Presented results suggest that ANG-IgM identify changes in tumour angiogenesis in pediatric osteosarcoma patients during anticancer therapy. These markers due to the non-invasive methods and their specificity might be useful in monitoring of clinical treatment of osteosarcoma patients. <h3>References</h3> Poon RT: Clinical Implications of Circulating Angiogenic Factors in Cancer Patients. J Clin Oncol 2001, 19(4):1207-1225. Vollmers HP: Natural IgM Antibodies, the Ignored Weapons in Tumour Immunity. Histol Histopathol 2004, 19(3):897-905. <h3>Disclosure of Interest</h3> Y. Savitskaya Grant/Research support from: FONSEC SSA/IMSS/ISSSTE/CONACyT SALUD-2010-C01, G. Rico: None Declared, L. Linares: None Declared, E. Delgado: None Declared, E. Estrada: None Declared, E. Martinez: None Declared, R. Tellez: None Declared, C. Ibarra: None Declared
OP0270 Osteoporotic Hip Fractures in Extreme Elderly Men: A Growing Problem
Authors: A. Sehgal, A. Mithal, A. Mannalithara, G. Singh, G. Triadafilopoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Extreme elderly (EE or &gt;80 years) men are the fastest growing segment of population due to rapid declining cardiovascular mortality and better medical care. There is little epidemiologic data on osteoporotic hip fractures in EE men compared to women even though EE will form more than 25% of US population by 2050. <h3>Objectives</h3> To study trends in osteoporotic hip fracture hospitalizations in the EE men and women from 1993 to 2008. <h3>Methods</h3> We examined all EE hospitalizations in Nationwide Inpatient Sample (NIS) from 1993 to 2008 with a diagnosis of non-traumatic (osteoporotic) hip fractures. The NIS is a stratified random sample of all US community hospitals and includes data on over 37.5 million hospitalizations per year. <h3>Results</h3> We studied 2.88 million osteoporotic hip fracture hospitalizations in 150.98 million person-years (PY) of observation in EE individuals from 1993 to 2008. Of these, 2.26 million hip fractures occurred in 99.8 million EE women-years of observation and 626,000 occurred in 51 million EE men-years of observation. Hip fracture hospitalizations in EE women decreased from 136,956 in 1993 (2,618 per 1,000 PY) to 136,494 in 2008 (1,874 per 1,000 PY), even as the population of EE women increased by 39% from 5.2 million in 1993 to 7.2 million in 2008 perhaps reflecting increasing awareness, screening and treatment for osteoporosis in elderly women. However, in EE men, hip fracture hospitalizations increased from 35,252 in 1993 to 43,934 in 2008, even as the prevalence (per 1000 PY) decreased from 1,427 in 1993 to 1,100 in 2008. This increase in hip fracture hospitalizations, in spite of decreasing prevalence is coincident with the dramatic rise in the number of the EE men, from 2.47 million in 1993 to 3.99 million in 2008 (61.6% increase). <h3>Image/graph</h3> <h3>Conclusions</h3> Osteoporotic hip fractures pose a growing problem in the EE, more so than older adults, increasing their risk for hospitalization, morbidity and mortality greatly. Despite an overall decrease in prevalence, the absolute number of osteoporotic hip fractures continues to increase in EE men since significantly more men are living past their 80<sup>th</sup> year of life. Aggressive measures towards recognition, prevention and therapy of osteoporosis during the medical care of EE, both ambulatory and in assisted living facilities is needed. <h3>Disclosure of Interest</h3> None Declared
Evolution of the<i>APETALA2</i>Gene Lineage in Seed Plants
Authors: Cecilia Zumajo-Cardona, Natalia Pabón-Mora
Journal: Molecular Biology and Evolution (2016)

Gene duplication is a fundamental source of functional evolutionary change and has been associated with organismal diversification and the acquisition of novel features. The APETALA2/ETHYLENE RESPONSIVE ELEMENT-BINDING FACTOR (AP2/ERF) genes are exclusive to vascular plants and have been classified into the AP2-like and ERF-like clades. The AP2-like clade includes the AINTEGUMENTA (ANT) and the euAPETALA2 (euAP2) genes, both regulated by miR172. Arabidopsis has two paralogs in the euAP2 clade, namely APETALA2 (AP2) and TARGET OF EAT3 (TOE3) that control flowering time, meristem determinacy, sepal and petal identity and fruit development. euAP2 genes are likely functionally divergent outside Brassicaceae, as they control fruit development in tomato, and regulate inflorescence meristematic activity in maize. We studied the evolution and expression patterns of euAP2/TOE3 genes to assess large scale and local duplications and evaluate protein motifs likely related with functional changes across seed plants. We sampled euAP2/TOE3 genes from vascular plants and have found three major duplications and a few taxon-specific duplications. Here, we report conserved and new motifs across euAP2/TOE3 proteins and conclude that proteins predating the Brassicaceae duplication are more similar to AP2 than TOE3. Expression data show a shift from restricted expression in leaves, carpels, and fruits in non-core eudicots and asterids to a broader expression of euAP2 genes in leaves, all floral organs and fruits in rosids. Altogether, our data show a functional trend where the canonical A-function (sepal and petal identity) is exclusive to Brassicaceae and it is likely not maintained outside of rosids.
Benign Hepatic Cyst Mimicking a Functional Thyroid Carcinoma Metastasis on Whole-Body I-131 Imaging
Authors: DISHAN H. GUNAWARDANA, ALEX G. PITMAN, MEIR LICHTENSTEIN
Journal: Clinical Nuclear Medicine (2003)

From the *Department of Nuclear Medicine, Royal Melbourne Hospital, Victoria, Australia Received for publication August 28, 2002. Revision accepted November 21, 2002. Reprint requests: Dishan Gunawardana, Department of Nuclear Medicine, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. E-mail: [email protected]
847 COFFEE INTERFERES WITH HCV REPLICATION IN VITRO BY INHIBITION OF WNT SIGNALING
Authors: A.D. Keller, K. Singethan, A. Wuestenberg, V. Lohmann, R. Bartenschlager, M. Dandri, U. Protzer, G. Tiegs, G. Sass
Journal: Journal of Hepatology (2012)
Abstract 211: Control of integrin expression and signaling by claudin-3 and claudin-4 in ovarian cancer.
Authors: Xinjian Lin, Xiying Shang, Gerald Manorek, Stephen Howell
Journal: Cancer Research (2013)

Abstract Changes in cell-cell and cell-matrix adhesion are central to ovarian cancer metastasis. We have previously demonstrated that the two major tight junction proteins claudin-3 (CLDN3) and claudin-4 (CLDN4) function to restrain in vivo growth and metastatic potential of ovarian cancer cells by sustaining expression of E-cadherin and limiting β-catenin signaling. Here we report that CLDN3 and CLDN4 control integrin αvβ3 expression and signaling through which they regulate cell-matrix adhesion and anchorage-dependent growth. Knockdown of CLDN3 or CLDN4 in human ovarian carcinoma cells reduced their ability to adhere to fibronectin whereas increased expression of CLDN3 or CLDN4 enhanced adherence to the extracellular matrix protein. A flow cytometric analysis revealed that CLDN3 and CLDN4 knockdown reduced αvβ3 complex formation at the cell surface by a factor of 1.7- and 12.4-fold, respectively, relative to the parental 2008 cells. Deconvoluting microscopic analysis of immunocytochemically stained cells confirmed the reduction in αvβ3 expression in the CLDN3KD and CLDN4KD cells. Measurement of β3 mRNA levels by qRT-PCR demonstrated a 55 ± 11.0% reduction in the CLDN3KD cells and a 51 ± 13.7% decrease in the CLDN4KD cells while the αv mRNA level was not affected. Interestingly, ablation of αvβ3 increased CLDN3 and CLDN4 expression at both the mRNA and protein level. Anchorage-independent growth was markedly reduced in both CLDN3KD and CLDN4KD cells with respect to the number and the size distribution of the colonies that formed in soft agar. Moreover, loss of either CLDN3 or CLDN4 resulted in activation of focal adhesion kinase (FAK) as the phosphorylation of Tyr-397 residue within FAK, which reflects FAK activity, was significantly increased in the CLDN3 and CLDN4 knockdown cells. Taken together, these results indicate a novel role for CLDN3 and CLDN4 in regulating integrin αvβ3 expression and signaling that control cell-matrix adhesion and aggressiveness of the ovarian carcinoma cells. Citation Format: Xinjian Lin, Xiying Shang, Gerald Manorek, Stephen Howell. Control of integrin expression and signaling by claudin-3 and claudin-4 in ovarian cancer. [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 211. doi:10.1158/1538-7445.AM2013-211 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
PTU-069 740 Patient Years Of Anti-tnf Safety Data In Crohn’s Disease Patients: Abstract PTU-069 Table 1
Authors: B Miller, R Kalla, M Daghem, S Campbell
Journal: Gut (2014)

<h3>Introduction</h3> Anti-Tumour Necrosis Factor alpha antibodies (anti-TNFs) are widely used for the treatment of severe and fistulising Crohn’s Disease (CD). They are, however, associated with a number of adverse events (AEs) including infections, neutropenia, malignancy, demyelinating disease and infusion reactions. We aimed to evaluate the safety profiles Adalimumab (Al) and Infliximab (Ifx) amongst patients with CD at Central Manchester University Hospitals. <h3>Methods</h3> 217 CD pts were identified retrospectively from our anti-TNF database; data was retrieved from clinic letters. A probit regression was used to correlate AEs and pt characteristics. <h3>Results</h3> Median age of pts was 41 (range 20–79) yrs. Total lifetime yrs on anti-TNFs was 740.6 (331.2 on Ifx, 409.4 on Al) yrs. 133 pts were treated with Ifx (75 females), 4 had previously been on Al. Median length of Rx with Ifx was 20 (range 1 dose-still on at 140) months. 98 (73.6%) pts on Ifx were on a concomitant immunomodulator drug. 141 pts were treated with Al (79 females), 53 had previously been on Ifx. Median length of Rx with Al was 33 (range &lt;1-still on at 89) months. 62 (44.0%) pts on Al were on a concomitant immunomodulator. 54 (40.6%) pts had AEs whilst on Ifx (see Table 1 for severity), including lymphoma (2 pts), solid organ tumours (3), pulmonary TB (2), infusion reaction (13), cutaneous side effects (SEs) (7), other infections (12). 33 pts were still on Ifx at the time of this study. 30 pts (22.6%) stopped Ifx due to AEs. 13 pts had an infusion reaction. Pts were most likely to have an infusion reaction at infusion 2 (6 pts). Overall, 57 (39.7%) pts suffered from AEs on Al (see Table 1 for severity), including solid organ tumours (2 pts), cutaneous SEs (10), neurological symptoms (3) and other viral/bacterial infections (28). 88 pts were still on Al at the time of this study. 21 pts (14.9%) stopped Al due to AEs. Pts were more likely to suffer from an AE with increasing age (p = 0.041 for Ifx, p = 0.016 for Al). Patients over 50 yrs were more likely to suffer from an AE than those less than 50 (p = 0.015 for Ifx, p = 0.015 for Al). Pts over 70 yrs were more likely to suffer from a moderate or severe AE on Al (p = 0.009), there was no relationship for Ifx. Gender, smoking status and use of immunomodulators had no effect on AEs. No significant relationship found between length of Rx and development of AEs. No statistically significant difference found in AEs frequency between Ifx and Al. <h3>Conclusion</h3> This study found that AEs are independent of the length of time on anti-TNFs, but are associated with increasing age of the patient. Patients over 50 yrs are more likely to have an AE on Ifx and Al. Patients over 70 yrs are more likely to have a moderate or severe AE on Al. <h3>Disclosure of Interest</h3> None Declared.
A META-ANALYSIS OF MULTI-VESSEL VERSUS CULPRIT ARTERY ONLY PERCUTANEOUS CORONARY INTERVENTION IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Alexandre Benjo, Daniel Garcia, Christopher White, Rhanderson Cardoso, Francisco Macedo, Alan Schob, Georges El-Hayek, Girish Nadkarni, Emad Aziz, Rajan Patel
Journal: Journal of the American College of Cardiology (2015)
Src-Mediated EGF Receptor Activation Regulates Ozone-Induced Interleukin 8 Expression in Human Bronchial Epithelial Cells
Authors: Weidong Wu, Phillip A. Wages, Robert B. Devlin, David Diaz-Sanchez, David B. Peden, James M. Samet
Journal: Environmental Health Perspectives (2014)

Human exposure to ozone (O3) results in pulmonary function decrements and airway inflammation. The mechanisms underlying these adverse effects remain unclear. Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of lung inflammation.We examined the role of EGFR activation in O3-induced expression of the chemokine interleukin 8 (IL-8) in human bronchial epithelial cells (HBEC).We detected phosphorylated EGFR using immunoblotting. EGFR dimerization was examined through cross-linking reaction and immunoblotting, and levels of IL-8 protein were measured using ELISA.Exposure to O3 (0.25-1.0 ppm) induced rapid and marked increase in EGFR phosphorylation at the autophosphorylation site Y1068 and the transphosphorylation site Y845, implicating the involvement of Src kinase. Further investigation showed that O3 stimulation induced phosphorylation of Src at Y416, indicative of Src activation. Pharmacological inhibition of Src kinase activity abrogated O3-induced EGFR phosphorylation at tyrosines 1068 and 845. Moreover, pretreatment of BEAS-2B cells with inhibitor of either EGFR or Src kinase activities significantly blocked O3-induced IL-8 expression.O3 exposure increased IL-8 expression through Src-mediated EGFR transactivation in HBEC.
Different Metastatic Pattern According to the EGFR Mutational Status in a Cohort of Lung Adenocarcinomas (ADCS): a Single-Institution Report
Authors: A. Russo, T. Franchina, A. Picone, G. Ferraro, M. Picciotto, M. Zanghì, V. Franchina, V. Adamo
Journal: Annals of Oncology (2015)
New abortion guidance in Northern Ireland places greater emphasis on women’s health
Authors: Clare Dyer
Journal: BMJ (2016)

New official abortion guidelines have been issued for health professionals in Northern Ireland, where the law has been one of the strictest in Europe.1

The new guidance offers a more liberal interpretation of the law than earlier draft guidelines, which never came into force but had a chilling effect on doctors. The number of NHS abortions in Northern Ireland, already low at 51 in 2012-13, fell to only 16 in 2014-15.2

Doctors have been calling for years for clear guidance on when abortions are covered by the Northern Ireland law, which permits terminations only when the pregnancy threatens the life of the mother or serious, long lasting damage to her mental or physical health.3

England, Wales, and Scotland are covered by the Abortion Act 1967, which …
Practical Preventive Therapy for Tuberculosis?
Authors: Christopher Dye
Journal: New England Journal of Medicine (2011)

Every new episode of tuberculosis — there were 9 million in 20101 — follows a period of asymptomatic infection lasting from weeks to decades. These subclinical infections, which are detectable with a tuberculin skin test or interferon-γ release assay, offer a target for prophylactic treatment either with drugs or, potentially, a vaccine. Vaccination after infection is not yet an option, but drug treatment has been available for 60 years in the form of 6 to 12 months of isoniazid preventive therapy (IPT), which protects up to 90% of infected persons from active tuberculosis. And yet very few tuberculosis-control programs have . . .
Abstract 4186: miR-218 suppresses invasion and migration via inhibition of ZEB2 and N-Cadherin in colon cancer.
Authors: Jasmin Batliner, Mohammed Abba, Christine Hauser, Heike Allgayer
Journal: Cancer Research (2013)

Abstract The great majority of cancer deaths are due to metastasis. A hallmark of cancer metastasis is the process of epithelial to mesenchymal transition (EMT), in which cells alter their gene expression program resulting in loss of their epithelial characteristics and gain of typical mesenchymal properties. Recently, microRNAs have been shown to play key roles in the dynamic process of EMT, orchestrating a coordinated multi-target repression of genes and, together with master transcription factors, act in regulatory networks to alter cell function. We used a miRNA-microarray platform to identify differentially expressed microRNA genes in primary tumor, distant metastatic and corresponding normal samples in a cohort of resected patient tissues. From our list of differentially regulated microRNAs we focused on miR-218 as so far very little information has been accumulated regarding its function in cancer. In our microarray analysis, miR-218 was significantly downregulated in tumor/metastatic tissue compared to normal colon tissue. We validated miR-218 expression in an additional series of 42 colorectal cancer patient tissues, where we found a significant downregulation of miR-218 in tumor as compared to the corresponding normal tissues in over 80% of cases. Furthermore, ectopic expression of miR-218 significantly reduced in vitro invasion and migration of invasive colorectal cancer cell lines and upregulated the key epithelial marker E-cadherin, while silencing of miR-218 lead to enhanced migration and invasion. In addition, we identified two novel miR-218 target genes that are associated with EMT including ZEB2, a zinc-finger transcription factor, and N-Cadherin, using reporter gene, RT-PCR and Western blot analysis. In our present study, we show that miR-218 is a direct suppressor of EMT by its ability to downregulate ZEB2 and N-Cadherin expression and represents an additional molecule contributing to the complexity of the EMT regulatory network. Citation Format: Jasmin Batliner, Mohammed Abba, Christine Hauser, Heike Allgayer. miR-218 suppresses invasion and migration via inhibition of ZEB2 and N-Cadherin in colon cancer. [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 4186. doi:10.1158/1538-7445.AM2013-4186
960 THE FXR AGONIST GW4064 INCREASES LIVER INJURY LEADING TO AN INHIBITION OF THE TRANSCRIPTIONAL ACTIVATION OF UGT1A GENES IN BILE DUCT LIGATED tgUGT1A WT MICE
Authors: A. Winkler, S. Kalthoff, N. Freiberg, M.P. Manns, C.P. Strassburg
Journal: Journal of Hepatology (2013)