tbuckley/cabot-search huggingface dataset:
Gene Targets of Insulin-Like Growth Factor-I Receptor (IGF-IR) Signaling and Their Potential Role in Breast Cancer.
Authors: A. Potter, A. Potter, A. Casa, A. Casa, A. Lee, A. Lee
Journal: Cancer Research (2009)

Abstract BACKGROUND: Insulin-like Growth Factor-I Receptor (IGF-IR) has been implicated in a number of human tumors including breast cancer. IGF-IR is over-expressed and potentially hyper-phosphorylated in breast cancer. The specific gene targets of the IGF-IR signaling pathway, and the role of these genes in the development and progression breast cancer is not known.METHODS: MCF7B breast caner cells, and MCF10A immortalized mammary epithelial cells were treated with either serum-free medium or serum-free medium plus 100 ng/ml IGF-I for 3 hours and 24 hours. RNA was isolated and hybridized to U133A Affymetrix microarrays. Candidate genes were selected based on fold change and p-value. Q-RT-PCR was used to validate expression of potential candidate genes. 5,6-Dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) was used (50µM) to block transcription. Cycloheximide (CHX) (20µg/mL) was used to block translation.RESULTS: Data from the microarray revealed 3673 and 3727 genes that were regulated by IGF-I treatment in MCF7B and MCF10A cells, respectively, at 3 hours. Various genes have been validated by Q-RT-PCR, and of these, Suppressor of Cytokine Signaling 2 (SOCS2) SOCS2 was repressed by IGF-I in MCF7B cells, but induced by IGF-I in MCF10A cells. The repression of SOCS2 by IGF-I was inhibited by pretreatment of MCF7B cells with a small molecule inhibitor of IGF-IR, but not by knockdown of IGF-IR by siRNA. This suggests that the repression of SOCS2 is specific to IGF-I signaling, but may be occurring through IGF-I stimulation of an alternate pathway other than IGF-IR. IGF-I doesn't alter levels of SOCS2 mRNA following blockade of transcription, suggesting that IGF-I does not have an effect on SOCS2 mRNA stability. Furthermore, IGF-I-mediated repression of SOCS2 does not require new protein synthesis, and is thus likely an immediate and direct response.CONCLUSION: SOCS2 is a candidate tumor suppressor gene in breast cancer, with loss of SOCS2 being related to cell proliferation and tumor growth. Here we show that SOCS2 is one of the gene targets of IGF-I signaling and is repressed by IGF-I stimulation in MCF7B breast cancer cells. Furthermore, the repression of SOCS2 by IGF-I appears to be via a direct inhibition of transcription. Together, this suggests that SOCS2 is a direct gene target of IGF-I signaling and that IGF-I repression of SOCS2 may be a crucial event that plays a role in driving the development or progression of breast cancer. Further studies are planned to determine how IGF-I affects SOCS2 function and the role of SOCS2 in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4167.
PAPEL DE LA ENDOSCOPIA EN EL DIAGNÓSTICO DE LA ENFERMEDAD INJERTO CONTRA HUÉSPED (EICH)
Authors: A Pereñiguez, E Sanchez Velasco, F Alberca De Las Parras, M Navalon Rubio, J Montserrat Coll, M Alajarin Cervera, A Serrano Jimenez, J Egea Valenzuela, R Jijón Crespín, LF Carballo Alvarez
Journal: Endoscopy (2014)

Introducción: La EICH es un proceso inflamatorio que afecta a pacientes sometidos a trasplante hematopoyético. La endoscopia se utiliza para valorar diagnóstico y extensión, permitiendo la toma de biopsias. Diseñamos un score diagnóstico que intenta estandarizar la técnica.
MicroRNA (miRNA) molecules as candidate regulators of Ro/SSA and La/SSB mRNA expression in Sjögren's syndrome
Authors: Vasiliki C Gourzi, Efstathia K Kapsogeorgou, Nikolaos C Kyriakidis, Ahsen Morva, Menelaos N Manoussakis, Haralampos M Moutsopoulos, Athanasios G Tzioufas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background-objectives</h3> Elevated in-situ mRNA expression of Ro/SSA and La/SSB autoantigens has been observed in the affected salivary glands (SG) of patients with Sjögren9s syndrome (SS); however, the regulatory mechanisms implicated in their expression are not defined. MicroRNAs (miRNAs) might be implicated in deregulated Ro/SSA and La/SSB in SS. Herein, the authors sought to investigate the expression of miRNAs that may target Ro/SSA and La/SSB ribonucleoproteins in SS. Therefore, the authors studied the expression of miRNAs, which are predicted to target Ro/SSA and La/SSB mRNAs, in salivary gland epithelial cells (SGEC), peripheral blood mononuclear cells (PBMC) and SG-tissues of SS patients and controls, as well as their association with respective mRNA expression. <h3>Materials-methods</h3> The prediction of miRNAs that target the Ro (Ro52/TRIM21 and Ro60/TROVE2) and La mRNAs was performed by miRecords database (http://mirecords.biolead.org). miRNAs and mRNAs expression was analysed in parallel by real-time PCR in total RNA from SGECs, PBMCs and SG-tissues obtained from 11 SS patients and 11 non-SS controls. Significant differences between SS patients and controls, and associations between miRNAs and mRNAs expression, were evaluated by non-parametric Mann–Whitney and Spearman9s rank correlation tests, respectively. <h3>Results</h3> The miRecords-computational analysis identified several miRNAs that target Ro52/TRIM21 (n=430), Ro60/TROVE2 (n=1258) and La/SSB (n=377) mRNAs. To narrow the number, the analysis was restricted to miRNAs that targeted both Ro/SSA (Ro52/TRIM21 and/or Ro60/TROVE2) and La/SSB mRNAs, and were identified by at least four databases. This approach identified 11 miRNAs (let-7b, miR-16, miR-129-5p, miR-153, miR-181a, miR-200b, miR-200b*, miR-223, miR-483-5p, miR-573, miR-583). Among them, miRs 129-5p, 153, 573 and 583 were not expressed in any of the samples studied and miR-200b* was not detected in PBMCs. The remainder were expressed in SGECs, PBMCs and SG-tissues. Compared to specimens derived from controls, those derived from SS patients manifested significant upregulation of miR-181a in SG tissues (p=0.02), miR-200b in SGECs (p=0.03) and miR-223 in PBMCs (p=0.02). miR-200b levels were negatively associated with Ro52/TRIM21 (r=−0.445, p=0.04), Ro60/TROVE2 (r=−0.454, p=0.04) and La/SSB mRNA expression only in SGECs (r=−0.495, p=0.02). <h3>Conclusions</h3> Our findings implicate miR-181a, miR-200b and miR-223 in SS, as well as miR-200b* in the regulation of Ro/SSA and La/SSB mRNAs. Further functional studies are needed to clarify the significance of the deregulated miRNAs in disease pathogenesis and autoantigen expression.
Therapeutic Effect of Propranolol on Paradoxical Hypertension after Repair of Coarctation of the Aorta
Authors: Samuel S. Gidding, Albert P. Rocchini, Robert Beekman, Cheryl A. Szpunar, Catherine Moorehead, Douglas Behrendt, Amnon Rosenthal
Journal: New England Journal of Medicine (1985)

Patients undergoing repair of coarctation of the aorta often have self-limited but severe hypertension in the first week after surgery (paradoxical hypertension). We conducted a controlled trial of treatment with propranolol before repair of coarctation of the aorta in 14 children to determine whether the drug would prevent paradoxical hypertension. Seven patients were randomly assigned to receive propranolol for two weeks before surgery and throughout the first postoperative week, and seven patients were assigned to receive standard postoperative care. Both groups had a similar significant (P<0.05) increase in the plasma norepinephrine level in response to surgery; however, when compared with no treatment, treatment with propranolol reduced not only the rise in systolic (P = 0.004) and diastolic (P = 0.003) blood pressure but also the postoperative increase in plasma renin activity (P<0.01). We conclude that prophylactic propranolol can prevent paradoxical hypertension and should therefore become a routine part of the operative care of patients with coarctation of the aorta. (N Engl J Med 1985; 312:1224–8.)
Distribution of BCL2 breakpoints in follicular lymphoma and correlation with clinical features: specific subtypes or same disease?
Authors: G Buchonnet, F Jardin, N Jean, P Bertrand, F Parmentier, S Tison, S Lepretre, N Contentin, P Lenain, A Stamatoullas-Bastard, H Tilly, C Bastard
Journal: Leukemia (2002)
Detection and Quantitation of Total and Allergen-Specific IgE in the Bronchial Mucosa of Atopic and Non-Atopic Asthmatics
Authors: Prathap Chellappan Pillai, Cailong Fang, Yih-Chih Chan, Mohamed H. Shamji, Clare Harper, Line Ohm-Laursen, Stephen R. Durham, Andrew Menzies-Gow, Raja Rajakulasingam, Ying Sun, Hannah J. Gould, Chris J. Corrigan
Journal: Journal of Allergy and Clinical Immunology (2013)
Abstract 680: Antitumor activity of CDDP and nuclear receptor PXR
Authors: Shuichi Kishimoto, Shoji Fukushima
Journal: Cancer Research (2011)

Abstract The goal of this study was to evaluate the effect of the possibility of compound that regulate the function of nuclear receptor as agent enhancing the activity of CDDP. Cell lines used in this study were HepG2 and some CDDP-resistant HepG2 cells that were established in our laboratory. These CDDP-resistant HepG2 cells show IC50 values several times higher than that of HegG2 cells. Changes in gene expression were assessed in RT-PCR assays, and the ability of apoptosis induction was assessed as caspase-3 activity. Gene expressions of nuclear receptors in HepG2 cells after exposure to CDDP were examined over time. Interestingly, IC90 dose of CDDP induced significant reduction in PXR mRNA expression with remarkable apoptosis, but IC50 dose of CDDP did no apoptosis and no significant change in PXR mRNA expression. Also, six established CDDP-resistant HepG2 cells show increased PXR mRNA expression relative to parent HepG2 cells. Therfore, PXR agonist and antagonist were used to elucidate if PXR could modulate the sensitivity of cells to CDDP. HepG2 cells exposured to PXR agonist rifampicin for 24 hr showed increased PXR mRNA expression. In HepG2 cells, pre-exposure to rifampicin followed by exposure to CDDP and coexposure to rifampicin and CDDP reduced induction of apoptosis compared to exposure to CDDP alone. Moreover, almost total suppression of apoptosis induced by CDDP was achieved by pre-exposure for 48 hr followed by coexposure to rifampicin for 24 hr. PXR antagonist leflunomide caused a slight enhancement in apoptosis induced by CDDP in HepG2 cells and a significant enhancement in apoptosis induced by CDDP in CDDP-resistant HepG2 cells. We concluded that nuclear receptor PXR is an important factor which regulates the expression of genes that affect on the antitumor activity of CDDP and that PXR antagonist can be a candidate as an agent augmenting the antitumor activity of CDDP. 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 680. doi:10.1158/1538-7445.AM2011-680
Case 33-2013
Authors: Feyza Marouf, Cosmas C. Giallourakis, Lee Baer, Michael S. Hanau, Barbara C. Holbert
Journal: New England Journal of Medicine (2013)

A 40-year-old woman was seen in the ED because of abdominal pain, anorexia, and weight loss. She said, “I think I have pancreatic cancer.” Physical examination, routine laboratory studies, and abdominal imaging were normal. Management decisions were made.
ESTUDIO PROSPECTIVO DE LA INCIDENCIA DE COMPLICACIONES ASOCIADAS A LA PUNCIÓN ASPIRATIVA CON AGUJA FINA GUIADA POR ULTRASONOGRAFÍA ENDOSCÓPICA (USE-PAAF) DE LESIONES QUÍSITCAS DE PÁNCREAS
Authors: A Rodríguez-D'Jesús, O Sendino, G Fernández-Esparrach, H Uchima, A Mena, J Albrecht-Bonomo, M Pellisé, G Martínez-Pallí, J Llach, A Ginès
Journal: Endoscopy (2011)

Introducción: La mayoría de estudios que evalúan las complicaciones de la USE-PAAF de lesiones quísticas del páncreas son retrospectivos o incluyen pocos pacientes, por lo que la incidencia real podría estar infravalorada.
Medical Library Service of College of Physicians and Surgeons of British Columbia
Authors: J DICK, W E HARRISON, C W FRASER, D H WILLIAMS
Journal: JAMA (1963)

A unique provincial medical library service has been established in British Columbia. Under the direction of professional librarians, the central library in Vancouver is building an extensive, largely clinical collection while 30 smaller branch libraries in hospitals throughout the province are establishing basic, up-to-date collections. Financial support comes from an annual fee of $25.00 per doctor paid to the College of Physicians and Surgeons of British Columbia. Photoduplication, mail and telephone services meet many reference needs. Reading is vital to continuing medical education. The library works closely with the University of British Columbia's Department of Continuing Medical Education to bring current medical knowledge to every doctor in British Columbia.
1273 OBESITY-INDUCED NAFLD: IDENTIFICATION OF TRANSCRIPTIONAL MASTER REGULATORS CONTROLLING METABOLIC AND INFLAMMATORY RESPONSES TO HIGH FAT DIET IN LIVER AND ADIPOSE TISSUE
Authors: W. Liang, G. Tonini, P. Mulder, M. van Erk, T. Kelder, A.M. van den Hoek, R. Mariman, P.Y. Wielinga, M. Baccini, A. Biggeri, R. Kleemann
Journal: Journal of Hepatology (2013)
SAT0491 Comparing the Power Doppler Modality of 5 Ultrasound Machines using a Microvessel Flow Phantom
Authors: D. F. Ten Cate, J. J. Luime, M. van der Ven, J. M. W Hazes, K. Kooiman, N. de Jong, J. G. Bosch
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS).[1-3] However, in our experience, PDUS may be highly dependent on machine type. To clarify how the PDUS signal differs between machines a flow phantom could be used. <h3>Objectives</h3> Determine the lowest flow that the power Doppler (PD) modality of 5 US machines could detect by creating a small microvessel (150micron) flow phantom. <h3>Methods</h3> The flow phantom, consisted of an acrylic (PMMA) container filled with tissue mimicking material(TMM)[4], with three microvessels (2000 micron, 1000 micron and 150 micron). The blood mimicking fluid was based on the recipe by Ramnarine.[5] A syringe pump (Harvard Apparatus Pump 11 Elite) was used to generate different flows. Five US machines were used, the Esaote MyLab60 (probe LA 435), Aloka α7 (UST-5411), Philips iU22 (L9-3), Ultrasonix SonixTouch (L14-5/38) and VisualSonics Vevo2100 (MS200). Settings were optimised to detect lowest flows by adjusting pulse repetition frequency, velocity range, filters, frequency and gain. We recorded the lowest possible flow in each of the vessels that still resulted in a continuous PDUS signal for each machine. Flow velocities were calculated from pump flow setting and microvessel diameter. <h3>Results</h3> <h3>Conclusions</h3> PD was highly variable between machines. The Esaote detected the lowest flow. The very low flow detected by the Esaote in the 2mm vessel was checked multiple times by multiple observers. The machines predominantly used in research (Ultrasonix, VisualSonics) were not able to detect flows in the smallest vessel (150 micron). The differences found between the machines are apparently caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Probe frequency does not explain the large differences found. A spurious finding was that the minimal detectable flow velocity was lower in the 1mm vessel than in the 2mm vessel. Possibly, the 1mm vessel was compressed by the TMM so that the calculated flow velocity was underestimated. The relative differences between machines are unchanged by this. For a reliable and reproducible detection of microvessel flow in inflamed joints, the choice of the US machine and its settings seems very important. By investigating the flow velocity of blood in an inflamed joint, the minimal flows that rheumatological US machines need to detect will be known. Then, our flow phantom would be a very useful instrument in the process of optimising US machines and for rheumatologists when buying a new US machine. <h3>References</h3> Peluso (2011) Ann Rheum Dis Saleem (2011) Ann Rheum Dis Brown (2008) Arthritis Rheum Teirlinck (1998) Ultrasonics Ramnarine (1998) Ultrasound Med Biol <h3>Disclosure of Interest</h3> None Declared
Abstract B50: Smurf2-deficient mice exhibit increased tumorigenesis
Authors: Charusheila Ramkumar, Hong Zhang
Journal: Cancer Research (2009)

Abstract Smurf2, a HECT family E3 ubiquitin ligase has been shown to ubiquitinate and target for degradation several proteins that promote tumorigenesis, including TGF-β receptors, Smad2/3, β-catenin, and Mad2. Furthermore, we have found previously that Smurf2 can induce senescence in early passage cells in culture. As senescence has been postulated to act as a tumor suppression mechanism, we hypothesized that Smurf2 functions as a tumor suppressor. To test this hypothesis, we generated a Smurf2-deficienct mouse strain using a gene trapping strategy. The homozygous Smurf2-deficient mice were obtained with the expected Mendelian ratio after intercrossing of heterozygous mice, and they exhibited no obvious developmental defects. Analysis of mouse embryonic fibroblasts from these Smurf2-deficient mice revealed that they exhibited delayed senescence entry and consequently had an increased tendency to immortalize in culture. Cohorts of Smurf2-deficient and wild-type mice were monitored for spontaneous tumor development. In this ongoing study, 20% (7 out of 35) of the Smurf2-deficient mice, but none of the wild-type mice showed signs of morbidity after 14-months of age. The moribund Smurf2-deficient mice were found to have enlarged spleen, pale kidneys and liver, and/or enlarged lymph nodes. Histopathology analysis indicated that most of the tumors are lymphomas. In addition, we found adenocarcinoma of the intestine in one Smurf2-deficient mouse. Collectively, our data suggest that Smurf2 is a tumor suppressor. The investigation of the mechanism by which Smurf2 deficiency leads to tumorigenesis is ongoing. Citation Information: Cancer Res 2009;69(23 Suppl):B50.
Abstract 11855: CSL112, a Novel Formulation of Human Apolipoprotein A-I, Dramatically Increases Cholesterol Efflux Capacity in Healthy Subjects: A, Placebo-Controlled, Double-Blinded, Randomized Single Ascending Dose Study
Authors: Andreas Gille, Rachael Easton, Samuel Wright, Charles Shear
Journal: Circulation (2012)

Introduction: The ability of HDL to efflux cholesterol from atherosclerotic plaque is thought to underpin its potential for cardioprotection. CSL112 is apoA-I, the active component of HDL, purified...
Abstract ADV08: Bridging the gaps in service.
Authors: Mary Kay Dauria
Journal: Cancer Research (2013)

Abstract Susan's Rally is a Houston based 501c3 organization that started as a group supporting breast cancer research and has expanded to support services provided for those with all types of cancer. What began as a fun road rally for Bruce and Susan Roberson morphed into a fun-raising event for cancer after Susan was taken by breast cancer. For 17 years, Bruce and his friends have continued the rally in her honor and now the proceeds from the rally, golf tournament, and auctions are used to fight the disease and assist with providing patients support services. Susan's Rally has raised over a million dollars in cash and in-kind donations utilizing all volunteer labor. Except for a few office supplies, postage and printing, all of Susan's Rally dollars go to fight cancer and support patients. Some of the programs supported included MD Anderson Patients Support Network, research at the Christus Stehlin Foundation for Cancer Research, provide diagnostic imaging for uninsured women at The Rose, counseling at Y-Me, and assists with making available low-cost short-term housing at The Sojourn House-Apartment, homes for cancer patients. In 2012 Susan's Rally also began funding “Dia De la Mujer community health festivals providing free breast exams, HIV testing an pap smears for women in need. Citation Format: Mary Kay Dauria. Bridging the gaps in service. [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 ADV08. doi:10.1158/1538-7445.AM2013-ADV08
FRI0309 The genome-wide expression of human osteoarthritic cartilage shows different GENE-expression profiles OA-related
Authors: J. Fernandez-Tajes, A. Soto-Hermida, M. Fernandez-Moreno, M.E. Vazquez-Mosquera, N. Oreiro, C. Fernandez-Lopez, E. Cortes-Pereira, S. Fernandez-Relaño, I. Rego-Perez, F.J. Blanco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Many genes, many of them still unknown, are involved in the etiology and development of OA. Today, different tools are available to try to identify some of the key genes related to the OA process. <h3>Objectives</h3> To perform a genome-wide expression assay in order to identify different expression profiles in the OA disease <h3>Methods</h3> Total RNA from OA cartilage samples was isolated with RNeasy Kit (Qiagen, Madrin, Spain) following manufacturer's instructions. RNA was checked for integrity and purity with the Agilent Bioanalyzer (Agilent Technologies) and NanoDrop spectrophotometer (Thermo Scientific). 150 nanograms of total RNA were used for cDNA synthesis using the Ambion WT Expression kit (Ambion). The fragmented cDNA was hybridized against the Human Gene 1.1 ST array strip (Affymetrix) and scanned using the GeneTitan system (Affymetrix). Quality controls, normalization, pre-processing, differential gene expression and functional analyses were carried out with Bioconductor packages using R software. <h3>Results</h3> Human Gene 1.1 ST Array, which interrogates more than 28,000 well-annotated genes of 33,297 probes, was used for studying the genome wide expression profile of 23 OA-patients tissue samples. A non-specific filtering was previously applied for removing those probes with non-annotation information and with low intra-array variation. An unsupervised machine learning approach revealed a group of samples highly different (Figure 1). The differential expression analysis between this cluster, comprising a total of five OA-patients, and the rest of the samples allowed for the identification of 176 differentially expressed probes with an adjusted <i>p value</i> below 0.0001. The 20 differentially expressed probes with higher log Fold Change are presented in Table 1. The analysis of the biological processes related to these differentially expressed genes showed that inflammation and immune processes were the main pathways found to be altered when a gene set enrichment analysis was applied. <h3>Conclusions</h3> The genome-wide expression analysis shows a clearly distinct profile for a group of OA patients. Both inflammation and immune response processes appeared to be altered and therefore are revealed as key factors in the development of the OA disease. <h3>Disclosure of Interest</h3> None Declared