tbuckley/cabot-search huggingface dataset:
GE-39 * VALIDATION OF GLIOMA SPHERE-FORMING CELLS AS MODELS OF GLIOBLASTOMA AND IDENTIFICATION OF NOVEL DRIVERS OF TUMORIGENESIS THROUGH COMPREHENSIVE GENOMIC CHARACTERIZATION
Authors: Q. Wang, R. Ezhilarasan, S. Zheng, J. Gumin, T. Heffernan, G. Draetta, F. Lang, R. Verhaak, E. Sulman
Journal: Neuro-Oncology (2014)

Glioma sphere-forming cells (GSCs) play important roles in tumor maintenance and chemotherapy and radiation resistance, and thus serve as important models for the development of novel therapies and for understanding tumor biology. We hypothesized that genomic analyses of GSCs in the absence of normal stroma would identify novel somatic alterations not previously reported from whole tumor specimen analyses. We analyzed 42 GSCs, derived at the time of surgical resection, and their matched tumors of origin. Unsupervised consensus clustering by non-negative matrix factorization (CNMF) using whole transcriptome sequencing data identified 5 transcriptional classes. Comparison to published TCGA GBM subtypes using single-sample gene set enrichment analysis (ssGSEA) showed that 9 GSCs perfectly matched with TCGA mesenchymal subtype. The other 4 subgroups of GSCs mapped to proneural and/or classical subtypes, while none of the GSC classes matched with the neural TCGA subtype. Overall, 73% of GSCs matched the TCGA subtype of paried tumor, suggesting transcriptional consistency between GSCs and their parental tumor. A total of 88 candidate gene fusions were also identified in the GSCs, including the previously reported FGFR3-TACC3 and EGFR-SEP14 fusions. DNA copy number analysis indicated recurrent regions of frequent loss or gain, such as EGFR, MYC, and MYCN amplification, and deletion of PTEN and CDKN2A. Whole exome sequencing based analysis identified 3,918 somatic mutations in 22 GSCs. PTEN, TP53, EGFR and 17 additional genes were identified as significantly altered. Our results indicate genomic consistency between GSCs and their tumors of origin, suggesting the suitability of GSCs as a model for preclinical testing. Additional gene fusions and somatic mutations were detected in GSCs suggesting the important role of these cell models in identifying infrequent events only detectable in pure tumor cell populations.
Comparison of Tc-99m HIG and Three-Phase Tc-99m MDP Bone Scintigraphy for Evaluating the Efficacy of Yttrium-90 Silicate Radionuclide Synovectomy
Authors: Esra Arzu Gencoglu, Gulseren Aras, Ozlem Kucuk, Gulay Atay, Ibrahim Tutak, Sebnem Ataman, Ayfer Soylu, Erkan Ibis
Journal: Clinical Nuclear Medicine (2003)

Purpose The aim of this study was to compare Tc-99m human immunoglobulin (HIG) and three-phase Tc-99m MDP bone scintigraphy for the assessment of the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis. Materials and Methods Fifteen patients with rheumatoid arthritis and chronic persistent synovitis in 23 knee joints had radionuclide synovectomy with Y-90 silicate. The patients underwent imaging before and 3, 6, 9, and 12 months after therapy using clinical evaluation, Tc-99m HIG scintigraphy, and three-phase Tc-99m MDP bone scintigraphy. Results In the 13 of 23 knee joints that showed successful clinical results with Y-90 therapy, the Tc-99m HIG index values obtained 3 months after radionuclide synovectomy were significantly lower than the pretreatment index values (P < 0.001). In the same 13 joints, the Tc-99m MDP index values (in the blood-pool and delayed phases) before and 3 months after therapy were statistically similar. Six months after injection, these values were significantly lower in both the blood-pool (P < 0.001) and late (P < 0.05) phases in all 13 joints. In the other 10 of 23 knee joints that did not respond to treatment, the Tc-99m MDP and Tc-99m HIG index values were statistically similar before and after Y-90 therapy. Conclusions Based on these findings, Tc-99m HIG scintigraphy appears to be a valuable method that complements clinical assessment of the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis, starting in the early post-treatment period. However, three-phase Tc-99m MDP bone scintigraphy may be valuable in the late postsynovectomy period.
Absence of Serum Gamma Globulins in an Adult
Authors: Jay P. Sanford, Cutting B. Favour, Melvin S. Tribeman
Journal: New England Journal of Medicine (1954)

THE syndrome of low serum gamma globulin in the presence of relatively normal quantities of the other protein factors has recently been described in children, but has not heretofore been observed in adults. The first case of "agammaglobulinemia" was reported by Bruton1 in a boy who, between the ages of four and a half and eight years, had 18 bouts of sepsis with 8 different types of pneumococci isolated, 5 episodes of otitis media, and 3 attacks of epidemic parotitis. Prophylactic antibacterial therapy was not always successful in preventing reinfection. After autogenous pneumococcal vaccine, typhoid vaccine and diphtheria immunization, no . . .
Stability of HER-2/neu Expression Over Time and at Multiple Metastatic Sites
Authors: G A Niehans, T P Singleton, D Dykoski, D T Kiang
Journal: JNCI Journal of the National Cancer Institute (1993)

Amplification and over-expression of the HER-2/neu oncogene (also known as c-erbB-2) occurs in 20%-30% of invasive breast carcinomas. The extent to which HER-2/neu expression changes over time in association with tumor progression or is heterogeneous at different metastatic sites has received only limited study.Our purpose was to determine whether primary tumors differ from metastases in HER-2/neu protein content or whether metastases are heterogeneous in regard to HER-2/neu expression.In a retrospective study, we examined tumor tissue obtained at autopsy from two to five metastatic organ sites in each of 30 patients who died with metastatic breast carcinoma. Using an immunoperoxidase technique, we stained archival formalin-fixed, paraffin-embedded tissue sections with a monoclonal antibody to the 185-kilodalton protein product (p185) of the HER-2/neu gene.The tissue from eight of 30 patients showed strong diffuse reactivity for p185 at all metastatic sites examined. Tissues from six patients showed faint staining and tissues from 15 were negative, again with a congruent staining pattern. A single case showed discordant staining, in that two of four metastases showed faint staining, whereas the other two showed strong immunoreactivity. In 14 cases, we were able to obtain paraffin blocks from the original biopsy or surgical resection of the primary breast lesion. For these 14 patients, the average length of time between initial diagnosis and death was 4 years (range, 2-9). There was good correlation between results from autopsy and original surgical tissues.Expression of HER-2/neu appears to be relatively stable over time and is generally congruent at different metastatic sites.The fact that p185 immunoreactivity is rarely heterogeneous is encouraging, both for the potential use of HER-2/neu-related proteins as serum tumor markers and for innovative therapies targeted at p185 expression.
Is the Upright Position More Sensitive Than the Supine Position in Breast Cancer Sentinel Node Lymphoscintigraphy?
Authors: ANNE PIERINI, HOWARD J. DWORKIN
Journal: Clinical Nuclear Medicine (2001)

The authors compared the supine and standing positions for lymphoscintigraphy in breast cancer patients to identify any changes in the number of affected lymph nodes detected and the quality of images.Twenty-three patients were examined using lymphoscintigraphy in both positions. Sequential supine, standing, and supine oblique images were acquired in each patient.The number of lymph nodes detected or the quality of the images acquired was improved in 20 of the 23 patients in the standing position compared with the supine position. The remaining three patients' images were judged to be equal in lymph node number and image quality in both positions.Lymphoscintigraphy in patients with breast cancer appears to be more sensitive in the standing than in the supine position.
Abstract 4752: Selective inhibition of cancer metastasis with a novel small therapeutic molecule
Authors: Li Xu, Rebecca Farmer, Xiaoke Huang, Sean Pruell, Eric Voll, Janet Pavese, Matias Valsecchi, Margaret Biddle, Antoinette Nibbs, Michael Avram, Karl A. Scheidt, Raymond C. Bergan
Journal: Cancer Research (2012)

Abstract Prostate cancer (PCa) is the second most common cause of cancer death in US males. Death is typically caused by metastasis. Naturally occurring isoflavanones have been reported to be a class of compounds that effectively inhibit PCa motility and metastasis. This led us to use these compounds as a synthetic scaffold starting point. By integrating fragment-based diversification synthesis with chemi-driven biological selection, we discovered novel small molecule therapeutics with increased selectivity and potent efficacy. We thereby efficiently synthesized a new class of bioactive compounds that inhibit cell motility in vitro and inhibit human PCa metastasis in a murine model at low nanomolar concentrations. Extensive investigations indicate high specificity at the molecular and cellular levels, and failed to identify toxicity, even at high doses administered over extended periods. Importantly, efficacy against several cancer types was also demonstrated. Target validation studies used our lead as a chemical probe, and point to inhibition of ATM/ATR interaction with specific substrate proteins as important. Together, these studies indicate that we have successfully discovered a novel compound, acting upon a novel pharmacologic target, which selectively inhibits human PCa metastasis. Taken with our favorable preclinical toxicological data, these findings support movement of our lead compound into early phase human trials. 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 4752. doi:1538-7445.AM2012-4752
AB0324 Physical Activity in Patients with Rheumatoid Arthritis
Authors: S. El Kabbaj, F. Allali, I. Ben Slama, T. Lakhdar, L. Medrare, A. Ngeuleu, H. Rkain, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The purpose of this study was to identify physical activity behaviors of Moroccan patients with RA and her associations with RA demographic and disease related variables. <h3>Methods</h3> A cross sectional study was conducted in 103 RA. Socio-demographic characteristics and Disease specific variables were documented. Disease activity was measured with Disease Activity Score 28 (DAS28), quality of life was assessed with rheumatoid arthritis impact disease (RAID), fatigue was evaluated by fatigue Visual Analogic scale and Health Assessment Questionnaire (HAQ) was completed by all patients. Physical activity was evaluated with the Arab version of the International Physical Activity Questionnaire (IPAQ) short version. <h3>Results</h3> A total of 90 women and 13 men with RA participated in this study. Mean age of participants was 49.7±11.4.disease duration was a median of 8.16 years [3,25-14,16]. Total amount of physical activity was a median of 1873 (346-4053) MET-minute/week. However in 30.8% the physical activity was low. In univariate analysis lower physical activity (IPAQ) correlated with higher disease activity (OR=-3.9; CI95%&gt;899–300; p&lt;0,001); poor functional capacity (OR=-4.5; CI95%&gt;2146–845; p=&lt;0.001); higher fatigue levels (OR=-2.3; CI95%&gt;43.4–3.3; p=0,02) and low quality of life (RAID) (OR=-2.8; CI95%&gt;610–107p=0,006). No relationship was found between PA, age, disease duration and BMI. After multivariate analysis HAQ (OR=-3.1; CI95%&gt;991–85; p=0.002) and DAS28 (OR=-3.1;CI95%&gt;2587–606) still strongly associated with PA. <h3>Conclusions</h3> This study suggested that lower physical activity associated with high disease activity and poor functional capacity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5826
Case 23-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, B.D.T. Daly, E.J. Mark
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 25-year-old woman was admitted to the hospital because of an opaque lesion in the right lung.The patient was well until 17 months earlier, when wheezing developed and did not respond to medical measures. An x-ray film of the chest showed a right hilar mass with collapse of the right upper lobe. Bronchoscopic examination confirmed the presence of a mass within the right mainstem bronchus, and microscopical examination of a biopsy specimen showed a carcinoid tumor. Computed tomographic (CT) scans of the thorax and abdomen, a radionuclide bone scan, and microscopical examination of a needle-biopsy specimen . . .
EFFECT OF SELEXIPAG ON MORBIDITY/MORTALITY IN PULMONARY ARTERIAL HYPERTENSION: RESULTS OF THE GRIPHON STUDY
Authors: Vallerie V. McLaughlin, Richard Channick, Kelly Chin, Aline Frey, Sean Gaine, Ardeschir Ghofrani, Marius Hoeper, Irene Lang, Ralph Preiss, Lewis J. Rubin, Gérald Simonneau, Olivier Sitbon, Mylène Stefani, Victor Tapson, Nazzareno Galiè
Journal: Journal of the American College of Cardiology (2015)
Abstract 3020: The role of NF-κB (p65) and Stat3 interplay in the regulation of radiation-induced, ICAM-1-mediated migration and invasion in glioma
Authors: Divya Kesanakurti, Dilip Maddirela, Chandramu Chetty, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Aberrant activation of both NF-κB and Stat3 is associated with enhanced tumor metastasis in various cancers. In human glioma xenograft cells 4910 and 5310, irradiation (IR; 8 Gy) elevated Stat3 and p65 phosphorylation and persistent nuclear translocation in correlation with massive increases in cellular and soluble ICAM-1 levels. Co-immunoprecipitation experiments confirmed enhanced nuclear phospho-p65/phospho-Stat3 and acetyl-p65/phospho-Stat3 interactions along with enhanced invasiveness and migration in IR-treated cells. Promoter analysis indicated presence of adjacent NF-κB- and Stat3-consensus binding elements in the proximal promoter and the proximal intron-1 of the ICAM-1 promoter, whereas overlapping NF-κB/Stat3 binding motifs were identified in the distal intron-1 region. ChIP binding and promoter/luciferase reporter assays showed that IR induced prominent binding of both Stat3 and NF-κB to the proximal intron-1 region followed by the distal intron-1 and the proximal promoter regions on the ICAM-1 gene. Individual treatments with Stat3.si or JSH-23 blocked the occupancy of both Stat3 and p65 onto the ICAM-1 promoter and prevented subsequent ICAM-1-mediated migration and invasion. In addition, constitutive activation of Stat3 and NF-κB by Stat3C or TNF-α significantly elevated IR-induced migration and invasion. In vivo orthotropic experiments in nude mice showed that the Stat3.si treatment reduced tumor growth and IR-induced phopsho-Stat3/phospho-p65 and ICAM-1 expression when compared to pSV-treated controls. These results suggest that both p65 and Stat3 bind to the intronic region of ICAM-1 promoter to induce its optimal transcription in IR-treated cells and abrogation of IR-induced p65/Stat3 binding inhibits ICAM-1-mediated enhancement of malignancy in post-irradiated tumor cells. As such, the results of this study clearly have potential future therapeutic significance in glioma treatment. 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 3020. doi:1538-7445.AM2012-3020
Former Tory health minister posts message of support for junior doctors
Authors: Abi Rimmer
Journal: BMJ (2015)

A former Conservative health minister has expressed support for junior doctors who are protesting against proposed changes to their contracts.

In a video posted on YouTube (https://www.youtube.com/watch?v=PXCgNAkGnWg&feature=youtu.be), Dan Poulter said that a new contract for junior doctors in England needed to properly reward doctors for the work that they did. The message came ahead of protests organised by junior doctors on Saturday 17 October in London, Nottingham, and Belfast against proposed changes to their contract. Poulter, who is still a Conservative MP, …
Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis
Authors: Robert N. Foley, David T. Gilbertson, Thomas Murray, Allan J. Collins
Journal: New England Journal of Medicine (2011)

Patients with end-stage renal disease requiring dialysis have limited tolerance of metabolic and volume-related deviations from normal ranges; in addition, the prevalence of cardiovascular disease is high among such patients. Given these problems, we hypothesized that a long interdialytic interval is associated with adverse events in patients receiving hemodialysis.We studied 32,065 participants in the End-Stage Renal Disease Clinical Performance Measures Project, a nationally representative sample of U.S. patients receiving hemodialysis three times weekly, at the end of calendar years 2004 through 2007. We compared rates of death and cardiovascular-related hospital admissions on the day after the long (2-day) interdialytic interval with rates on other days.The mean age of the cohort was 62.2 years; 24.2% of the patients had been receiving dialysis treatment for 1 year or less. Over a mean follow-up interval of 2.2 years, the following event rates were higher on the day after the long interval than on other days: all-cause mortality (22.1 vs. 18.0 deaths per 100 person-years, P<0.001), mortality from cardiac causes (10.2 vs. 7.5, P<0.001), infection-related mortality (2.5 vs. 2.1, P = 0.007), mortality from cardiac arrest (1.3 vs. 1.0, P = 0.004), mortality from myocardial infarction (6.3 vs. 4.4, P<0.001), and admissions for myocardial infarction (6.3 vs. 3.9, P<0.001), congestive heart failure (29.9 vs. 16.9, P<0.001), stroke (4.7 vs. 3.1, P<0.001), dysrhythmia (20.9 vs. 11.0, P<0.001), and any cardiovascular event (44.2 vs. 19.7, P<0.001).The long (2-day) interdialytic interval is a time of heightened risk among patients receiving hemodialysis. (Funded by the National Institutes of Health.).
Utilisation et efficacité de l'erythromycine avant une endoscopie pour hémorragie digestive haute: résultats de l'observatoire des hémorragies digestives hautes de l'ANGH
Authors: S Nahon, EA Pariente, P Lahmek, I Rosa Hezode, R Faroux, J Henrion, AJ Remy, A Pauwels, A Boruchowicz, B Nalet, B Lesgourgues, RL Vitte
Journal: Endoscopy (2011)

Introduction: la réalisation en urgence d'une endoscopie digestive est la règle au cours des hémorragies digestives hautes (HDH). Afin d'améliorer l'efficacité de l'endoscopie, l'administration d'érythromycine par voie intraveineuse est préconisée 1. Le but de notre étude a été d'évaluer les pratiques concernant l'administration et l'efficacité de l'érythromycine à travers l'observatoire de l'ANGH sur les HDH.
Diagnosis of Brain Infarction on Lung Perfusion Scintigraphy
Authors: M Onur Demirkol, B Mutlu, B Say, Y Başaran, F Turan
Journal: Clinical Nuclear Medicine (2001)

ONUR DEMIRKOL, MEHMET M.D.,*; MUTLU, BÜLENT M.D.,†; SAY, BIROL,†; BAŞARAN, YELDA M.D.†; TURAN, FIKRET M.D.†Author Information
Abstract 1426: Identification of secretory stromal gene signature of the ovarian tumor microenvironment and implications for ovarian cancer progression
Authors: Melissa S. Thompson, Lina Albitar, Sue Ghosh, Kwong-Kwok Wong, William R. Welch, Michael J. Birrer, Samuel C. Mok
Journal: Cancer Research (2010)

Abstract Ovarian cancer the deadliest gynecologic disease and despite the significant role of the tumor-associated stroma in cancer progression, little research has been done on the specific role of the tumor-associated stromal microenvironment on ovarian cancer progression. Our objective was to identify genes that are differentially regulated in the stromal component of high-grade late-stage serous ovarian cancer and illustrate direct and specific effects of their differential expression on ovarian cancer progression. Microarray analysis performed on RNA isolated from 10 microdissected normal ovarian fibroblasts, and the epithelial and stromal component of 16 high-grade late stage serous ovarian cancers revealed more than 40 secreted proteins that are overexpressed more than 5 fold by cancer-associated fibroblasts (CAFs) exclusively. Quantitative RT-PCR validated the overexpression of several genes, including sFRP2, by the CAFs. Clinical data correlated stromal sFRP2 overexpression with poorer overall survival and chemoresistance in patients with high-grade late stage serous ovarian cancer, suggesting that sFRP2 promotes ovarian cancer progression. In vitro functional studies illustrate increased ovarian cancer cell proliferation rates in response to recombinant sFRP2 as well as CAF-conditioned medium and pathway analysis via transcription-reporter assays revealed that recombinant sFRP2 signals through the NFκB and Wnt pathways in ovarian cancer cells, both of which affect cell growth. While not affecting cell proliferation, recombinant sFRP2 increased endothelial signaling to the NFAT pathway, which affects endothelial tubal branching. These results were corroborated in vivo such that microenvironments expressing higher levels of sFRP2 exhibited significantly higher microvessel density compared with microenvironments with lower sFRP2 expression. Our results illustrate a direct and specific signaling linkage from the tumor microenvironment to tumor cells and endothelial cells that contributes to tumor progression. In this case, sFRP2 exhibited significant influence on characteristics of tumor progression (i.e. tumor proliferation, microvessel morphology) suggesting that other differentially expressed genes identified by the microarray in CAFs may also play significant roles in this process. 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 1426.