tbuckley/cabot-search huggingface dataset:
NME1 Protein Expression and Loss of Heterozygosity Mutations in Primary Human Breast Tumors
Authors: C. S. Cropp, R. Lidereau, A. Leone, D. Liscia, A. P. M. Cappa, G. Campbell, E. Barker, V. Le Doussal, P. S. Steeg, R. Callahan
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article NME1 Protein Expression and Loss of Heterozygosity Mutations in Primary Human Breast Tumors Get access Craig S. Cropp, Craig S. Cropp Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosette Lidereau, Rosette Lidereau Institut National de la Santé et de la Recherche Médicale, Centre René Huguenin, St. CloudFrance Search for other works by this author on: Oxford Academic PubMed Google Scholar Alvaro Leone, Alvaro Leone Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Liscia, Daniel Liscia S. Giovanni Hospital, TorinoItaly Search for other works by this author on: Oxford Academic PubMed Google Scholar A. P. M. Cappa, A. P. M. Cappa S. Giovanni Hospital, TorinoItaly Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory Campbell, Gregory Campbell National Institute of Neurologic Disorders and StrokeBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward Barker, Edward Barker Oncogenetics, PhoenixAriz Search for other works by this author on: Oxford Academic PubMed Google Scholar Viviane Le Doussal, Viviane Le Doussal Institut National de la Santé et de la Recherche Médicale, Centre René Huguenin, St. CloudFrance Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia S. Steeg, Patricia S. Steeg Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Callahan Robert Callahan Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, Md Correspondence to : Robert Callahan, M.D., National Institutes of Health, Bldg. 10, Rm. 5B50, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 15, 3 August 1994, Pages 1167–1169, https://doi.org/10.1093/jnci/86.15.1167 Published: 03 August 1994 Article history Received: 29 October 1993 Revision received: 02 April 1994 Accepted: 23 May 1994 Published: 03 August 1994
England and Wales finally get first chief coroner
Authors: C. Dyer
Journal: BMJ (2012)

Peter Thornton, the Old Bailey judge who presided over the inquest into the death of the newspaper seller Ian Tomlinson during the G20 protests in 2009,1 will become the first chief coroner for England and Wales next September.

Thornton was appointed to the post by the lord chief justice in 2010 but had not taken up his duties when the newly elected coalition government proposed to scrap the role in its cost cutting “bonfire of the quangos.” However, campaigning groups persuaded it to relent. …
Open-label, non-randomized, multicenter phase II study evaluating the angiogenesis inhibitor PTK787/ ZK222584 (PTK/ZK) in patients with advanced neuroendocrine carcinomas (NEC)
Authors: M. E. Pavel, C. Bartel, F. Heuck, F. Neumann, N. Tiling, U. F. Pape, U. Plöckinger, B. Wiedenmann
Journal: Journal of Clinical Oncology (2008)

14684 Background: Vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) are important mediators of tumor growth and metastasis. Since NEC of the gastroenteropancreatic system are highly vascularized and strongly express VEGF and its receptors, anti-VEGF receptor therapy should be a promising approach. PTK/ZK (Bayer Schering Pharma and Novartis Pharma) is an oral angiogenesis inhibitor which selectively blocks VEGF receptor tyrosine kinase signaling from all known VEGFRs. Methods: Patients (pts) with histologically confirmed NEC (proliferation index Ki67< 15%) non-surgically curable and progressive within 6 months according to RECIST criteria were included in an open label, non-randomized multicenter phase II study. All pts were treated daily with an oral dose of 1250 mg of PTK/ZK. In case of drug related adverse events (AE) the dose could be reduced. The primary endpoint was the overall response rate according to RECIST. Secondary endpoints were time to progression (TTP), survival time, WHO performance status, quality of life, toxicity and safety. Results: A total of 20 pts (10 male, 10 female) with a median age of 61 years (range 37 to 72) were enrolled between 8/2005 and 11/2007. 3 pts stopped treatment early for side effects. 17 pts were evaluable for tumor response. Primary tumors were located in the pancreas in 4, midgut in 7, hindgut in 3, in the lung in 1 and were unknown in 2 patients); 4 pts were treated simultaneously with somatostatin analogues. Best response was stable disease in 8/16 pts at 6 months (50%) and 4/15 pts at 12 months (27%). 2 pts have not yet reached the 12 months time line. Median TTP was 7 months (3–23 months), with 3 pts have not yet reached TTP (after 18, 12 and 6 months). Altogether 7 pts stopped PTK/ZK for treatment related AEs (dizziness, nausea, emesis, hypertension, proteinuria). Conclusions: PTK/ZK has some antiproliferative activity in pts with advanced NEC with a relatively high rate of disease stabilisation. The compound was well tolerated in the majority of the pts. Antiangiogenic therapies should be further evaluated in neuroendocrine tumor pts, preferably in combination with cytotoxic treatment modalities. No significant financial relationships to disclose.
A3.22 IL-6 trans signalling drives collagen via an epigenetic mechanism mediated through SMAD3
Authors: Steven O’Reilly, Marzena Chiechomska, Jacob M van Laar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic sclerosis is an autoimmune condition of unknown aetiology. The disease consists of autoimmunity, vascular disease, inflammation and ultimately fibrosis. It is characterised by accumulation of an excessive amount of extracellular matrix molecules that primarily include collagen type I. IL-6 is a profibrotic cytokine that is elevated in the autoimmune condition systemic sclerosis and is known to induce collagen I expression but the mechanism (s) behind this induction are currently unknown. <h3>Methods</h3> Dermal fibroblasts were isolated from biopsies from healthy donors and SSc patients and treated with IL-6&amp;sIL-6R in vitro in serum free media. Collagen was analysed using qRT-PCR and siRNA was employed for STAT3 and SMAD3 silencing. MicroRNA was analysed using specific primers and normalised to SNORD. <h3>Results:</h3> Using healthy dermal fibroblasts in vitro we analysed the signalling pathways that underscore the IL-6 mediated induction of collagen. We show that IL-6 trans signalling is important and that the effect is dependent on Signal Transducer and Activator of Transcription 3 (STAT3), however the effect is indirect and mediated through enhanced TGF-β signalling and the classic downstream mediator Smad3 as silencing abrogated the effect. This induces collagen expression through the repression of the expression of the fibrotic microRNA (miR) 29a as collagen I is its bona fide target gene. Transfection of miR29a mimics reverses the diseased collagen overexpression in SSc fibroblasts. <h3>Conclusion</h3> IL-6 is driving the fibrosis through STAT3 and SMAD-mediated mechanisms that repress miR29a and thus upregulate collagen. Strategies that block IL-6 signalling will cause derepression of miR29a and normalisation of collagen levels.
PWE-134 Outcomes For Liver Disease Patients Admitted to a District General Hospital: Abstract PWE- Table 1
Authors: S Paranahewa, L Allen, C Toms, A Lalloo, V Kulhalli, M Guinane, A Rochford, A Dias
Journal: Gut (2013)

<h3>Introduction</h3> In the UK, liver disease is the 5<sup>th</sup> commonest cause of death. A recent BSG commissioning report states that there were 43,694 hospital episodes due to liver disease with a mortality rate of 15.5% and median age of death of 59<sup>1</sup>. The guidelines recommend that all liver disease should be managed by a hepatologist. Newham University Hospital (NUH) serves a socially deprived and ethnically diverse population of 290,000. <h3>Methods</h3> All patients with a primary diagnosis of liver disease admitted to NUH from 1 April 2012 to 31 October 2012 were included in this study. Patients were identified from the on-call admission lists and electronic patient records and admission notes were checked for suitability. Patients admitted with alcohol withdrawal but without underlying liver disease were excluded. We examined the outcomes of all liver patients admitted during this time period. <h3>Results</h3> 78 patients were admitted, of which 9 had ≥2 admissions. The demographic data and outcomes are listed in Table 1. The ethnic variation reflected that of the local community. The main causes of liver disease were alcoholic liver disease (56%), viral hepatitis (22%) and drug-induced hepatitis (12%). The commonest reason for admission was decompensated liver disease seen in 32% of patients. 14.5% of patients experienced variceal haemorrhage at or during admission. There was a significant difference in mortality, in-hospital complications and the need for tertiary centre referral between patients with and without cirrhosis. The commonest in-hospital complications were infection and renal dysfunction; 16% of our patients required ICU support. There was no significant difference in median length of stay (LOS) between patients with and without cirrhosis. However patients with cirrhosis had more complex discharge requirements as demonstrated by referral to social services. <h3>Conclusion</h3> Patients with cirrhosis have significantly more complex in hospital stay and discharge needs compared to patients without cirrhosis. Our study has shown a significantly lower mortality for patients with liver disease than previous studies. We suggest that management by a hepatologist and access to tertiary services improves mortality. The complexity of patients with cirrhosis suggests that a multi-professional team is required to reduce overall LOS. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> http://www.bsg.org.uk/images/Commissioning_report/BSG_Commissioning%20Report.pdf
AB0886 Bone Health Assessment of Patients with Juvenile Idiopathic Arthritis: A Comparison between DXA and Bonexpert
Authors: C.M. Nusman, J. Anink, M.A. van Rossum, R.R. van Rijn, M. Maas, L.W. van Suijlekom-Smit
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Chronic inflammatory activity in juvenile idiopathic arthritis (JIA) affects the bone, possibly resulting in growth abnormalities and decreased bone mineral density (BMD). Monitoring the bone status of JIA patients is important for the prevention of fractures and osteoporosis at later age. Dual-energy X-ray absorptiometry (DXA) is most widely used to determine BMD. BoneXpert is a new, feasible and reproducible method for automatic determination of cortical BMD on hand radiographs. Moreover radiation exposure is low and in low-risk peripheral areas. <h3>Objectives</h3> The aim of this study was to compare BoneXpert and DXA in the assessment of BMD in JIA patients. <h3>Methods</h3> Thirty-five JIA patients with available DXA and hand radiograph within a five month time period were included from a tertiary hospital of the Dutch Arthritis and Biologicals in Children register. Outcome measures for BMD were Bone Health Index (BHI) from BoneXpert and BMD total body, BMD lumbar spine and Bone Mineral Apparent Density (BMAD) from DXA. For all outcome measures Z-scores, reflecting the standard deviations compared to a healthy population, were calculated. Correlations between BMD measurements by DXA and BoneXpert were assessed with Pearson correlation coefficients. <h3>Results</h3> The patients in this study had significantly lower mean BMD compared to the healthy population on all BMD measures (p&lt;0.05). The pearson correlation coefficient for the absolute scores was 0.568 (p=0.000) for BMAD vs BHI, 0.665 (p=0.000) for BMD total body vs BHI, and 0.770 (p=0.000) for BMD lumbar spine vs BHI. The correlation between BMAD and BHI is depicted in Fig. 1. The correlation coefficient for the Z-scores of DXA and BoneXpert (0.127-0.322) was not significant. <h3>Conclusions</h3> BHI measured by BoneXpert is correlated to measurements of BMD by DXA. The correlation of Z-scores of BMD measured by the two methods is weaker. Longitudinal studies and assessment of the association of the BMD measurements with outcome (for instance atraumatic fractures) are necessary to further determine the value of BoneXpert in clinical use. <h3>Acknowledgements</h3> The authors wish to acknowledge Hans Henrik Thodberg for his support with and the free use of BoneXpert. <h3>Disclosure of Interest</h3> C. Nusman: None declared, J. Anink Grant/research support: Travel grant Pfizer, M. van Rossum Grant/research support: Travel grant Pfizer, R. van Rijn: None declared, M. Maas: None declared, L. van Suijlekom-Smit Grant/research support: For the submitted work: Dutch Board of health insurances, Pfizer and Abbvie. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2869
SP0159 Transcriptional Programming of Human Macrophages Reveals A Spectrum Model of Macrophage Activation
Authors: J.L. Schultze
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Inflammation is part of many common diseases including autoimmune diseases, infections, but also cancer, obesity or even Alzheimer9s disease. Macrophages are a major cell type involved in inflammation. Transcriptional programming is at the heart of macrophage activation and differentiation. Based on classical approaches we have learned a lot about macrophage activation, polarization, and macrophage function during the last decades, yet our understanding of the complex network of transcriptional programming regulating these processes remains unresolved. We have recently established a large transcriptome dataset of human macrophages stimulated with a diverse set of activation signals. Using a series of bioinformatical approaches, we were able to extend the current M1 versus M2-polarization model to a spectrum model of macrophage activation. In principle, macrophages compute every input signal to a very specific effector program. We are now applying this information to macrophage biology in inflammatory situations to determine novel human macrophage biology. E.g., we have already been able to reveal an unexpected loss of inflammatory signatures in patients with chronic obstructive pulmonary disease. This systematic approach will form the basis for the development of novel diagnostics and therapeutics targeting inflammation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6122
P5-18-06: Taxanes and Cyclophosphamide Are Equally Effective in Breast Cancer: A Meta-Analysis of Ten Phase III Trials in Early and Advanced Disease.
Authors: BE Vriens, DJ Lobbezoo, AC Voogd, J Veeck, VC Tjan-Heijnen
Journal: Cancer Research (2011)

Abstract Background Overall taxanes did not improve survival in metastatic breast cancer trials (n=10 trials), whereas they do so in (neo-)adjuvant breast cancer trials (n=28 trials). We also noticed that in a substantial number of ‘negative’ metastatic trials, taxane-regimens were used without cyclophosphamide. To further explore this, we compared the outcome of studies in early and advanced breast cancer with a similar design, that is all studies substituting taxanes for cyclophosphamide. Methods We identified 10 phase III taxane-based chemotherapy trials in early and advanced disease, in which taxanes were used instead of cyclophosphamide. They all compared a regimen of an anthracycline combined with a taxane versus an anthracycline combined with cyclophosphamide, i.e., AT versus AC. A pooled analysis was performed using the Review Manager software (RevMan 5) provided by the Cochrane Collaboration. Results In total, 5 studies in advanced disease, 2 studies in neoadjuvant, and 3 studies in adjuvant disease setting were included and analyzed for their primary endpoint. In metastatic breast cancer studies, the hazard ratio of overall survival was 1.03 (95% CI 0.92 to 1.15) for taxanes as compared to cyclophosphamide. Also, studies on early breast cancer with a similar design showed no improvement for taxanes, resulting in an odds ratio for pCR of 0.91 (95% CI 0.57 to 1.43) in the neo-adjuvant setting and a hazard ratio for 5-year disease-free survival of 0.96 (95% CI 0.84 to 1.09) in the adjuvant setting. Conclusion Re-assessment of studies of drugs both assessed in metastatic and early breast cancer provides a new tool for improved understanding. This meta-analysis shows that cyclophosphamide in breast cancer patients is equally effective as taxanes, and thus should be considered of pivotal importance in the treatment of metastatic and early breast cancer. Full appreciation of its relevance will prevent replacement of cyclophosphamide in future trials or in daily practice. Funding: Netherlands Organization for Health Research and Development (ZonMw 80–82500-98-10901) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-06.
Abstract 2072: Systematic functional analysis of microRNAs by transfection of 1129 miRNAs into prostate cancer cells
Authors: Paivi Ostling, Suvi-Katri Leivonen, Anna Aakula, Pekka Kohonen, Rami Makela, Merja Perala, Olli Kallioniemi
Journal: Cancer Research (2010)

Abstract The molecular mechanisms behind prostate cancer development, progression and therapy failure are incompletely understood, but the androgen receptor (AR) is almost invariably involved. Altered microRNA (miRNA) expression profiles have recently been demonstrated in a large number of cancer types, including prostate cancer. These short RNA molecules of ∼21 bases regulate mRNA stability and translation by base-pairing mainly to the 3’-untranslated region (3′UTR) of their targets. In this study, we analyzed the functional impact of miRNA transfections on prostate cancer cell growth, survival, and expression of the AR protein. Seven prostate cell lines (LNCaP, LAPC-4, MDA-PCa-2b, 22Rv1, CWR-1R, RWPE-1, and EP156T) were screened with 1129 miRNA mimics (Ambion, Dharmacon). Cell viability was measured with CellTiter-Glo® (CTG, Promega) whereas AR, cell proliferation (Ki67) and apoptosis (cPARP) were detected with specific antibodies using protein lysate microarrays as described in our recent publication on estrogen receptor targeting miRNAs (Leivonen et al., Oncogene 2009). Seventy-one of the miRNAs had anti-proliferative or pro-apoptotic functions when transfected to the prostate cancer cell lines. In addition, 17 of these miRNAs down-regulated the AR protein. Western blots were used to verify knockdown, and the direct functional role of the miRNAs was clarified by 3′UTR assays and by analyses of down-stream consequences of the knockdowns. In summary, we have systematically defined those miRNAs that are critical for prostate cancer growth, survival and the expression of the androgen receptor. This integrated, multi-parametric profiling provides new evidence of the role of miRNAs in prostate cancer as well as novel clues for therapeutic targeting by manipulating key pathways and cell survival mechanisms by miRNA transfections. 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 2072.
Cerebrospinal-Fluid Lactic Dehydrogenase and Its Isoenzymes in Infections of the Central Nervous System
Authors: Harry N. Beaty, Steven Oppenheimer
Journal: New England Journal of Medicine (1968)

Twenty-four of 25 patients with bacterial meningitis and nine of 11 with CNS viral infection had increased LDH activity in the CSF. The mean levels were 112.8 units per milliliter in bacterial, 193 units in pneumococcal and 23 units in meningococcal meningitis, and 22.6 units per milliliter in viral infections. In the CSF of patients with bacterial infection isoenzyme fractions 4 and 5 were preponderant, suggesting that the enzyme was derived from granulocytes, because normal CSF, serum and brain tissue have an isoenzyme pattern characterized by a predominance of LDH 1 and 2. In viral infections of the CNS, the mild elevations in LDH were due to fractions 1 and 2, but not 4 and 5. In contrast, patients who died with either bacterial or viral CNS infection had levels of LDH 1 and 2 over 50 units per milliliter, suggesting extensive CNS damage.
Abstract 3459: Loss of <i>p16INK4a</i> gene renders mice more susceptible to DMBA-induced mammary carcinogenesis
Authors: Mohammed Naseemuddin, Tahseen H. Nasti, Nabiha Yusuf
Journal: Cancer Research (2010)

Abstract Breast cancer is the most common type of cancer diagnosed in women. The incidence of breast cancer varies with environmental influences, including carcinogen exposure. Polyaromatic hydrocarbons (PAH), have been implicated as etiologic agents in breast cancer. Exposure occurs primarily through the smoking of tobacco, inhalation of polluted air, and ingestion of charred foods. One such example of a carcinogenic polyaromatic hydrocarbon is 7,12-dimethylbenz(a)anthracene (DMBA) which in animal models, induces mammary adenocarcinoma. p16, a low molecular weight tumor suppressor protein, and a major CDK inhibitor, is the product of a tumor suppressor p16/INK4a gene. It is frequently inactivated in the human tumors. In the present study, we were interested to evaluate the role of p16INK4a in DMBA-induced mammary carcinogenesis. Tumor latency was higher in p16INK4a−/− compared to WT (C3H/HeN) counterparts. Tumors from p16INK4a−/− mice were very aggressive as revealed by PCNA and Ki67 staining and qRT-PCR analysis. The levels of angiogeneic markers CD31 and VEGF were also higher in the tumors of p16INK4a−/− mice as compared to WT mice. These results indicate that restoration of p16INK4a−/− function can be helpful in reducing mammary tumors caused by environmental pollutants like DMBA. 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 3459.
PREVALENCE OF TIBIAL ARTERY AND PEDAL ARCH PATENCY BY ANGIOGRAPHY IN PATIENTS WITH CRITICAL LIMB ISCHEMIA AND NON-COMPRESSIBLE ABI (≥1.4)
Authors: Mandeep Randhawa, Grant Reed, Kevin Grafmiller, Heather Gornik, Mehdi Shishehbor
Journal: Journal of the American College of Cardiology (2016)
Case 40-2003
Authors: Benjamin D. Gold, Sjirk J. Westra, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 14-month-old boy was admitted to the hospital because of recurrent abdominal distention, vomiting, and diarrhea.The boy had been born at another hospital at 34 weeks' gestation and weighed 2.56 kg at birth. He had been admitted to the newborn intensive care unit for three days, during which time he received antibiotics and had an unremarkable course. He was bottle-fed and tube-fed on his first day of life but was breast-fed beginning on the second day.His mother had had ulcerative colitis for 22 years (since the age of 20 years); it was controlled with hydrocortisone . . .