tbuckley/cabot-search huggingface dataset:
Abstract 2062: HIF-1 is required for ErbB2-mediated anoikis resistance
Authors: Kelly A. Whelan
Journal: Cancer Research (2011)

Abstract We have previously established hypoxia as an inhibitor of anoikis in mammary epithelial cells as exposure to hypoxic conditions results in suppression of anoikis and delays lumen formation in 3D acinar structures. Inhibition of anoikis in this system is dependent upon both maintenance of EGFR-mediated MAPK signaling and the hypoxia-inducible transcription factor HIF-1. In an effort to determine the mechanism through which hypoxic exposure maintains MAPK signaling in MCF-10As, we compared the gene expression profiles of normoxic and hypoxic 3D acinar structures using microarray analysis. Interestingly, of the more than 70 genes found to be significantly upregulated under hypoxic conditions, a subset of genes emerged that have been implicated in oncogenesis as mediated by, a well-established regulator of anoikis resistance in breast cancer cells. Based on this intersection between HIF and ErbB2 in anoikis-associated signaling as well as the fact that oncogenes, including ErbB2, are known to stabilize HIF under normoxic conditions, we sought to determine what role, if any, HIF-1 plays in ErbB2-mediated oncogenesis. MCF-10A cells overexpressing ErbB2 indeed show increased levels of HIF-1α mRNA and protein under normoxic conditions. We show, for the first time, that depletion of HIF-1 from ErbB2-expressing cells using RNAi leads to restoration of anoikis sensitivity which is associated with both decreased Akt and Erk signaling and the induction of the pro-anoikis protein Bim. This effect was specific to anoikis as depletion of HIF-1 had no effect on survival of attached cells. Similar effects of HIF-1 depletion on anoikis resistance were seen in the human breast cancer cell line SK-BR-3 in which ErbB2 is amplified. Further, expression of at least four genes (integrin alpha 5, angiopoeitin-like 4, endothelin 2 and lysyl oxidase) identified in our microarray analysis as being upregulated by hypoxia also show enhanced expression in normoxic ErbB2-overexpressing cells as compared to parental MCF-10A cells. Here, we suggest that HIF-1 stabilization by ErbB2 under normoxic conditions is novel mechanism through which oncogenes protect cells from anoikis and plan to further explore the mechanism through which HIF-1 augments anoikis resistance in ErbB2-overexpressing cells, possibly by regulating metabolic activity. In addition, we predict that genes whose expression is upregulated by both ErbB2 and HIF-1 may serve as potential new therapeutic targets in the treatment of both hypoxic and ErbB2-positive cancers. 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 2062. doi:10.1158/1538-7445.AM2011-2062
Treatment of Episodic Hyperammonemia in Children with Inborn Errors of Urea Synthesis
Authors: Saul W. Brusilow, Mark Danney, Lewis J. Waber, Mark Batshaw, Barbara Burton, Lynn Levitsky, Karl Roth, Carla McKeethren, Jewell Ward
Journal: New England Journal of Medicine (1984)

Although normal plasma ammonium levels can be maintained in children with inborn errors of ureagenesis, these children are vulnerable to episodic hyperammonemia often resulting in coma and death. To treat such episodes, we designed a therapeutic protocol that included prompt recognition of hyperammonemia, therapy with intravenous sodium benzoate, sodium phenylacetate, and arginine, and nitrogen-free intravenous alimentation. Dialysis was performed if the hyperammonemia was unresponsive to drug therapy. Twelve episodes of hyperammonemia in seven children deficient in carbamyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase were treated; one patient died and the others recovered. In two patients measurement of the distribution of urinary nitrogen revealed that hippurate nitrogen and phenylacetylglutamine nitrogen together accounted for 60 per cent of "effective" urinary waste nitrogen. Successful therapy of episodic hyperammonemia plays an important part in the long-term management of disorders of the urea cycle. (N Engl J Med 1984; 310:1630–4.)
SEPTAL PERFUSION ABNORMALITIES ARE COMMON IN REGADENOSON SPECT MYOCARDIAL PERFUSION IMAGING (MPI) BUT NOT PET MPI IN PATIENTS WITH LEFT BUNDLE BRANCH BLOCK (LBBB)
Authors: Paul Cremer, Richard Brunken, Venu Menon, Manuel Cerqueira, Wael Jaber
Journal: Journal of the American College of Cardiology (2015)
Spontaneous Extravasation from the Ureter Secondary to Aneurysm of the Abdominal Aorta
Authors: Walter A. Schloss, Bernard J. Kaplan
Journal: New England Journal of Medicine (1953)

RECENTLY the 27th case of spontaneous or nontraumatic extravasation from the ureter was reported. The purpose of the present communication is to present a case secondary to an arteriosclerotic aneurysm of the abdominal aorta. In Orkin's1 comprehensive paper, the 26 cases previously recorded in the world literature were summarized.The effect of such an aneurysm on the upper urinary tract has been described. Linton2 states that the retroperitoneal structures most frequently affected are the ureters. Mistaken urologic diagnoses have included perinephric abscess, renal colic, hydronephrosis, renal tumor and perirenal hemorrhage. Actual urologic disturbances secondary to the aneurysms include hydronephrosis, perirenal . . .
Abstract SY01-01: Harnessing genetic dependencies in cancer therapy
Authors: Alan Ashworth
Journal: Cancer Research (2011)

Abstract Many tumors harbor defects in their ability to maintain genomic integrity. This contributes to the mutational burden and likely fosters pathogenesis. We have been exploring therapeutic strategies to exploit these defects. We have used a synthetic lethal approach to target the defect in DNA repair by homologous recombination in tumors with a BRCA1 or BRCA2 mutation. This strategy using PARP inhibitors is showing considerable promise in the clinic. Here, I will describe the approach as well recent work defining determinants of sensitivity and resistance to PARP inhibitors. The application of the synthetic lethal approach to other cancer types will also be discussed. In addition, we have been using high- and medium-throughput RNAi screens to uncover new therapeutic targets for cancer as well as biomarkers of patients who might respond to specific treatments. In particular I will discuss the integration of genomic, gene expression, and RNAi data to generate functional maps of cancer cell lines. 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 SY01-01. doi:10.1158/1538-7445.AM2011-SY01-01
SAT0076 Comparison of anti-interleukin-6 and anti-interleukin-6 receptor antibodies using in vivo functional systems
Authors: S. Shaw, D. Marshall, H. Neale, K. Kretsos, T. Bourne, A. Lawson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The multi-step assembly of the interleukin-6 (IL-6) signaling complex offers the potential for several therapeutic points of intervention in the treatment of rheumatoid arthritis; for example, targeting the cytokine IL-6, the IL-6 receptor (IL-6R; gp80), or gp130. <h3>Objectives</h3> The objective of this study was to compare affinity-matched anti-murine monoclonal antibodies (mAbs) that target either the IL-6 cytokine or the IL-6 receptor in a range of <i>in vivo</i> assays. <h3>Methods</h3> Affinity-matched anti-murine reagents 54E07 mAb (anti-IL-6) and 440-1 mAb (anti-IL-6R; gp80) were evaluated for their ability to inhibit either murine IL-6 or CFA-induced serum amyloid A (SAA). IL-6 is also known to have a significant role in B-cell function; therefore, these antibodies (Abs) were evaluated for their ability to inhibit dinitrophenyl (DNP)-specific Ab production. Furthermore, these Abs were dosed to steady state and their capacity to inhibit collagen-induced arthritis (CIA) in DBA-1 mice was evaluated. <h3>Results</h3> 54E07 mAb produced a ≥90% reduction in the SAA response to both IL-6 and CFA at a dose of 0.1 mg/kg (<i>p</i>&lt;0.01 and <i>p</i>&lt;0.001, respectively). In contrast, doses of at least 1 mg/kg and 3 mg/kg of 440-1 mAb were required to significantly reduce the SAA response (<i>p</i>&lt;0.001 for both doses). <i>In vivo</i> inhibition of IL-6 by 54E07 mAb significantly reduced the DNP-specific IgG response by 72% at doses as low as 0.3 mg/kg s.c. (<i>p</i>&lt;0.05), whereas 440-1 mAb only achieved a significant reduction (80%) in DNP-specific Ab titer at a dose of 10 mg/kg s.c. (<i>p</i>&lt;0.05). In the murine CIA model, both 54E07 mAb and 440-1 mAb achieved a similar reduction (≥97%) in the clinical arthritis score at the same high dose exposure; however, at the same low dose exposure, only 54E07 mAb caused a significant reduction (67%) in clinical score versus controls. <h3>Conclusions</h3> These murine <i>in vivo</i> studies strongly suggest that targeting IL-6 cytokine rather than the IL-6 receptor is the more efficient therapeutic approach for the treatment of autoimmune diseases such as rheumatoid arthritis. <h3>Disclosure of Interest</h3> None Declared
Microarray gene expression studies to discover novel determinants of sensitivity to gefitinib in squamous cell carcinoma of the head and neck
Authors: Susanne Rogers, Robert te Poele, Carol Box, Peter Rhys Evans, Paul Workman, Kevin Harrington, Suzanne Eccles
Journal: Cancer Research (2008)

4849   EGFR is a compelling molecular target in squamous cell carcinoma of the head and neck (SCCHN). EGFR overexpression correlates with aggressive disease and poor patient survival. EGFR inhibition can improve survival in conjunction with radiotherapy, but as a minority of patients respond to single agent EGFR inhibitors, predictive markers of response are keenly sought. We performed genome-wide expression cDNA microarrays to discover novel determinants of sensitivity to gefitinib, an EGFR tyrosine kinase inhibitor (TKI).  3 sensitive (GI 50  50 >10.9 μM) were selected from a panel of 18 cell lines previously characterised by a sulphorhodamine B cell proliferation assay .  RNA from  at least 3 biological repeats of each cell line was hybridised to 30K cDNA arrays (Cancer Research UK DNA microarray facility). Image processing was performed using GenePix Pro 6.0 (Molecular Devices) and files were analysed using Genespring (Agilent Technologies). Ingenuity Pathway Analysis (Ingenuity® systems) software was used to derive pathway information.  1038 genes were differentially expressed between the sensitive and resistant cell lines (Welch t-test; FDR 5%). This data confirmed our previous findings at the protein level that contrast with the published literature: E-cadherin expression is not differentially expressed between gefitinib-sensitive and -resistant SCCHN cell lines, and MET and amphiregulin expression are greater in sensitive than resistant cell lines. 18 genes of interest (p 4  and its substrate laminin 5, and demonstrated increased cell adhesion in gefitinib-sensitive cell lines. The expression of both integrin β 4  and P-cadherin are predictive of sensitivity in previously uncharacterised SCCHN cell lines. These markers may be of value in achieving our aim of identifying predictive markers of response to EGFR TKIs and, ultimately, personalising cancer therapy.
PWE-061 Ercp Practice in a UK District Hospital– are we Meeting the Standards?
Authors: M Kumar, C Ruscanu, D Hanumantharaya, W Melia, R Ede
Journal: Gut (2013)

<h3>Introduction</h3> The 2004 NCEPOD report “Scoping our Practice”<sup>1</sup> had been highly critical of certain aspects of ERCP practise in UK, raising specific concerns about case selection and sedation practise. We analysed our own ERCP practise in a medium sized district hospital with a moderate case workload and a growing proportion of elderly population. <h3>Methods</h3> Retrospective data was collected from 263 ERCPs performed between 2009–2011. Comprehensive information regarding demographics, indications, success and complication rates was recorded from ERCP reports and case notes and our practise was compared to NCEPOD recommendations. <h3>Results</h3> 263 (n) ERCPs were included in this study. Median age was 72 (range = 16–98), 63% were females. 55% of patients were ASA grade 3–4. 84% of ERCPs were of grade 1 difficulty. All ERCP referrals were reviewed and authorised by a consultant gastroenterologist. Indications for ERCP were choledocholithiasis (63%), pancreatic or biliary malignancy with obstructive jaundice (18%), stent removal/replacement (10%), dilatation of biliary ducts with abnormal liver function tests (10%) and others (4%). &gt; 90% of ERCPs were performed with a therapeutic intent and success was achieved in 86% of ERCPs at first attempt. Our successful cannulation rate was of 92%. Only 9.1% of cases were referred to tertiary centres for further management. Prophylactic oral ciprofloxacin was used in 60% of patients. Patients received a combination of midazolam and pethidine with a mean dose (±SD) of 3.2 mg (± 2.03) and 44.3 mg (±16.05) respectively. Reversal with flumazenil or naloxone was not required in any of the patients included in this study. Biliary sphincterotomy was performed in 60%(156), pre-cut sphincterotomy in 2.6%(7), stricture dilatation in 9.5%(25), biliary stenting 30.4%(80), balloon sphincteroplasty 3%(8), balloon trawl 67%(177) and mechanical lithotripsy 8.7%(23). 78.7% of malignant strictures were successfully stented (37). Overall complication rate was 5.7% - moderate haemorrhage requiring blood transfusion in 1.5%(4), post ERCP pancreatitis in 2%(6), sepsis 1.9%(5), duodenal perforation 0.7%(1) and respiratory arrest in 0.7%(1). 30 day mortality rate was 0.76%(2). <h3>Conclusion</h3> In contrast to NCEPOD report, our audit demonstrates that ERCP practise is effective, safe and of high quality in a district general hospital setting. Complication and mortality rates are minimal and comparable to national standards, even in the elderly population. Post ERCP very low sepsis rate is most likely due to use of prophylactic antibiotics (Ciprofloxacin). <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> NCEPOD. Scoping our practise; the 2004 report of the National Confidential Enquiry into patient Outcome and Death. London. NCEPOD 2004. Available from: URL: http://www. ncepod.org.uk/2004.htm
Failure of Zidovudine Prophylaxis after Accidental Exposure to HIV-1
Authors: Joep M.A. Lange, Charles A.B. Boucher, Carla E.M. Hollar, Ed H.H. Wiltink, Peter Reiss, Eric A. van Royen, Marijke Roos, Sven A. Danner, Jaap Goudsmit
Journal: New England Journal of Medicine (1990)

ON the basis of encouraging data from two studies in animals,1 , 2 the manufacturer of the antiretroviral nucleoside analogue zidovudine (formerly azido--thymidine [AZT]) has initiated a placebo-controlled trial to assess the chemoprophylactic efficacy of zidovudine after occupational or nosocomial exposure to the human immunodeficiency virus type 1 (HIV-1).3 , 4 It is unlikely, however, that this trial will be completed soon, given the relatively low risk of infection through occupational exposure.4 In anticipation of the results of the study, several programs of zidovudine chemoprophylaxis for health care workers who have been occupationally exposed to HIV-1 have been implemented.4 The aftermath of a tragic . . .
Incidental Detection of a Single Brain Metastasis from Breast Carcinoma During Tc-99m MIBI Scintimammography
Authors: SANJAY GAMBHIR, RAVINDER SINGH SETHI, SATYAWATI DESWAL
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India Received for publication February 7, 2000. Revision accepted January 26, 2001. Reprint requests: Dr. Sanjay Gambhir, Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India. E-mail: [email protected]
Abstract 79: Emergency Medical Services Utilization in ST-Elevation Myocardial Infarction: Significant Urban Versus Rural Differences
Authors: Katie M Menssen, Timothy D Henry, Barbara T Unger, Jeanne M Oelfke, Christopher E Kapsner, Jeffrey Meland, Joan Krikava, David M Larson
Journal: Circulation (2007)

Background: National practice guidelines and strategies for reperfusion recommend pre-hospital ambulance triage of STEMI patients en route to PCI hospitals. Unfortunately, Emergency Medical Service...
Scientific Sleuths Are a Natural for Cancer Research
Authors: T. Parkins
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Scientific Sleuths Are a Natural for Cancer Research Get access Troy Parkins Troy Parkins Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 11, 1 June 1994, Pages 824–826, https://doi.org/10.1093/jnci/86.11.824 Published: 01 June 1994
Endoscopic Ultrasound-Guided Transmural Internal Drainage of Pancreatic Pseudocyst and Pancreatic Abscess
Authors: Chu Yin-Yi, Lin Cheng-Hui, Ng Soh-Ching, Sung Kai-Feng, Lien Jau-Min, Liu Nan-Jen, Chiu Cheng-Tang
Journal: Endoscopy (2011)

Introduction/Objectives: Traditionally, symptomatic pancreatic pseudocyst is management by surgery, but morbidity and mortality are still high. Endoscopic ultrasound (EUS) with large size working channel can provide minimal invasive transmural endoscopic drainage of pancreatic pseudocyst and abscess.
Commissioners of care for elderly people are "flying blind," says one senior commissioner
Authors: C. White
Journal: BMJ (2011)

<h3>ABSTRACT</h3> Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease centered on progressive death of motor neurons. Despite heritability estimates of 52%, GWAS studies have discovered only seven genome-wide significant hits, which are relevant to &lt;10% of ALS patients. To increase the power of gene discovery, we integrated motor neuron functional genomics with ALS genetics in a hierarchical Bayesian model called RefMap. Comprehensive transcriptomic and epigenetic profiling of iPSC-derived motor neurons enabled RefMap to systematically fine-map genes and pathways associated with ALS. As a significant extension of the known genetic architecture of ALS, we identified a group of 690 candidate ALS genes, which is enriched with previously discovered risk genes. Extensive conservation, transcriptome and network analyses demonstrated the functional significance of these candidate genes in motor neurons and disease progression. In particular, we observed a genetic convergence on the distal axon, which supports the prevailing view of ALS as a distal axonopathy. Of the new ALS genes we discovered, we further characterized <i>KANK1</i> that is enriched with coding and noncoding, common and rare ALS-associated genetic variation. Modelling patient mutations in human neurons reduced <i>KANK1</i> expression and produced neurotoxicity with disruption of the distal axon. RefMap can be applied broadly to increase the discovery power in genetic association studies of human complex traits and diseases.
ONE STEP DERIVATION OF CARDIOMYOCYTES AND MESENCHYMAL STEM CELLS FROM HUMAN PLURIPOTENT STEM CELLS
Authors: Heming Wei, Grace Tan, Manasi Manasi, Pearly Yong, Cai Hong Koh, Ting Huay Ooi, Sze Yun Lim, Philip Wong, Shu Uin Gan, Winston Shim
Journal: Journal of the American College of Cardiology (2012)
Proximal-Type Epithelioid Sarcoma of the Scrotum
Authors: Vien X. Nguyen, Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2012)

Proximal-type epithelioid sarcoma is an uncommon but aggressive soft-tissue malignancy involving proximal body parts especially perineum and genitalia of adult patients. This entity is a variant form of the conventional epithelioid sarcoma, which is frequently encountered at extremities of adolescents or young adults. The authors present a case of proximal-type epithelioid sarcoma of the scrotum with comprehensive staging and monitoring with PET/CT.
Abstract 2652: Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome
Authors: Clelia Madeddu, Mariele Dessi, Filomena Panzone, Roberto Serpe, Giorgia Antoni, Francesco Recchia, Giovanni Mantovani
Journal: Cancer Research (2012)

Abstract Aims: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib +/− megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and six minute walk test. Methods: Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results: The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions: The results of the present study showed a non-inferiority of arm 1 (two drug-combination) vs arm 2 (two drug-combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favourable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS 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 2652. doi:1538-7445.AM2012-2652