tbuckley/cabot-search huggingface dataset:
Abstract 1380: Mechanisms of resistance to antiangiogenic therapy in preclinical models of head and neck squamous cell carcinoma (HNSCC)
Authors: Rekha Gyanchandani, Jennifer R. Grandis, Seungwon Kim
Journal: Cancer Research (2012)

Abstract Purpose: The Vascular Endothelial Growth Factor (VEGF) is ubiquitously expressed and targeted with FDA-approved agent bevacizumab in many types of cancer including colon, lung and renal carcinoma. In head and neck cancer, bevacizumab is under active clinical investigation. However, its efficacy in most cases is limited, with only modest response rates observed in the clinical trials. These incomplete drug responses suggest the presence of alternative signaling mechanisms that compensate for VEGF blockade. The proinflammatory cytokine, Interleukin 8 (IL-8) is known to promote tumor angiogenesis, and is coexpressed with VEGF in HNSCC. Hence, IL-8 signaling may be a possible mechanism of resistance to anti-VEGF therapy. Experimental Design: In this study, we assessed the efficacy of bevacizumab in preclinical HNSCC models to identify tumors that were sensitive or resistant to the treatment. In order to identify potential mediators of bevacizumab resistance, we evaluated the angiogenic profile of HNSCC cells from the non-isogenic pair of sensitive and resistant cell lines by performing angiogenesis antibody array. We further examined the potential contribution of IL-8 signaling to the in vivo growth of bevacizumab-resistant xenografts, using shRNA-mediated knockdown of the IL-8 gene. Results: HNSCC cell lines showed a range of response to bevacizumab in vivo. Interestingly, the resistant cell lines expressed high levels of proangiogenic factors including IL-8, IL-1a and VEGF compared to the sensitive cell lines. Further, combined inhibition of VEGF and IL-8 in the resistant xenografts resulted in a significant reduction in tumor volume and microvessel density compared to targeting VEGF alone. Conclusions: Our results indicate that HNSCC xenografts display a differential response to anti-VEGF therapy. IL-8 was the most differentially expressed protein in the angiogenic signature of the bevacizumab-resistant and sensitive cells. Finally, abrogation of IL-8 signaling sensitized the resistant xenografts to anti-VEGF therapy. These findings suggest that IL-8 may be associated with anti-VEGF resistance in HNSCC. Hence, co-targeting of VEGF and IL-8 may improve antiangiogenic therapeutic efficacy. 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 1380. doi:1538-7445.AM2012-1380
Abstract 805: mTORC protein levels affect class switch recombination, somatic hypermutation, and antibody production
Authors: Shuling Zhang, Margaret Pruitt, Dena Tran, Wendy DuBois, Richard Robinson, Beverly A. Mock
Journal: Cancer Research (2011)

Abstract Mammalian target of rapamycin (mTOR) regulates cell growth, cell cycle, and survival through two main complexes, mTORC1 and mTORC2. In our previous studies, striking decreases in both size and number of B cells were seen in mice with constitutive reductions in protein levels of both mTOR complexes. In addition, there were alterations in B cell differentiation with partial blocks in B cell development in the bone marrow. In our current studies, we have focused on their defect in antibody production. When challenged with either NP-CGG (T-dependent antigen) or NP-LPS (T-independent antigens), reduced IgG antibody titers to NP antigens were seen in mice with constitutive reductions in mTOR protein levels, despite equivalent levels of total antibody production; high affinity antibody production was also less. The numbers of germinal centers were reduced in the spleens of the mTORC1/2-compromised mice compared to their wild-type littermates. Fewer B cells from the mTORC1/2-compromised mice were able to undergo class switching from IgM to IgG. In addition, germinal center B cells from these mice exhibited reductions in somatic hypermutation rates of their immunoglobulin loci. Studies are currently underway to evaluate the ability of these mice to respond to an in vivo challenge of live bacteria. 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 805. doi:10.1158/1538-7445.AM2011-805
PWE-137 The Bsg Hepatology Dataset: Does It Work In Practice?
Authors: G Sheiybani, D Durrant, K Pritchard, M Bunting, JL Brown, C Hollywood
Journal: Gut (2014)

<h3>Introduction</h3> Clinical diagnosis and procedure coding for hospital admissions is mandatory in order to receive payment through the NHS tariff system. This does not extend into outpatient attendances where, to date, there has not been a nationally agreed process for coding. In order to address this, Connecting for Health (superseded by the Health and Social Care Information Centre), in 2013, invited clinical subspecialty societies to submit codes (limited to approximately 100) that would encapsulate 90% of their outpatient diagnoses. In this study we sought to validate the BSG hepatology subset* to see if it a) met the scope criteria for HSCIC and b) could be clinically useful in outpatient resource planning. <h3>Methods</h3> We have studied the outpatient clinic letters in patients seen by hepatologists or hepatology nurse specialists in the Gloucestershire outpatient departments. A spreadsheet with datafields for postcode, diagnoses and SNOMED mappings within the BSG dataset was developed. Microsoft MapPoint® was used to examine the geographic distribution of the cohort with the intention of improving follow-up arrangements for patients in relation to the location of community hospitals. <h3>Results</h3> From 236 patients studied to date, 100% of patients could be assigned a code from within the dataset. However, 32.2% had alternative/co-existing diagnoses that could also be legitimately coded. In order to be clinically useful the outpatient record should contain datafields for both aetiology (specific) and stage of liver disease (generic). For example, the MapPoint exercise provided an insightful distinction between requirements for a viral hepatitis or cirrhosis clinic in community hospitals. <h3>Conclusion</h3> The BSG hepatology dataset satisfies the scoping requirements of HSCIC but a single diagnostic datafield entry is not immediately useful to clinicians, service providers or commissioners since treatment pathways in terms of aetiology and management pathways in terms of stage need not correlate. <h3>Disclosure of Interest</h3> None Declared.
RACIAL/ETHNIC DIFFERENCES IN ATRIAL FIBRILLATION SYMPTOMS, TREATMENT PATTERNS, AND OUTCOMES: INSIGHTS FROM OUTCOMES REGISTRY FOR BETTER INFORMED TREATMENT FOR ATRIAL FIBRILLATION (ORBIT-AF) REGISTRY
Authors: Harsh Golwala, Larry Jackson, DaJuanicia Simon, Gregg Fonarow, Paul Chang, Bernard Gersh, Alan Go, Elaine Hylek, Peter Kowey, Kenneth Mahaffey, Laine Thomas, Eric Peterson, Jonathan Piccini, Kevin Thomas
Journal: Journal of the American College of Cardiology (2015)
O150 LOSS OF GATA4 IN HEPATIC STELLATE CELLS PROMOTES LIVER FIBROSIS
Authors: A. Rojas, I. Delgado, M. Carrasco, D.A. Cano, J.A. Del Campo, R. Gallego-Durán, M.J. Pareja-Mejía, M. Romero-Gómez, F. Martín, B. Soria
Journal: Journal of Hepatology (2014)
Abstract 1987: Identification and characterization of novel Notch3 interacting proteins in ovarian cancer
Authors: Alexander Stoeck, Xu Chen, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2011)

Abstract Ovarian serous carcinoma (OSC) represents one of the most aggressive neoplastic diseases because most cases present at an advanced stage when therapy is usually ineffective. We have previously reported that Notch3 gene amplification and overexpression occurs frequently in OSC. Activation of Notch3 signaling is essential for the survival of OSC cells with Notch3 overexpression, especially in the presence of chemotherapeutic agents. Notch3 pathway activation has been known to transcriptionally regulate an array of genes, including those involved in stem cell biology and oncogenesis in OSC. The current study aims at identifying the binding proteins of Notch-ICD in OSC cells using recombinant human Notch3-ICD protein and protein interaction arrays. We have identified several novel Notch3-ICD interacting proteins. Among them, we focused on characterizing WW domain containing E3 ubiquitin protein ligase 2 (WWP2), a member of the NEDD4 family of ubiquitin-protein ligases. We found that WWP2 specifically co-immunoprecipitated with Notch3-ICD but not with Notch1-ICD, and ubiquitinated Notch3-ICD, leading to its degradation in lysosomes. Overexpression of WWP2 in OVCAR3 cells reduced Notch3 steady state protein levels, suppressed Notch3 reporter activity, and inhibited cellular proliferation. On the other hand, a dominant negative isoform of WWP2, as well as knockdown WWP2 using shRNAs, prevented ubiqutination of Notch3-ICD, increased Notch3-ICD protein levels, and enhanced Notch3 reporter gene activity. Compared to their normal counterparts, including fallopian tube and ovarian surface epithelial cells, OSC cell lines and tissues had a significantly lower mRNA and protein levels of WWP2 while Notch3 protein expression was inversely correlated with WWP2 expression levels. The above results provide new evidence that WWP2 protein is a key regulator of Notch3-ICD protein expression levels in ovarian cancer cells. WWP2 modulates Notch3 signaling activity by regulating its degradation pathway and downregulation of WWP2 may represent a novel mechanism to activate the Notch3 signaling pathway in cancer. 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 1987. doi:10.1158/1538-7445.AM2011-1987
A Serpiginous Plaque on the Trunk
Authors: Lawrence Feigenbaum, Kiran Motaparthi, Mark Fradin
Journal: JAMA Dermatology (2016)

A man in his 70s presented with a 4.0-cm linear plaque with an 8.0-mm erythematous nodule on one end on his right upper abdomen; the lesion appeared 2 months prior and had been mildly itchy. What is your diagnosis?
Phase I Study of Amatuximab in Patients with Advanced Solid Tumors
Authors: Y. Fujisaka, T. Kurata, K. Tanaka, T. Kudo, K. Okamoto, J. Tsurutani, H. Kaneda, C. Kitamura, M. Namiki, K. Nakagawa
Journal: Annals of Oncology (2013)
OC-070 Perceived Delay among Patients with Colorectal, Stomach and Oesophageal Cancer: Analysis of Data from a National GP Audit
Authors: C Dobson, G Rubin
Journal: Gut (2013)

<h3>Introduction</h3> The UK has significantly poorer cancer survival rates than comparable countries and diagnostic delay is perceived to be a significant contributory factor to this. The RCGP National Audit of Cancer Diagnosis in Primary Care (2009/10) included data on 3655 patients with colorectal and gastro-oesophageal cancer, including free text comments on avoidable delays in diagnosis, as perceived by the participating GPs. The aim of this study was to identify the principal causes of delay, as perceived by GPs, and how they differ by cancer site. <h3>Methods</h3> Avoidable delay was reported for 36% of patients with colorectal cancer, 37% gastric cancer and 35% oesophageal cancer. Free text reports of the nature of the delay were available for 753 (28%) colorectal, 87 (28%) gastric and 164 (27%) oesophageal cancer patients. An extended version of The Model of Pathways to Treatment (Walter <i>et al</i> 2011) was developed for use as the analytical framework. Comments were categorised by CD with uncertain cases discussed and resolved with GR. In order to validate GP perceptions of diagnostic delay we compared categorised primary care and referral intervals for patients with and without perceived delay. <h3>Results</h3> Primary care and referral intervals were significantly longer for patients with a perceived avoidable diagnostic delay (p = &lt;0.0001), for all three cancer sites. The commonest reasons for delay for colorectal, gastric and oesophageal cancer patients were GP appraisal (29%, 14%, 16% respectively), referral delays (e.g. routine rather than 2 week wait) (13%, 23%, 32% respectively) and investigation delays (28%, 34%, 27% respectively). For colorectal cancer patients, help seeking delay was also a significant cause of delay (8%). Because causes of delay were reported by GPs there was a potential reporting bias, with delays occurring prior to first consultation or in secondary care possibly being under-reported. <h3>Conclusion</h3> Diagnostic delay for patients with upper and lower GI cancers is multi-faceted, with GP appraisal and type of referral perceived as substantial contributors. Interventions aimed at reducing the time to diagnosis should be targeted at the key causes and settings of delay for different cancer sites. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Walter, F. Webster, A., Scott, S. &amp; Emery, J. (2012) ‘The Andersen Model of total patient delay: A systematic review of its application in cancer diagnosis.’ Journal of Health Services Research and Policy Vol.17, No.2, pp.110–118.
Sense in Antisense Therapy for Spinal Muscular Atrophy
Authors: Alex MacKenzie
Journal: New England Journal of Medicine (2012)

A signal feature of spinal muscular atrophy (SMA) is the dying back of motor neurons. This is caused by a loss-of-function mutation in SMN1. Administration of an oligonucleotide that modifies the processing of SMN2, a homologous gene, extends the life span in a mouse model of SMA.
DRUG COATED BALLOON ANGIOPLASTY FOR INFRA-INGUINAL PERIPHERAL ARTERIAL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Bhalaghuru Chokkalingam Mani, Moses Mathur, Riyaz Bashir, Jeffrey Goldstein, Gregory Mishkel, Nilesh Goswami, Ehrin Armstrong, Vikas Aggarwal
Journal: Journal of the American College of Cardiology (2016)
Abstract 4938: Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor.
Authors: Cheuk-Lun Lee, Philip CN Chiu, Laura Hautala, William SB Yeung, Ulf-Håkan Stenman, Hannu Koistinen
Journal: Cancer Research (2013)

Abstract Human chorionic gonadotropin (hCG) is a heterodimer consisting of an α- and a β-subunit (hCGα and hCGβ) that are non-covalently linked. Intact hCG, but not free subunits, bind to the LH/hCG receptor. Expression of hCG and hCGβ has been observed in several cancers. Most trophoblastic tumors of placental and germ cell origin produce hCG, while many non-trophoblastic tumors, including bladder, renal and gastrointestinal cancers, often produce hCGβ, and increased serum concentrations of these are associated with adverse prognosis. hCG has been found to stimulate trophoblast invasion. The stimulatory activity has especially been ascribed to a hyperglycosylated form of hCG (hCG-h) expressed in early pregnancy. hCG-h is also a major form of hCG produced by choriocarcinoma and by testicular cancers, although tumor-derived hCG-h is often glycosylated differently than that produced by the placenta. We aimed to compare different forms of hCG in their stimulatory activities on the invasion of JEG-3 choriocarcinoma cells. Various forms of hCG and hCGβ were purified from urine of one patient with nonseminomatous testicular cancer, one with invasive molar disease, and pregnant women. Both hCG and hCGβ, and their hyperglycosylated forms stimulated the invasion of JEG-3 cells. However, cancer-derived hCG-h was more effective than “regular” hCG in stimulating the invasion. Down-regulation of the LH/hCG receptor by RNA-interference did not significantly reduce the effect of hCGβ and hCG on cell invasion. Increased invasion was associated with increased activity of MMP-2, MMP-9 and uPA in conditioned culture medium from JEG-3 cells. Our findings suggest that hCG and hCGβ stimulates the invasion of choriocarcinoma cells independent of the classical LH/hCG-receptor. Citation Format: Cheuk-Lun Lee, Philip CN Chiu, Laura Hautala, William SB Yeung, Ulf-Håkan Stenman, Hannu Koistinen. Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor. [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 4938. doi:10.1158/1538-7445.AM2013-4938
Growing Pains for the Medicare Hospice Benefit
Authors: David G. Stevenson
Journal: New England Journal of Medicine (2012)

Interview with Dr. David Stevenson on hospice and other end-of-life care in the United States. (15:22)Download Medicare's current approach to hospice permits patients to choose a well-defined end-of-life care benefit, but it has tradeoffs in terms of eligibility, distinctions between curative and palliative therapy, and the segregation of hospice care from other services.
THE ADOLESCENT ATHLETE’S HEART ACCORDING TO 3 INTERNATIONAL CRITERIA: WHICH IS BEST AND FOR WHICH ETHNICITY?
Authors: Aneil Malhotra, Harshil Dhutia, Rajit Khosla, Tee Joo Yeo, Rajay Narain, Mark Cassar, Kyle Conley, Charlotte Brathwaite Shirley, Grant Nolan, Hugo Layard-Horsfall, Keerthi Prakash, Maite Tome, Michael Papadakis, Sanjay Sharma
Journal: Journal of the American College of Cardiology (2016)
Endoscopic sphincterotomy using a pull-type sphincterotome with an attached stabilizer in patients with Billroth II gastrectomy
Authors: K. Fujita, S. Myojo, S. Yoshida, Y. Kawase
Journal: Endoscopy (2011)

Because a conventional sphincterotome is designed for an orientation of 11 – 12 o’clock, it is challenging during endoscopic sphincterotomy (EST) to incise the papilla hood in the ideal position (5 – 6 o’clock) from an inverted position in patients with Billroth II (BII) gastrectomy [1] [2] [3] [4]. After obtaining written informed consent, we attempted EST on seven consecutive patients with bile duct stones, who had previously undergone BII gastrectomy. Patient details are given in [Table 1]; mean age was 74.4 (range 47 – 85 years).
LOW-DOSE CORONARY CTA AT 70 KV: EFFECT OF ITERATIVE RECONSTRUCTION ON IMAGE QUALITY AND CORONARY ATHEROSCLEROTIC PLAQUE DETECTION
Authors: Annika Schuhbaeck, Michaela Hell, Monique Tröbs, Daniel Bittner, Gerd Muschiol, Stephan Achenbach, Michael Lell, Michael Uder, Mohamed Marwan
Journal: Journal of the American College of Cardiology (2015)
LEFT ATRIAL FUNCTION AND OUTCOME OF CATHETER ABLATION IN PATIENTS WITH ATRIAL FIBRILLATION: A MAGNETIC RESONANCE STUDY
Authors: Mohammadali Habibi, Joao Lima, Irfan Khurram, Stefan Zimmerman, Vadim Zipunnikov, David Spragg, Hiroshi Ashikaga, Joseph Marine, Hugh Calkins, Saman Nazarian
Journal: Journal of the American College of Cardiology (2015)
SP0119 The aryl hydrocarbon receptor: An interpreter of the micro-environment
Authors: M. Veldhoen
Journal: Annals of the Rheumatic Diseases (2013)

The transcription factor aryl hydrocarbon receptor (AhR) is selectively expressed in some immune cells, importantly in both Th17 and gamma/delta T cells. Its activation is important for optimal development of the Th17 cell subset and results in enhanced activation of both Th17 and IL-17 producing gamma/delta T cells. Immune protection against invading microorganisms starts at epithelial barrier sites. At these sites reside specialised intra-epithelial lymphocytes (IELs) that are important not only as a first line of defence but also in epithelial barrier organisation and wound repair. Especially at epithelial sites, AhR activation in response to endogenous and exogenous ligands may constitute a way in which environmental stimuli could affect the immune status. New data regarding the role of such stimulation will be discussed. <h3>Disclosure of Interest</h3> None Declared
OUTCOMES AND PROGNOSIS OF PATIENTS WITH KNOWN, NEWLY DIAGNOSED AND WITHOUT DIABETES MELLITUS PRESENTING WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: FROM THE HORIZONS-AMI STUDY
Authors: Konstanze Ertelt, Sorin Brener, Roxana Mehran, Girma Minalu Ayele, Gregg Stone
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-251: Comparison of MicroRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues.
Authors: Wei Meng, Joseph McElroy, Stefano Volinia, Jeff Palatini, Sarah Warner, Leona Ayers, Kamalakannan Palanichamy, Arnab Chakravarti, Tim Lautenschlaeger
Journal: Cancer Research (2013)

Abstract Purpose/Objective(s): MicroRNAs regulate several aspects of tumorigenesis and cancer progression. Most cancer tissues are archived formalin-fixed and paraffin-embedded (FFPE). While microRNAs are a more stable form of RNA thought to withstand FFPE-processing and degradation there is only limited evidence for the latter assumption. We examined whether microRNA profiling can be successfully conducted on FFPE cancer tissues using SOLiD ligation based sequencing. Materials/Methods: Nine paired human malignant tissue samples were received. Remnant surgical tissues were taken after diagnostic samples were secured from patients (five males and four females; median age 58 years, range 39-78 years) with breast invasive ductal carcinoma (2), renal clear cell carcinoma (2), lung squamous cell carcinoma (1) and adenocarcinoma (1), prostate adenocarcinoma (1), metastatic melanoma (1), and sarcoma of thigh (1). RNA from FFPE samples were extracted using Recover All Total Nucleic Acid Isolation Kit (Life Technologies Corporation, Carlsbad, CA). Small RNAs from FFPE and fresh frozen samples were prepared for SOLiD (Version 4) system, and reads data were analyzed by using the SOLiD™ small RNA Analysis pipeline (Life Technologies), then normalized as reads per million (RPM). Results: Tissue storage times (2-9 years) appeared to not affect the number of detected microRNAs in FFPE samples compared to matched frozen samples (paired t-test p&amp;gt;0.7). Correlations of microRNA expression values were very high across microRNAs in a given sample (Pearson's r=0.74-0.94). Higher variance of expression values among samples was associated with higher correlation coefficients between FFPE and frozen tissues. One of the FFPE samples in this study was degraded for unknown reasons with a peak read length of 17 nucleotides compared to 21 in all other samples. The number of detected microRNAs in this sample was within the range of microRNAs detected in all other samples. Conclusion: Ligation-based microRNA deep sequencing on FFPE cancer tissues is feasible and RNA degradation to the degree observed in our study appears to not affect the number of microRNAs that can be quantified. Citation Format: Wei Meng, Joseph McElroy, Stefano Volinia, Jeff Palatini, Sarah Warner, Leona Ayers, Kamalakannan Palanichamy, Arnab Chakravarti, Tim Lautenschlaeger. Comparison of MicroRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues. [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 LB-251. doi:10.1158/1538-7445.AM2013-LB-251