tbuckley/cabot-search huggingface dataset:
Abstract 3874: An isogenic cell line approach to MMTV integration site analysis
Authors: Janice E. Knepper, Lauren Acosta, Justin Saunders, Chong-Wai Tio, Tianjiao Wang, Keith G. Danielson
Journal: Cancer Research (2011)

Abstract Development of mammary tumors in mice carrying the retrovirus, mouse mammary tumor virus (MMTV), occurs by insertional mutagenesis in which viral transcriptional regulatory elements drive increased expression of adjacent genes. Several oncogenes have been identified due to their ability to cause loss of cell growth control in this system. However, most virus positive tumors feature multiple integration sites, and determination of which may be significant in tumor growth represents a challenge to validation of importance of integration site genes. We have developed a panel of more than 20 independent cell lines derived from MMTV-induced tumors of BALB/c mice. Analysis of common integration sites led to the identification of Tmem170, encoding a predicted transmembrane protein of 144 amino acids. Tmem170 RNA is highly expressed in several cell lines in the panel, but not in normal mouse mammary gland. Rabbit antiserum against a peptide in the predicted extracellular domain revealed a single band migrating at approximately 40 KDa in SDS gels. We developed a panel of vectors encoding silencing RNAs targeting Tmem170 and introduced these into cell lines expressing the Tmem170 RNA. Two independent cell lines exhibited decreased doubling times in culture when Tmem expression was silenced. The cells were introduced into the mammary fat pads of isogenic BALB/c mice and silenced lines exhibited dramatically decreased tumor growth. These studies support Tmem170's oncogenic role in tumor growth. In addition, the use of an easily manipulated cell line model for assessing the contribution of upregulated genes to tumorigenesis in immune competent animals allows for testing of other potential oncogenes. 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 3874. doi:10.1158/1538-7445.AM2011-3874
Abstract 2106: Regulation of Rb1 and caspase 3/7 by miR-17-5p, miR-132/-212, and miR-337-3p: Oncogenic role of miRNAs in pancreatic cancer
Authors: Jong Kook Park, Jinmai Jiang, Yuriy Gusev, Megan R. Lerner, Daniel J. Brackett, Thomas D. Schmittgen
Journal: Cancer Research (2010)

Abstract Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal forms of cancer. Reasons for the high mortality associated with this disease include a lack of effective treatments and poor early detection methods. Enhanced understanding of the pathways that are deregulated in PDAC could lead to improved therapies and diagnostics. We and others have reported a microRNA expression signature that is associated with PDAC. The purpose of this study was to identify target genes and pathways that are regulated by miRNAs with altered expression in PDAC. We found several miRNAs including miR-17-5p, −132/-212, and −337-3p that have increased expression in clinical specimens of PDAC compared to normal and adjacent benign pancreas. miR-132 and −212 are located within 472 bp of each other on chromosome 17, have the identical seed sequence and should therefore regulate the identical targets. Through a luciferase reporter assay and western blotting, we found that miR-132/-212 directly regulate the expression of the tumor suppressor Rb1 in the pancreatic tumor cell lines HS766T and PANC-1. Over expression of these miRNAs (miR-132/-212) either through stable expression or pre-miR oligos increased the proliferation rate of HS766T and PANC-1 cells. Expression of 18 genes that are transcriptionally regulated by the E2F including Cyclin A, Cyclin B, PCNA, MCM2, MKI67 and others was increased following miR-132/-212 over expression. Additional genes that are predicted to be targeted by these miRNAs include procaspase 3 (miR-337-3P) and procaspase 7 (miR-132/-212 and miR-17-5p). These caspases are essential in executing programmed cell death in tumors. Western blotting and luciferase reporter assays determined that procaspase 3 and procaspase 7 are regulated by miR-337-3P and miR-132/-212 &amp; miR-17-5p, respectively. Our data strongly suggest that over expression of miR-132/-212 contributes to the enhanced proliferation that is observed in pancreatic cancer. Furthermore, this study is the first to discover that main effector caspases, caspase 3 and 7, are post-transcriptionally regulated by miRNAs. Our findings suggest that resistance to chemotherapeutics in pancreatic tumor tissues may be linked to reduced expression of these procaspases. 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 2106.
The evolution and development of human social systems requires more than parasite-stress avoidance explanation
Authors: Jason Grotuss
Journal: Behavioral and Brain Sciences (2012)

Abstract Fincher &amp; Thornhill (F&amp;T) present a model of in-group assortative sociality resulting from differing levels of parasite-stress in differing geographical locations in the United States and the world. Their model, while compelling, overlooks some important issues, such as mutualistic associations with parasites that are beneficial to humans and how some religious practices increase parasite risk.
Intrathoracic Renal Ectopia Mimicking CSF Leakage on Radionuclide Cisternography Demonstrated by SPECT/CT
Authors: Yu-Li Chiu, Daw-Guey Tsay, Chin Hu, Chia-Shang Wu, Wei-Ning Du, Nan-Jing Peng
Journal: Clinical Nuclear Medicine (2011)

We report a case of 33-year-old man who had clinically suspicious spontaneous intracranial hypotension owing to aggravated headache after sitting and standing. Radionuclide cisternography revealed slightly asymmetric uptake at bilateral paraspinal regions of upper T spine, and a focal area of increased uptake at left paraspinal region of lower T spine. The site of CSF leakage was initially taken for the latter. However, SPECT/CT identified CSF leakage at upper T spine and a left intrathoracic renal ectopia.
SP0017 How Does Anatomy Help to Learn Ultrasound?
Authors: I. Moller
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Gross anatomic study is clearly fundamental in the understanding of the ultrasound image and the term "sonoanatomy" has been applied to this convergence. "Sonoanatomy"also implies a different and dynamic way of exploring the superficial musculoskeletal and neurovascular structures and their relationships. The popularity of "sonoanatomy" courses among musculoskeletal practitioners of ultrasound is evidence of their desire to enhance their level of professional excellence in this area. In the very near future, ultrasound will become, not only an important educational component in the formation of medical practitioners, but will find important applications in the study of human anatomy itself. These programs are already receiving attention in a number of institutions. <h3>Disclosure of Interest</h3> None Declared
From Palliation to Targeted Therapy in Myelofibrosis
Authors: Alessandro M. Vannucchi
Journal: New England Journal of Medicine (2010)

Myelofibrosis is a very debilitating chronic myeloproliferative neoplasm.1 It may be primary or develop late in the course of essential thrombocythemia or polycythemia vera, the two most common and benign myeloproliferative neoplasms. Patients with myelofibrosis have shortened survival and a reduced quality of life. The current treatment is palliative and aimed at alleviating symptoms due to splenomegaly, controlling myeloproliferation, and improving anemia and other cytopenias.In this issue of the Journal, Verstovsek et al. report on the results of a phase 1−2 trial of an oral Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) inhibitor, INCB018424, in advanced myelofibrosis. . . .
Vascular-Bed–Specific Hemostasis and Hypercoagulable States
Authors: Robert D. Rosenberg, William C. Aird
Journal: New England Journal of Medicine (1999)

Hemostasis is a physiologic mechanism that maintains blood in a fluid state within the circulation. The coagulation of blood is mediated by cellular components and soluble plasma proteins. In response to vascular injury, circulating platelets adhere, aggregate, and provide cell-surface phospholipid for the assembly of blood-clotting enzyme complexes. The extrinsic pathway of blood coagulation is initiated when blood is exposed to non-vascular-cell–bound tissue factor in the subendothelial space (Figure 1). Tissue factor binds to activated factor VII, and the resulting enzyme complex activates factors IX and X of the intrinsic and common coagulation pathways, respectively. Factor IX activated by the . . .
AB1123 Bite Force Control in Subjects with Chronic Neck Pain
Authors: M. Testa, T. Geri, S. Roatta, L. Gizzi, F. Petzke, D. Falla
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Even if recent evidences suggest the absence of any relationship between body posture and dental occlusion in provoking spine or temporomandibular disorders,<sup>1</sup> electromyographic studies evidenciated a relationship between temporomandibular disorders and neck pain. Since pain disorders often affect the force production and control because of a feedback impairment, the neck pain might cause a deficit in bite force control. To date no studies were conducted to ascertain such a phenomenon. <h3>Objectives</h3> To investigate the ability to control bite force in subjects with neck pain <h3>Methods</h3> A sample of 13 subjects affected by chronic neck pain and 13 healthy subjects, age and gender matched, were recruited after informed consent. Two flexible force transducers housed in a soft envelope positioned between the first molars teeth constituted the force measuring device. The values of two Maximal Voluntary Contractions (MVCs) were used to generate 4 targets representing percentages (10, 30, 50 and 70%) of the right and left MVCs. The task required was to reach and hold for 5” the force targets randomly displayed on the monitor, by tuning the force exerted on both sides. The subject9s force performance was measured using error indices from the reference target like the Mean Distance (MD) and Offset Error (OE). Between-group differences of the force errors (MD, OE) were analyzed using a wilcoxon rank sum test with alpha set at 0.05. <h3>Results</h3> 13 subjects (10 females, 3 males) with neck pain and a matched control group participated in the study. There were no significant between-group differences in force production for both MD and OE. <h3>Conclusions</h3> The neck pain subjects did not presented any significant difference in bite force control, compared with healty subjects. These results do not support an etiopathogenetic relationship between neck pain and temporomandibular disorders <h3>References</h3> Rocha CP, Croci CS, Caria PH. Is there relationship between temporomandibular disorders and head and cervical posture? A systematic review. J Oral Rehabil. 2013 Nov;40(11):875-81. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6029
Abstract 3982: Cancer genome sequencing analysis, storage, discovery and delivery
Authors: John Z. Sanborn, Charles J. Vaske, Stephen C. Benz
Journal: Cancer Research (2012)

Abstract Genome instability and structural rearrangement is a distinctive hallmark of the cancer genome. With next-gen sequencing technologies, our ability to measure structural rearrangements that occur throughout tumorigenesis and progression has improved significantly, while creating an urgent need for rearrangement discovery, analysis, and visualization methods to aid in our understanding of these events. We have developed a sequencing analysis pipeline that streamlines the discovery of an individual tumor's mutations, small indels, copy number alterations, allele-specific amplifications and deletions, and genomic rearrangements. Rearrangements are refined to base-pair precision using unmapped, putative split reads found in the vicinity of the breakpoint. Results are presented in an interactive, web-based genome browser that provides analysis and visualization of both high-level, processed results as well as the raw data from which they were derived. From the web-based interface, results from multiple samples can be aggregated into user-defined sample cohorts to help identify features that are shared among a significant number of the samples. Using this sequencing analysis pipeline, we discovered high-confident, small- and large-scale somatic events in 17 whole genome glioblastoma multiforme (GBM) tumor samples from The Cancer Genome Atlas (TCGA) project, using their matched normal sequences to filter out germline variants. Among many interesting structural aberrations identified in these samples, we find four samples exhibiting EGFR amplifications and the presence of the EGFRvIII mutant, characterized by the in-frame deletion of exons 2-7 to produce a constitutively active form of the receptor. Comparing the read support of the EGFRvIII-associated breakpoints to the number of normally-mapped reads in the neighborhood suggest that, in all cases, the EGFRvIII mutant emerges after the amplification of wild-type EGFR, existing as a small fraction of total number of EGFR copies. In other samples, evidence of high copy number amplicons containing both MDM2 and EGFR are discovered at detectable levels in the blood sequencing data, raising the possibility that patient-specific PCR-based assays could be developed to quantitate the presence of somatic rearrangements as a proxy to monitor the progression of brain tumors. 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 3982. doi:1538-7445.AM2012-3982
SP0084 Understanding the Importance of Transparency When Using Opportunities to Work with the Pharmaceutical Industry
Authors: A. Bosworth
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Ailsa Bosworth will reflect on the National Rheumatoid Arthritis Society9s experience of working with the pharmaceutical industry over the preceding decade. The presentation will give examples of some collaborative projects the charity has worked on with the pharmaceutical industry, including directly funded and in-kind supported projects, and the accompanying value that has been accrued to the charity and to rheumatoid arthritis patients. The presentation will then go on to consider factors that influence the charity9s decisions to participate in individual project proposals and outline the codes of conduct which NRAS abides by when agreeing to work with industry. Finally, the presentation will consider national policy developments that affect UK health charities and explain how NRAS has begun to respond to these challenges through adopting new measures to further enhance transparency. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6318
Abstract 2257: The survival impact of XPA and XPC genetic polymorphisms on patients with esophageal cancer
Authors: Jang-Ming Lee, Pei-Wen Yang, Ching-Yueh Hsieh, Pey-Yu Tsai, Chun-Hui Chen, Jin-Shing Chen, Pei-Ming Huang, Hsao-Hsun Hsu, Sunn-Wen Kuo, Yung-Chie Lee
Journal: Cancer Research (2011)

Abstract Purpose: To investigate the association of the genetic variants in xeroderma pigmentosum groups A (XPA) and C (XPC) with the overall survival duration of the patients with esophageal cancer. Patients and Methods: A total of 531 patients with a diagnosis of esophageal cancer were enrolled in the study. The genetic variants of XPA in 5’UTR (rs1800975) as well as XPC at exon 15 Lys939Gln (rs2228001) were analyzed with the TaqMan assay from the genomic DNA of peripheral leukocytes. The association of the genotypes and the survival of the patients were analyzed with Cox's multivariate analysis. Results: There was no significant difference of XPA and XPC genotype distribution among patients with various clinical profiles. The overall survival of the patients was significantly influenced by the tumor stage, cell type (squamous cell carcinoma vs. adenocarcinoma) and curative surgical resection (p&amp;lt;0.05 respectively). There was an insignificant unfavorable trend for survival outcome of the patients with XPA 5’UTR (rs1800975) C/T or XPC Lys939Gln (rs2228001) G/G genotypes, compared with those who with other genotypes. Cox's multivariate analysis revealed that accumulation with any one this two unfavorable genotype would associate with a significantly increased risk of death (adjusted HR [95% CI]: 1.27[1.07-1.50]; p=0.005). Compared to those patients without any of these unfavorable genotype, simultaneously having both of these genotype would impose a significantly higher risk of death on the patients after treatment (adjusted HR [95% CI]: 1.86[1.24-2.81]; p=0.003). Conclusion: Our study demonstrates that the hereditary genetic variants in XPA and XPC may play a role for the clinical outcome of the patients with esophageal 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 2257. doi:10.1158/1538-7445.AM2011-2257
Preliminary Results of Tc-99m ECD SPECT To Evaluate Cerebral Collateral Circulation During Balloon Test Occlusion
Authors: YUKA YAMAMOTO, YOSHIHIRO NISHIYAMA, YOSHIHIRO TOYAMA, KATASHI SATOH, KEIKO IRIE, MOTOOMI OHKAWA
Journal: Clinical Nuclear Medicine (2002)

Purpose The authors obtained noninvasive quantitative measurements of regional cerebral blood flow using Tc-99m L,L-ethyl cysteinate dimer (Tc-99m ECD) SPECT to evaluate cerebral collateral circulation during balloon test occlusion (BTO) of the internal carotid artery and vertebral artery (VA). Methods Five cases associated with an aneurysm and a brain tumor were investigated. After 10 minutes of BTO, a bolus of Tc-99m ECD was injected intravenously and radionuclide angiography was performed. The balloon remained inflated for an additional 5 minutes. After radionuclide angiography was completed, brain SPECT imaging was performed. For quantitative analysis, regions of interest were defined on the transverse images on each side of the anterior cerebral artery and middle cerebral artery territories in cases of occlusion of the internal carotid artery. Regions of interest were defined for the posterior cerebral artery territory and cerebellum in cases of occlusion of the VA. The percentage activity change during BTO was calculated. Results In two of the three patients in whom BTO of the internal carotid artery was performed, the percentage activity reduction of more than 30% was noted in the anterior cerebral and middle cerebral artery territories. These two patients underwent bypass grafting before carotid occlusion. In one of the two patients in whom BTO of the VA was performed, the percentage activity reduction of 16% was noted in the posterior cerebral artery territory. This patient underwent bypass grafting before occlusion of the VA. Conclusion This noninvasive and quantitative method of cerebral blood flow measurement using Tc-99m ECD during BTO appears to have the potential to help select patients who may tolerate temporary or permanent arterial occlusion.
OP0284 Mtor Plays A Decisive Role in the Rheumatoid Mesenchymal Tissue Response to Inflammation
Authors: T. Karonitsch, K. Dalwigk, J. Holinka, F. Sevelda, B. Niederreiter, C. Steiner, M. Bilban, R. Windhager, G. Steiner, J. Smolen, H. Kiener, G. Superti-Furga
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> By integrating microenvironmental cues, mTOR has evolved as a critical determinant for the maintenance of cellular homeostasis and function. As such, the unfolding biology of mTOR revealed a crucial role in cancer, metabolic diseases and ageing. Now, accumulating evidence suggests that mTOR may also have an important modulatory function in the cellular response to inflammatory cues, such as TNF. Whether or not this also applies to fibroblast-like synoviocytes (FLS), particularly in the context of rheumatoid synovitis, remains elusive. <h3>Objectives</h3> To evaluate the role of mTOR in the rheumatoid synovial tissue response to inflammation (TNF). <h3>Methods</h3> A simplified 3-D model of the synovium was used to evaluate the significance of mTOR activity for the inflammatory mesencyhmal tissue response. FLS viability and proliferation was assessed by Annexin/7-AAD staining and a 3H-Thymidine incooperation assay, respectively. mTOR activity was blocked by Torin-1, which is a well known specific inhibitor of mTOR functions. In addition, RA-FLS (n=5) were exposed to TNF (6 hours) in the presence or absence of Torin-1 and the GeneChip® PrimeView array™ was used for gene expression profiling. Assessment of regulated genes was determined via SAM analysis. The expression of selected candidates was validated by Q-PCR and ELISA. To assess mTOR activity in RA-FLS, immunoblotting (IB) was performed using phosphospecific antibodies to TSC2, mTOR, AKT and S6K. <h3>Results</h3> Stimulation of the 3D synovial organ cultures with TNF resulted in hyperplasia of the lining layer at the surface of the spheres. Strikingly, the mTOR inhibitor Torin-1 prevented TNF-induced FLS proliferation and lining layer hyperplasia. Importantly, Torin-1 alone or in combination with TNF did not affect RA-FLS viability. On the other side, gene expression profiling revealed that inhibition of mTOR results in the enhanced production of NFkB regulated (proinflammatory) genes, such as IL-6, IL8, or MMP1. Finally, immunoblotting of FLS lysates demonstrated that the mTOR pathway is activated by TNF, suggesting that the FLS response to inflammation (e.g. TNF) is controlled by a signalling cascade that involves mTOR. <h3>Conclusions</h3> These studies provide insight into determinants of the synovial tissue response to inflammation and suggest a multifaceted regulatory role for mTOR in arthritis, especially in rheumatoid arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2843
P839 HANDLING AN ORAL GLUCOSE LOAD AFTER A 4 WEEK ORAL HIGH FRUCTOSE CHALLENGE AND ITS IMPACT ON FETUIN-A
Authors: C. Kienbacher, D. Lorant, S. Traussnigg, H. Haslacher, P. Steindl-Munda, M. Krebs, G.H. Schernthaner, M. Trauner
Journal: Journal of Hepatology (2014)
The Care of the Terminally Ill: Morality and Economics
Authors: Ronald Bayer, Daniel Callahan, John Fletcher, Thomas Hodgson, Bruce Jennings, David Monsees, Steven Sieverts, Robert Veatch
Journal: New England Journal of Medicine (1983)

Abstract Are current expenditures on dying patients disproportionate, unreasonable, or unjust? Although a review of empirical data reveals that care for the terminally ill is very costly, it is not appropriate to conclude that such expenditures represent a morally troubling misallocation of societal resources. Moreover, though efforts to reduce the costs of caring for the dying are not unreasonable, they must be undertaken with great caution. At present, such efforts should concentrate on three basic goals: development of better criteria for admission to intensive- and critical-care units; promotion of patient and family autonomy with regard to decisions to stop or refuse certain kinds of treatment; and promotion of alternative forms of institutional care, such as hospice care. The most difficult moral problems will arise when patients and their physicians seek access to therapies judged only marginally useful. There may be conflict between administrators with broad institutional responsibilities and clinicians committed to particular patients. (N Engl J Med 1983; 309:1490–4.)