tbuckley/cabot-search huggingface dataset:
AI-14 * THE ANTI ANGIOGENIC AND INVASIVE EFFECTS OF AN INTEGRIN INHIBITOR AGAINST BEVACIZUMAB-INDUCED INVASIVE GLIOMA
Authors: J. Ishida, M. Onishi, K. Kurozumi, T. Ichikawa, K. Fujii, Y. Shimazu, T. Oka, Y. Otani, T. Shimizu, I. Date
Journal: Neuro-Oncology (2014)

Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in patients with glioblastoma. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor cell implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. We analyzed the three following groups: untreated, treated with bevacizumab, and treated with a combination of bevacizumab and cilengitide. Next, RNA was extracted from orthotopic U87ΔEGFR brain tumor models. The bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis using the microarray data demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the bevacizumab and cilengitide combination group. This study showed that that the combination of bevacizumab with cilengitide exerted its anti-invasive effect by suppressing the integrin-mediated cell adhesion pathway. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.
SAT0056 Dna methylation analysis identified TBX5 as an important transcription factor in rheumatoid arthritis
Authors: E. Karouzakis, M. Trenkmann, F. Niederer, R.E. Gay, B.A. Michel, D. Kyburz, S. Gay, M. Neidhart
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Changes in DNA methylation and histone marks have been associated with diseases such as cancer, rheumatoid arthritis (RA) and systemic lupus erythematosus. Previously, we performed methylation immunoprecipitation (MeDIP) in combination with human promoter arrays and identified TBX5 as a differentially methylated gene in RA synovial fibroblasts (SF). Now, we want to further examine its role in the pathogenesis of RA and identify specific TBX5 gene targets. <h3>Methods</h3> Synovial tissues from RA and OA patients were stained with antibodies for TBX5, a fibroblast marker specific for collagen prolyl 4 hydroxylases, CD3<sup>+</sup> on T cells, CD68<sup>+</sup> on macrophages and analysed by immunohistochemistry. mRNA and DNA were prepared from synovial tissues, CD3<sup>+</sup> T cells and CD14<sup>+</sup> monocytes of RA patients. Intracellular FACS staining was used to quantify the levels of TBX5 in T cells and monocytes. The expression and DNA methylation status of TBX5 were determined by quantitative SYBR PCR and bisulfite sequencing. Transient transfections with TBX5 expression vector were performed in OASF and RASF. The transfected SF cells were analysed with quantitative SYBR PCR for TBX5 gene targets. <h3>Results</h3> Immunohistochemistry of synovial tissues confirmed that TBX5 is expressed in RA (n=6), but rarely in OA (n=6). The expression of TBX5 was nuclear and mostly localised in the synovial lining of RA tissues. Double labelling of RA tissues with a fibroblast marker showed that the sublining fibroblasts were labelled with TBX5 antibodies. Next, we examined the CD3<sup>+</sup> T cells and CD68<sup>+</sup> macrophages of synovium and found that the CD3<sup>+</sup> T cells and CD68<sup>+</sup> macrophages were expressing variable levels of TBX5. TBX5 transcripts were significantly more expressed in RA than OA tissues (RA dCt: 15.5±0.4 n=10; OA dCt: 18.1±0.9 n=5, p&lt;0.04). The TBX5 promoter was significantly more methylated in OA than in RA tissues as shown by bisulfite sequencing. In addition, CD3<sup>+</sup> T cells and CD14<sup>+</sup> monocytes were expressing significantly higher protein levels of TBX5 than the healthy controls as shown by FACS staining.Transient overexpression of TBX5 in RASF and OASF (n=3 each) showed a 1.5 fold increase of TNFR1 and TNFR2 mRNA as shown recently also in cancer cell lines. <h3>Conclusions</h3> DNA methylation is responsible for the overexpression of TBX5 in RA synovial tissue <i>in vivo</i>. Consequently, TBX5 appears to be a novel regulator of TNFα receptor expression in RA and thereby associated with the chronically activated phenotype of RASF. <h3>Disclosure of Interest</h3> None Declared
Abstract 5092: Localized and disseminated histiocytic sarcoma complex: A canine model
Authors: Nikolaos Dervisis, Shawna L. Klahn, Matti Kiupel, Maciej Parys, Emmalena Gregory-Bryson, Vilma Yuzbasiyan-Gurkan
Journal: Cancer Research (2012)

Abstract Canine histiocytic sarcoma is an aggressive and uniformly-fatal round-cell neoplasm. The localized, peri-articular form of the disease (PAHS) appears to have statistically significant prolonged survival, when compared to the non - peri-articular form of the disease (non-PAHS). Knowledge of the molecular basis for the aggressiveness of the canine histiocytic sarcoma is foundational for developing effective treatments. The aim of this study was to characterize the molecular expression profiles of the different sub-types of the disease. Canine patients, with spontaneously-arising histiocytic sarcoma, were recruited for the study. Tumor tissue samples and peripheral blood were obtained and used for primary cell line development and gene expression analysis. Eight PAHS and 8 non-PAHS tumor samples were selected. RNA extraction, amplification and labeling were performed using standard techniques. Raw gene expression values were obtained using the Affymetrix GeneChip Canine Genome 2.0 Array. Background correction, normalization, PM correction, summarization, and expression analysis were performed using R/affy/limma. Gene set analysis was performed using BRB-ArrayTools, and the Molecular Signatures Database (MSigDB), to investigate gene ontology groups of genes whose expression was differentially regulated. Primary cell lines from tumor biopsies and peripheral blood samples were developed and characterized based on cellular morphology, growth characteristics, and immunophenotyping. In our gene expression array experiments, we identified specific gene transcripts that are more likely to represent true and biologically meaningful differences in expression levels between PAHS and non-PAHS. More specifically, metallopeptidase genes, and homeobox domain gene expression levels were enriched in the PAHS group, while ATP-binding cassette genes, and interleukin 1 receptor signaling gene expression levels were enriched in the non-PAHS group. Our results suggest presence of gene expression signatures that can provide insight in the diverse biologic behavior of the disease and highlight canine spontaneous tumors in understanding tumor biology. 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 5092. doi:1538-7445.AM2012-5092
Müller's Sign
Authors: Suresh Rama Chandran, Rojith Karandode Balakrishnan
Journal: New England Journal of Medicine (2013)

A 43-year-old man with history of rheumatic heart disease presented with a 2-month history of palpitations and breathlessness. On examination, the pulse was regular at 110 beats per minute, and the blood pressure was 180/40 mm Hg. He had a bounding carotid pulse (Corrigan's sign), a collapsing brachial pulse, pistol-shot sounds heard over the femoral arteries (Traube's sign), and a hyperdynamic apex that was shifted laterally and inferiorly. Inspection of the oral cavity showed systolic pulsations of the uvula (Müller's sign; see video). On auscultation, there was a grade 3 early diastolic murmur at the left sternal border and a . . .
AB0638 Systemic lupus erythematosus in east london-ethnic differences
Authors: A. Nandagudi, D. Pyne, T.S. Subhani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SLE is a heterogenous autoimmune disease that is characterised by diverse clinical manifestations and target tissue damage. The prevalence of SLE is estimated to be between 40 and 400 cases per 100,000 individuals (1). African-Americans and Asians are believed to have more severe disease than Caucasians but there are few studies looking at differences in Asian subgroups. <h3>Objectives</h3> To explore the ethnic differances in autoimmune profile and clinical features. <h3>Methods</h3> The SLE clinic at the Royal London Hospital, East London, has a large cohort of Bangladeshi patients. 107 clinical notes from Electronic patient records were reviewed retrospectively to study differences in clinical and autoimmune presentation between this group and other cohorts. <h3>Results</h3> The cohort included 34 blacks, 27 Caucasians, 25 South East Bengali (SEB) and 16 South East non Bengali (SENB). Age range was between 16 to 62 years. Only 4 patients were males. 6 patients were ANA negative. Ds dna was positive in 13% black patients, 18% SEB, 9% Caucasian and 7% SENB patients. Ro was positive in 14% blacks, 7% Caucasians and 8% SEB patients. RNP was positive in 7% black, 2% Caucasians and 10% SE Bengali patients. Fatigue was a feature of 15% black, 9% Caucasians, 7% SEB and 5% SENB patients. Sicca was a feature in 6% blacks, 8% Caucasians, 7% SEB and 5% SENB patients. Arthritis is a feature of 28% blacks, 15% Caucasians, 11% SEB and 7% SENB patients. Arthralgia was a feature of 4% blacks, 9% Caucasians and SEB and 3% SENB patients. Concerning renal profile, 9% black patients had haematuria+proteinuria, 10% exhibited proteinuria and 7% were hypertensive. Among Caucasians 13% had proteinuria, 6% both haematuria and proteinuria and 1% hypertension. Among SEB 13% had proteinuria, 4% both haematuria and proteinuria,and 2% hypertension. Among SENB patients, 7% had haematuria and proteinuria, 6% had proteinuria and 1% hypertension. Renal biopsy among blacks showed focal proliferative glomerulonephritis (FPGN) in 5%, diffuse proliferative glomerulonephritis (DPGN) in 6% and membranous (MGN) in 2%. Among Caucasians 2% showed FPGN and 3% DPGN. Among SEB patients 1% showed DPGN and 4% showed MGN, Among SENB patients 5% showed DPGN, and 2% showed MGN. <h3>Conclusions</h3> The clinical features and autoimmune profile were varied in these 4 ethnic groups.Most SEB patients weredsDNA positive with high incidence of RNP and renal involvement with proteinuria. Genetic as well as environmental and sociocultural factors are likely to contribute to these differences in the incidence and clinical expression. <h3>References</h3> Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. PartI. Arthritis and Rheumatism. 2008;58(1):15–25. <h3>Disclosure of Interest</h3> None Declared
The Esophagogastric Junction
Authors: Ravinder K. Mittal, David H. Balaban
Journal: New England Journal of Medicine (1997)

The lower esophageal sphincter regulates the flow of food between the esophagus and the stomach. It is now clear that both the intrinsic smooth muscle of the distal esophagus and the skeletal muscle of the crural diaphragm constitute the sphincter mechanism at the lower end of the esophagus.1 Furthermore, in normal subjects and patients with reflux esophagitis, transient relaxation of both sphincters rather than diminished lower esophageal sphincter pressure is the major mechanism of gastroesophageal reflux.2 In this article we review the current understanding of the physiology of the sphincter mechanism at the esophagogastric junction and its relation to esophageal . . .
Lung metastasis targeting by a tumor-killing Salmonella typhimurium mutant.
Authors: M. Zhao, H. Ma, L. Zhang, F. Liu, R. M. Hoffman
Journal: Journal of Clinical Oncology (2010)

e13631 Background: We have previously developed a tumor-targeting double auxotroph of Salmonella typhimurium termed A1-R (Cancer Research 66, 7647-7652, 2006; Proc. Natl. Acad. Sci. USA 104, 10170-10174, 2007). A1-R requires arginine and leucine, which disable these bacteria from growing in normal tissue but allow the bacteria to have high antitumor virulence in nude mouse models. In the present study, we have observed the efficacy of A1-R bacteria on Lewis lung cancer-bearing C57 immunocompetent mice. Methods: Lung tumors were obtained after injection of 2×106 Lewis lung cancer cells, expressing red fluorescent protein (RFP), into the tail vein of C57 B16 immunocompetent mice. Three days after tumor cell transplantation, the animals were treated with A1-R bacteria via tail-vein injection. Results: Lung tumor growth was inhibited in the treated group, and the mice had much fewer lung metastases tumors compared to the untreated group. A1-R was also injected into the thoracic cavity of the Lewis lung cancer-bearing C57 mice weekly for three weeks. All animals were sacrificed at the end of the experiment. The excised lungs were weighed and imaged by RFP fluorescence. The lung tumors in the treated group were significantly smaller than in the untreated group. Intrathoracic injection of bacteria allowed 108 bacteria to be administered weekly to the host with no obvious toxicity. Various i.v. doses of A1-R were tested, including bolus treatment with a single i.v. injection, medium dose using weekly i.v. administration, and metronomic treatment using a small dose twice a week, i.v. In contrast to intrathoracic administration of A1-R, bolus treatment was toxic to the host. However, the medium i.v. dose and the i.v. metronomic dosing of A1-R were well tolerated. Conclusions: These results suggest that S. typhimurium A1-R is effective against metastatic tumors in immunocompetent mice which is important for future clinical development of bacterial cancer therapy. No significant financial relationships to disclose.
CHOREA GRAVIDARUM
Authors: Walter C. Weigner
Journal: American Journal of Psychiatry (1937)

Approximately 950 cases of chorea occurring in pregnancy have been studied statistically, to determine what part psychogenic factors may play in its production. Of these, 137 seem to possess evidence of psychogenesis and in these cases, the incidence of previous chorea, rheumatism and cardiac disease is significantly less than in those cases where evidence of psychogenesis is lacking. These findings suggest that chorea gravidarum should not be regarded as an entity, but instead as an expression of a constitutional "anlage" which may be precipitated by various factors. Such factors may be infection, toxicity, or nervous influence originating from acute emotional traumata and psychic conflict relating to pregnancy. A case is reported in which two attacks of chorea are described—the first following an acute infection of the rheumatic type—the second being associated with great conflict relating to pregnancy.
Reply
Authors: Koonlawee Nademanee, Hariharan Raju, Sofia De Noronha, Michael Papadakis, Laurence Robinson, Stephen Rothery, Naomasa Makita, Shinya Kowase, Nakorn Boonmee, Vorapot Vitayakritsirikul, Samrerng Ratanarapee, Sanjay Sharma, Allard C. van der Wal, Michael Christiansen, Hanno L. Tan, Arthur A. Wilde, Akihiko Nogami, Mary N. Sheppard, Gumpanart Veerakul, Elijah R. Behr
Journal: Journal of the American College of Cardiology (2016)
Case 28-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David W. Rattner, Jana C. Sullinger
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 41-year-old woman was admitted to the hospital because of pain in the right lower abdominal quadrant.The patient was well until 36 hours earlier, when she experienced the onset of an insidious, throbbing "ache" in the right lower quadrant of the abdomen, accompanied by anorexia, nausea, and one episode of vomiting of a small amount of bilious liquid without blood. On the following day she consulted a physician, who prescribed bismuth subsalicylate and acetaminophen. The pain became more persistent, awakening the patient from sleep, and remained vaguely localized to the right lower abdominal quadrant. The patient . . .
Abstract 57: Erythropoietin Selectively Preserves Electron Transport Complex IV Activity During Resuscitation from Cardiac Arrest
Authors: Jeejabai Radhakrishnan, Hawnyeu M Moy, Raúl J Gazmuri
Journal: Circulation (2011)

Introduction: We have previously documented in a rat model of VF and closed-chest resuscitation that administration of erythropoietin (EPO) preserves left ventricular distensibility - yielding hemodynamically more effective CPR - and attenuates post-resuscitation myocardial dysfunction. Hypothesis: Given that similar functional myocardial benefits can be elicited by preservation of mitochondrial bioenergetic function, we hypothesized that EPO could mediate the aforementioned myocardial effects in part by preserving activity of electron transport complexes I, III, IV and V (FoF1 ATPase). Methods: VF was electrically induced in 10 Sprague-Dawley male rats and left untreated for 8 minutes before attempting resuscitation by closed-chest resuscitation and delivery of electrical shocks. Rats were randomized to receive 5,000 U/kg of EPO (n=5) or NaCl 0.9% vehicle (n=5) into the right atrium immediately before starting closed-chest resuscitation, with the investigators blind to the assignment. All rats were resuscitated and survived 120 minutes, time at which hearts were removed storing the left ventricles at -80°C. Mitochondria were isolated from frozen tissue and activity of electron transport complexes I, I &amp; III, IV and V measured spectrophotometrically via dichloro indophenol reduction, cytochrome c reduction, cytochrome c oxidation, and phosphate estimation, respectively. Results: Only complex IV activity was significantly higher in EPO compared with NaCl 0.9% treated rats with the levels in EPO rats comparable to the reference levels (Table). Conclusions: EPO ameliorated reductions in complex IV activity prompted by cardiac arrest and resuscitation, an effect that could mediate the favorable myocardial effect of EPO observed during resuscitation from cardiac arrest.
Abstract P5-01-05: Could <i>c-myc</i> amplification replace Cahan's criterias to discriminate secondary from primary angiosarcoma of the breast?
Authors: M Laé, F Hamel, S Hadj-Hamou, B Malfoy, YM Kirova
Journal: Cancer Research (2012)

Abstract Background: Angiosarcomas (AS) are a relatively rare histological subtype of sarcomas. Despite their rarity, AS display remarkable clinical heterogeneity. These tumors can occur in any location in the body, but the breast AS are important part of these tumours. Cahan et al. defined the criteria for the diagnosis of radiation induced sarcomas (RIS), used since 1948: i) prior history of RT; ii) asymptomatic latent period of several years; iii) the occurrence of a sarcoma within a previously irradiated field; iiii) histological confirmation of sarcomatous nature of the post-irradiation lesion. Purpose: The aim of this study is to show a new biological data which can help us to recognize these rare tumors. Material and Methods: Forty-one breast AS were studied (pathological review, clinical and follow-up information obtained), as well as the transcriptome signatures of the radiation tumorigenesis. For all RIS, the patients' radiotherapy plans and hospital records were reviewed and their radiation related nature was confirmed if they respected the classic Cahan's criteria. Interphase FISH was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections from each of the forty-one tumors. Results: Among forty-one breast AS, thirty one were secondary tumors and ten primary tumors. Amplification (5 to 20 fold) of the MYC oncogene was found in all breast secondary AS (31 cases) but in none of the 10 primary AS except one. The relationships between clinical, pathological and biological features are studied. These data point the pathways preferentially involved in the pathogenesis of secondary AS of the breast and may provide the basis for an additional targeted therapy. Conclusion: The presence of c-myc amplification on biopsy or surgical specimen represents an important additional tool to discriminate secondary from primary angiosarcoma of the breast when radiotherapy data are not available. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-05.
SO-01 * PRIMARY INTRADURAL MALIGNANT PERIPHERAL NERVE SHEATH TUMOR: CASE REPORT AND REVIEW
Authors: W. Gump, R. Debski, M. Thompson, J. Elster, A. Spalding, V. Agarwal
Journal: Neuro-Oncology (2014)

Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma which is most commonly encountered in the extremities, and is often associated with neurofibromatosis type 1 (NF-1). Primary intradural lesions are rarely reported, particularly in the pediatric population. A 15 year old girl was referred to neurosurgery with 18 months of axial low back pain radiating into her hips and thighs, and 3 months of a House-Brackmann 3 right facial droop associated with left sided impaired pupillary constriction and anisocoria. Neurologic exam was otherwise normal. Genetic testing for NF-1 was negative. Brain imaging was normal. Spine imaging revealed an intradural mass associated with the left L3 nerve root. The patient was taken to surgery for resection of the mass. A lesion intrinsic to that nerve was identified and subtotally resected due to concern for iatrogenic injury. Postoperatively, the patient did not develop any new neurologic deficit. Pathologic diagnosis was grade 3 (FNCLCC score 6 of 8) malignant peripheral nerve sheath tumor. Staging CT/PET revealed 2 additional sites of disease in the nerve roots at C6/7 and C7/T1. Lumbar puncture was negative for malignant cells. The patient has subsequently initiated craniospinal proton beam radiotherapy. MPNSTs constitute 5-10% of all soft tissue sarcomas, with a peak incidence in the 7th decade of life. Up to half of these lesions are found in patients with neurofibromatosis type 1, in whom the peak incidence is in the 3rd or 4th decade. 19 cases of pediatric primary intradural MPNST have been previously reported. Surgical treatment is limited due to inability to achieve en bloc resection with wide margins within the intradural compartment. Outcomes have been poor, with 50% or less survival at 2 years despite aggressive multimodal therapies. Further optimization of adjuvant therapies is necessary to improve outcomes.
664 THE INCREASE IN POOR LIFESTYLE FACTORS IS A RISK FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEPATITIS C VIRUS INFECTION
Authors: S. Oeda, Y. Eguchi, T. Kohira, S. Kamachi, N. Furukawa, T. Kuwashiro, S. Nakashita, S. Iwane, Y. Ide, Y. Kawaguchi, T. Noda, I. Ozaki, T. Mizuta, R. Iwakiri, K. Anzai
Journal: Journal of Hepatology (2013)
New FDA Chief Stresses Enforcement and Quality
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article New FDA Chief Stresses Enforcement and Quality Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 11, 5 June 1991, Pages 744–745, https://doi.org/10.1093/jnci/83.11.744 Published: 05 June 1991