tbuckley/cabot-search huggingface dataset:
Abstract 4798: Cytotoxic T cells kill tumor cells in a contact and antigen-dependent manner, but the interaction affects neighboring, non-target cells via interferon gamma secretion
Authors: Nicholas SR Sanderson, Mariana Puntel, Greg Baker, Maria G. Castro, Pedro R. Lowenstein
Journal: Cancer Research (2010)

Abstract The interaction between cytolytic T cells and antigen presenting targets involves stable intercellular contacts known as immunological synapses. It has been postulated that one function of immunological synapses might be to restrict the effector functions of the T cell to the target cell, while protecting bystanders (non-target cells). We wished to test this hypothesis in the context of an anti-tumor immune response. To model the three-way interaction between T cells, target cells and bystanders, we used OT-I ovalbumin-specific T cells, GL26 murine glioma cells expressing ovalbumin, and wild type mouse astrocytes. We confirmed the formation of immunological synapses between T cells and GL26 cells, and assessed whether two effector functions of T cells, i.e., cytolysis and cytokine action, were limited to the post-synaptic target cells. We found that cytolysis was strictly restricted to the target tumor cells, but that the effect of interferon gamma, as measured by Stat1 phosphorylation, was more pronounced on the bystander astrocytes. We conclude that a likely model of cytotoxic T cell action in tumor immunity involves direct lysis of tumor cells, and interferon gamma action on the tumor stroma. Our data has implications for the development of improved anti-tumor imunotherapies which will target both the tumor cells and the tumor microenvironment. This work is supported by National Institutes of Health/National Institute of Neurological Disorders &amp; Stroke (NIH/NINDS) NIH/NINDS Grant 1R21-NS054143, 1UO1 NS052465 and 1RO1-NS057711 to M.G.C.; NIH/NINDS Grants 1 RO1 NS 054193, RO1 NS061107 and 1R21 NS047298 to P.R.L. 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 4798.
A1.5 Smoking is a risk factor for ACPA prior to onset of symptoms of rheumatoid arthritis in a cohort from southern europe
Authors: Alison J Cartwright, Anne-Marie Quirke, Paola de Pablo, Dora Romaguera, Salvatore Panico, Amalia Mattiello, Diana Gavrila, Carmen Navarro, Carlotta Sacerdote, Paolo Vineis, Rosario Tumino, Dominique Michaud, Elio Riboli, Benjamin A Fisher, Patrick J Venables
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is characterised by antibodies to citrullinated proteins (ACPA) which may be present several years before development of clinical symptoms. Smoking is a known risk factor for the development of RA, but data is scarce on the relationship of smoking with specific subsets of ACPA in the years before disease onset. In this study we examined the immune response to citrullinated antigens and a detailed smoking history, in a nested case-control study of subjects enrolled in the European Prospective Investigation into Cancer (EPIC) project who later developed RA. <h3>Materials and Methods</h3> The study sample included 412 participants from EPIC centres in Italy and Spain. Serum from 103 individuals who would eventually develop RA (pre-RA cases) were compared with three age-, sex- and centre-matched controls (n = 309). Antibodies to CCP, citrullinated-α-enolase peptide-1 (CEP-1; CKIHACitEIFDSCitGNPTVEC), citrullinated-fibrinogen (cFIB; CNEEGFFSACitGHRPLDKKC) and citrullinated-vimentin (cVIM; CVYATCitSSAVCitLCitSSVPC) were analysed by ELISA with positivity defined by 98<sup>th</sup> percentile of the controls. <h3>Results</h3> The median time to diagnosis in the pre-RA cases was 7 years (1.7–15.8 years). The frequency of positive antibodies (cases vs. controls) were: anti-CCP2 (20%; p &lt; 0.001), anti-cFIB (18%; p &lt; 0.001), anti-CEP-1 (15%; p &lt; 0.001), and anti-cVIM (6%; p &lt; 0.006). All of the antibodies increased in frequency closer to diagnosis and with no specificity being particularly prominent in very early presymptomatic autoimmunity. The frequency of ever smoking was higher amongst pre-RA cases compared with controls (59% vs. 47%, p = 0.02). Pre-RA cases who smoked had higher levels of ACPA by all measures, which reached statistical significance when comparing former smokers to other groups. Pre-RA former smokers were 2.5 times more likely to develop RA (OR 2.50, 95% CI: 1.28, 4.89; p = 0.007) and were four times more likely to have positive anti-CEP-1 (OR 4.06, 95% CI 1.02, 16.2) than pre-RA never smokers. <h3>Conclusions</h3> This is the first study of Pre-RA from a Southern European population in which we show that smoking is a risk factor not only for RA but for the development of presymptomatic autoimmunity, with citrullinated enolase being prominent. This strengthens the hypothesis that smoking is of aetiological importance in the very early stages of generating the autoantibodies that ultimately drive the disease.
Tc-99m MDP and Tc-99m MIBI in the Assessment of Spondyloarthritis Presenting as Bone Metastasis Before Treatment with Infliximab
Authors: Ali Hadi, Adil Al-Nahhas, Gillian Vivian, Peter Hickling
Journal: Clinical Nuclear Medicine (2002)

HADI, ALI M.B., Ch.B.*; AL-NAHHAS, ADIL M.Sc., F.R.C.P.†; VIVIAN, GILLIAN M.R.C.P., F.R.C.R.†; HICKLING, PETER B.Sc., F.R.C.P.* Author Information
Abstract 362: TR-FRET binding assays for PI3K family inhibitors
Authors: Sara B. Hereley, Jill K. Wolken, William J. Frazee, Hildegard C. Eliason, Steven M. Riddle
Journal: Cancer Research (2010)

Abstract There is a great clinical need to develop selective, high affinity kinase inhibitors. While many high throughput kinase activity assays have become readily available, easy-to-use and cost-effective, activity-based assays have significant limitations in terms of both the extent of target coverage and the type of information they can provide about compounds. We have developed a competitive TR-FRET binding assay platform for characterization of protein kinase inhibitors. This assay platform has several advantages over traditional activity-based assays, in part due to simplicity of the assays as well as the ability to measure binding events in real time. To extend the breadth of target coverage of this platform, we have developed novel tracers for Class I PI3-kinases and the related protein kinase mTOR. We present a comparison of inhibitor potencies measured in binding assays relative to kinase activity assays for a diverse set of commonly used PI3 kinase family inhibitors. These novel assays enable simple, rapid measurements of IC50 values for PI3 kinases and mTOR. 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 362.
Effect of Vitamin A Nutriture on Experimental Esophageal Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K M Nauss, D Bueche, P M Newberne
Journal: JNCI Journal of the National Cancer Institute (1987)

The effect of mild vitamin A deficiency or vitamin A supplementation on methylbenzylnitrosamine (MBN; CAS: 937-40-6)-induced esophageal carcinogenesis was examined in Sprague-Dawley rats. The animals were fed semipurified diets containing levels of retinyl acetate, which were adequate (2.2 mg/kg diet), deficient (0.30 mg/kg diet), or supplemented (29.9 mg/kg diet) with respect to vitamin A content. Carcinogen-treated rats received 2.5 mg MBN/kg (body wt) twice a week for 5 weeks; they were then sacrificed for evaluation of esophageal tumorigenesis 15 weeks later. Liver levels of retinol reflected vitamin A nutriture, but there were no clinical signs of deficiency or toxicity. There were no significant differences in the frequency or incidence of esophageal tumors (either carcinomas or papillomas) among the dietary groups. There was also no indication that either vitamin A deficiency or vitamin A supplementation influenced the formation of preneoplastic lesions. Although the time was short for the neoplastic development, tumors were observed. These data suggest that vitamin A is selective in tissues it may protect from cancer induction and that the esophagus is less involved than other tissues.
P1154 EFFECT OF VITAMIN D SUPPLEMENTATION ON SUSTAINED VIROLOGICAL RESPONSE TO PEGINTERFERON ALFA-2b/RIBAVIRIN COMBINATION IN CHRONIC HEPATITIS C GENOTYPE 4
Authors: M. Hassany, G. Esmat, M. El Raziky, W. Doss, D. Sabry, A. Ahmed, N. Assem, A. El Sharkawy, M. El Kassas
Journal: Journal of Hepatology (2014)
Worksite Cancer Education Programs Expanding
Authors: E. Taylor
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Worksite Cancer Education Programs Expanding Get access Ellen Taylor Ellen Taylor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 3, 5 February 1992, Page 146, https://doi.org/10.1093/jnci/84.3.146 Published: 05 February 1992
Studies of Human Myoglobin in Several Diseases of Muscle
Authors: Gerald T. Perkoff
Journal: New England Journal of Medicine (1964)

ALTHOUGH the clinical features, mechanisms of inheritance and classification of various forms of muscular dystrophy are well understood3 4 5 the pathogenesis of these disorders still is unknown. That alterations in the myoglobin content of muscle might be of primary importance in muscular dystrophy first was suggested by Meldolesi6 and later by Biorck,7 who noted that the concentration of myoglobin was low in these disorders. However, neither the properties of the myoglobin in muscle diseases nor the mechanism of the decrease in concentration is known.In the present study myoglobins isolated from several kinds of abnormal muscle have been compared to normal . . .
THU0526 Joint Distribution and Outcome in 331 Patients with Monoarthritis of Less Than 16 Weeks Duration: A Longitudinal Multicenter Cohort Study in Eastern Norway
Authors: E. S. Norli, G. H. Brinkmann, M. D. Mjaavatten, O. Bjørneboe, A. J. Haugen, H. Nygaard, T. K. Kvien, E. Lie
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cohort studies are essential to provide better understanding of the prognosis of acute monoarthritis, but few studies have focused on this issue. <h3>Objectives</h3> To describe the joint distribution in a cohort of patients with new-onset monoarthritis, and to study the outcome after two years, according to the initial joint involved. <h3>Methods</h3> 1084 patients (age 18-75 years) with arthritis of less than 16 weeks duration were included in the NOR-VEAC study from 2004 to 2010. Patients with crystal arthritis and osteoarthritis were not included. 354 patients (33%) had monoarthritis (clinical synovitis in one joint) at baseline. Follow-up data were available for 331 patients (94%), and 185 (52%) had 2-year follow-up data. <h3>Results</h3> Duration of joint swelling [median (25-75 percentiles)] among the 331 patients with monoarthritis was 22 (7-48) days, mean (SD) age 45 (14) years, 51.2% were females, 5.9% anti-CCP positive, 10.1% anti-CCP and/or RF positive). The most frequently affected joints were knees (50.5%), ankles (17.5%) and wrists (13.9%). 12 patients (3.6%) fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) at baseline; these had mostly wrist or small joint involvement. Two patients with clinical synovitis of the knee fulfilled the criteria as a result of one more tender joint. During follow-up 10 additional patients fulfilled the criteria, 8 of whom presented with large joint arthritis (table). No patients with ankle monoarthritis ever fulfilled the criteria, nor progressed to a clinical diagnosis of RA within 2 years of follow-up. 57 patients (17.2%) were diagnosed with reactive arthritis at baseline, 10 patients (3%) with psoriatic arthritis (PsA), and during follow-up only 4 more patients were classified as PsA. The patients diagnosed with PsA had monoarthritis of the knee (n=8), hand (n=2), wrist (n=2), elbow (n=1) and foot (n=1) at presentation. In addition two patients with arthritis of the knee and ankle were diagnosed with axial spondyloarthritis. In 236 patients (71%) the arthritis had resolved at last follow-up without DMARD treatment. 51 patients (15.4%) had DMARDs prescribed, 97 (29.3%) received intra-articular corticosteroids and 73 (22%) systemic corticosteroids. <h3>Conclusions</h3> Few patients with acute or recent onset monoarthritis seem to develop chronic inflammatory joint disease over two years. Patients with ankle monoarthritis had an especially low likelihood of developing RA or other chronic rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Abstract 2924: The role of autophagy in telomere damage-induced replicative senescence.
Authors: Florie Charles, Jayanta Debnath, Bradley Stohr
Journal: Cancer Research (2013)

Abstract Recent studies have implicated autophagy in multiple aspects of cancer biology, including oncogene-induced senescence (OIS) and genome instability. Autophagy is thought to control the transition to OIS through its ability to regulate the Senescence Associated Secretory Phenotype (SASP), which is necessary and sufficient for OIS. In addition, autophagy can suppress genome instability by limiting p62 accumulation in an apoptosis-deficient setting. In this study, we explored the role of autophagy in replicative senescence, an important barrier to tumorigenesis that is driven by telomere dysfunction and that is very distinct from OIS. We modeled replicative senescence by expressing mutant telomerase in human diploid fibroblasts, which rapidly induces telomere dysfunction and senescence. We observed strong induction of autophagic flux in response to telomere dysfunction prior to and during senescence. To determine the role of autophagy in the cellular response to telomere damage, we examined multiple components of the dysfunctional telomere response: transition and maintenance of senescence, SASP, DNA damage response, genome instability, and heterochromatin foci. In cells depleted of key autophagy mediators (ATGs), we did not observe a clear defect in the transition to senescence, as was previously seen with OIS. However, we did observe an outgrowth population of non-senescent cells among the senescent autophagy-deficient population, suggesting a possible defect in the maintenance of senescence. We also found that telomere dysfunction induced secretion of IL6 in an autophagy-dependent manner. Lastly, we observed an increase in polyploid cells in Atg7-deficient checkpoint-proficient cells, suggesting a role for autophagy in maintaining genome stability during the dysfunctional telomere response. Our results suggest that autophagy controls several aspects of the cellular response to telomere dysfunction in normal human cells. Citation Format: Florie Charles, Jayanta Debnath, Bradley Stohr. The role of autophagy in telomere damage-induced replicative senescence. [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 2924. doi:10.1158/1538-7445.AM2013-2924
AB0216 Serum Angiogenesis Markers and their Association with Ultrasound-Detected Synovitis in the Evaluation of Disease Activity in Juvenile Idiopathic Arthritis
Authors: J. Świdrowska, E. Smolewska
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Synovial angiogenesis, defined as a complex process of developing new blood vessels from the existing microvascular bed, is considered to be an important early step in the course and pathogenesis of juvenile idiopathic arthritis (JIA). <h3>Objectives</h3> To investigate the involvement of angiogenesis markers (VEGF, sVEGF-R1, sVEGF-R2, angiopoetin-1, angiopoetin-2) in early juvenile idiopathic arthritis and its possible relevance to disease activity and the degree of ultrasound-detected synovial inflammation and angiogenesis. <h3>Methods</h3> Serum levels of vascular markers were measured in 17 patients with juvenile idiopathic arthritis (aged 1,5-17) and 19 age-matched healthy controls. Ultrasound examination of inflamed joints was performed in each JIA patient and synovial angiogenesis was assessed by means of Power Doppler ultrasonography (PDUS) and the 4th grade vascularity scale. <h3>Results</h3> VEGF serum levels were significantly higher in JIA patients than in healthy controls (0,42±0,39 ng/ml vs 0,20±0,16 ng/ml; p&lt;0,05). The same sequence was observed for sVEGF-R1 and sVEGF-R2. Large variation of angiopoetin-1 and -2 levels in serum was observed in JIA patients and healthy controls. PDUS examination evaluated increased synovial microvascular blood flow in 16 of 17 patients (94%) <h3>Conclusions</h3> This pilot study has shown the high correlation between PDUS synovial microvascular blood flow, serum angiogenesis markers and clinical synovitis in JIA patients. It may indicate important role of synovial angiogenesis in pathogenetic mechanism of JIA. <h3>References</h3> Clavel G, Bessis N, Lemeiter D, et al. Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction, Clin Immunol. 2007 Aug;124(2):158-64 Spârchez M, Fodor D, Miu N. The role of Power Doppler ultrasonography in comparison with biological markers in the evaluation of disease activity in Juvenile Idiopathic Arthritis, Med Ultrason. 2010 Jun;12(2):97-103 Taylor PC. Serum vascular markers and vascular imaging in assessment of rheumatoid arthritis disease activity and response to therapy, Rheumatology. 2005 Jun;44(6):721-8 Salvador G, Sanmartí R, Gil-Torregrosa B, et al. Synovial vascular patterns and angiogenic factors expression in synovial tissue and serum of patients with rheumatoid arthritis, Rheumatology (Oxford). 2006 Aug;45(8):966-71 Strunk J, Heinemann E, Neeck G, et al. A new approach to studying angiogenesis in rheumatoid arthritis by means of power Doppler ultrasonography and measurement of serum vascular endothelial growth factor, Rheumatology 2004 September;43(12):1480-83 Ohrndorf S, Backhaus M. Advances in sonographic scoring of rheumatoid arthritis, Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii69-75 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3206
P197 The Incidence Of New Pseudomonas Aeruginosa Infection In Children With Cystic Fibrosis
Authors: F. Gilchrist, J. Belcher, A. Jones, D. Smith, A. Smyth, K. Southern, P. Spanel, A. Webb, W. Lenney
Journal: Thorax (2014)

<h3>Introduction</h3> Pseudomonas aeruginosa (PA) is one of the most important pathogens in cystic fibrosis (CF). Although there is a wealth of data about the prevalence of chronic PA infection, there is a paucity of evidence about the incidence of new PA infection. <h3>Methods</h3> The SPACE (Sensitivity and specificity of PA detection using the hydrogen Cyanide concentration of Exhaled breath) study investigated if exhaled breath hydrogen cyanide is an early marker of PA infection in children with CF. Breath samples, clinical data and microbiology samples were collected at each out-patient appointment from a large cohort of children with CF who had not isolated PA for &gt;12 months. This abstract reports the PA acquisition data. <h3>Results</h3> 233 children were followed for a median of 2.0 (1.7–2.3) years. The median (IQR) age was 8.0 (5.0–12.2) years. 71 children isolated PA during the study period. The incidence rate (95% CI) of new PA infections was 0.15 (0.10–0.22) cases per patient year for those that had never previously isolated PA and 0.19 (0.13–0.27) cases per patient year for those that had been free from PA for &gt;12 months. This rate varied between 0.08 (0.04–0.18) and 0.28 (0.14–0.49) cases per patient year at the 8 recruiting centres. 42% of children were asymptomatic at the time of PA acquisition. The median (IQR) number of antibiotic courses per patient year varied between the centres: 0.6 (0.2–1.3) to 3.6 (3.1–4.2) for oral and 0.0 (0–0) to 0.4 (0–1.2) for intravenous. <h3>Conclusions</h3> This is the first prospective study to report the incidence of new PA infection in a large cohort of children with CF, considered to be free of PA airway infection. Incidence rate was higher in children who had isolated PA previously. The variation between centres is not easily explained and needs further investigation. <h3>Acknowledgments</h3> We would like to thank the Principal Investigators, research nurses and co-ordinators at each of the recruiting centres as well as the children and their families.
Etiologic Heterogeneity of Neural-Tube Defects
Authors: Lewis B. Holmes, Shirley G. Driscoll, Leonard Atkins
Journal: New England Journal of Medicine (1976)

We classified 106 stillborn and live-born infants with anencephaly, meningomyelocele, meningocele and encephalocele according to the recognized causes of these malformations. Six different causes were identified, including both genetic and nongenetic disorders; 12 per cent had nongenetic disorders, a chromosome abnormality, or an encephalocele as part of the autosomal recessive Meckel syndrome. Therefore, for this 12 per cent genetic counseling normally provided for isolated anencephaly, meningomyelocele or encephalocele would have been incorrect. If all infants were considered together regardless of cause, the precurrence and recurrence rates of similar malformations in the sibs were 5.2 and 1.7 per cent respectively. However, if infants with other disorders, especially the Meckel syndrome, were excluded, the precurrence and recurrence rates for isolated anencephaly, meningomyelocele and encephalocele among white infants were only 1.7 per cent and 0 per cent. These rates are much lower than the risk of 5 per cent currently being used in genetic counseling in the United States.
767 PREDICTIVE ROLE OF SERUM HBsAg LEVEL IN GENOTYPE B OR C HBeAg-NEGATIVE CHRONIC HEPATITIS B PATIENTS UNDERGOING PEGINTERFERON THERAPY
Authors: C.-Y. Peng, H.-C. Lai, W.-P. Su, C.-H. Lin, P.-H. Chuang, J.-T. Kao, S.-H. Chen
Journal: Journal of Hepatology (2013)
Primary Chemotherapy Effect in Sentinel Node Detection in Breast Cancer
Authors: ADRIANO VIGÁRIO, M. T. SAPIENZA, A. P. SAMPAIO, J. R. PIATO, N. BARROS, A. BARROS, J. A. PINOTTI, C. A. BUCHPIGUEL
Journal: Clinical Nuclear Medicine (2003)

Purpose: Sentinel node (SN) biopsy is a reliable method for improved staging of breast cancer, offering an alternative to routine axillary dissection. Perhaps preoperative chemotherapy could increase the rate of false-negative SN because of induced lymphatic changes. The aim of the study was to evaluate the utility of lymphoscintigraphy and of hand-held probe detection in the SN approach after chemotherapy, correlating it with histologic analysis of the axilla. Methods: Eighty-three patients (mean age, 53 years; TNM stage I) were studied prospectively. They were separated into two groups: group 1 (G1), 37 patients with preoperative chemotherapy and group 2 (G2), 46 patients without chemotherapy. Mean tumor size was 2 cm in both groups. Lymphoscintigraphy was performed 3 to 4 hours after peritumoral injection of Tc-99m dextran-70 in a 0.2-ml volume and activity of 14.8 MBq (0.4 mCi), performed under ultrasound or mammographic control. On the following day, each patient underwent tumor resection with axillary dissection, included the SN. Results: The SN was detected by scintigraphy in 78 patients (94%). The failure of SN to predict the axillary histologic status was significantly higher (P= 0.01) in G1 than in G2 (7 and 1 false-negative result, respectively). Conclusion: Preoperative chemotherapy seems to impair axillary evaluation by SN biopsy and should be used cautiously in this subset of patients.