tbuckley/cabot-search huggingface dataset:
Abstract 4785: Silver nanoparticles induce apoptosis in squamous lung cancer cell by regulation of cyclic AMP response element-binding protein: regulating its upstream oxidative stress-dependent Ras signaling pathways
Authors: Hee Sun Park, Sunhyae Jang, Hye Rim Cha, Sun Young Jeong, Jeong Eun Lee, Ju Ock Kim, Ja Seok Koo, Sun Young Kim
Journal: Cancer Research (2011)

Abstract Recently, much effort has been devoted to the development of biomedical applications (drug delivery system and as therapeutic drugs themselves) for nanoparticles (NPs). Silver NPs have been shown various therapeutic effects such as antimicrobial, antioxidant, and anti-inflammatory effects. Recently silver NPs have been shown to induce cytotoxicity in cancer cells. But exact mechanism is not yet established. We conducted this study to determine the mechanisms of silver NPs on cellular apoptosis in non-small cell lung cancer (NSCLC) cell lines using cyclic AMP response element-binding protein (CREB) activity which has been implicated to contribute an important pathobiologic role in lung carcinogenesis and is considered a potential therapeutic target for NSCLC. We hypothesized that constitutively increased CREB and its related signaling pathways can be blocked by silver NPs and it might be by regulation of oxidative stress in tumorigenesis. In H520 cell, human lung squamous cancer cell line, reactive oxygen species (ROS) were increased. In western blot analysis, Ras signaling molecule in which ROS is involved was constitutively overexpressed and the levels of pErk, pRsk, pAkt and pCREB were increased in H520 cell. Incubation of the H520 cells with silver NPs (at dose of 100 or 200 μM) substantially suppressed the ROS in H520 cell and Ras-Erk-Rsk-CREB and Ras-PI3K-Akt signaling pathway in a dose-dependent manner. We subsequently demonstrated that silver NPs inhibited the caspase-dependent pathway, determined by increased levels of PARP (poly (ADP-ribose) polymerase) cleavage. In this study, we suggest that silver NPs induce apoptosis in human lung cancer cells by attenuation of oxidative stress in lung cancer cell line and ROS-dependent Ras signaling which involves CREB signaling pathways and may be useful as a therapeutic strategy for 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 4785. doi:10.1158/1538-7445.AM2011-4785
Correction of Human Cyclic Neutropenia with Prednisolone
Authors: Daniel G. Wright, Anthony S. Fauci, David C. Dale, Sheldon M. Wolff
Journal: New England Journal of Medicine (1978)

A 70-year-old woman with cyclic neutropenia was treated with 16 mg of etiocholanolone and 25 mg of prednisolone intramuscularly every other day. During 14 weeks' treatment amplitude of cyclic fluctuations in neutrophil counts gradually decreased, but pretreatment cycles returned promptly after treatment was stopped. Prednisolone alone every other day (25 mg) reproduced this result, and by 23 weeks, neutrophil counts became stable at about 1500 per cubic millimeter. Cycling of monocytes, platelets and reticulocytes was also eliminated, as were symptoms that had accompanied neutropenic periods. In addition, bone-marrow neutrophil precursors and neutrophil marrow reserves were stabilized. The patient was subsequently maintained satisfactorily with oral prednisolone, 20 mg every other day. These studies demonstrate that the discontinuous myeloid maturation that occurs in cyclic neutropenia can be corrected with prednisolone every other day. (N Engl J Med 298:295–300, 1978)
PMO-032 Validation of a food frequency questionnaire for estimating calcium intake in young female adults
Authors: R Cawley, M Mackenzie-Fraser
Journal: Gut (2012)

<h3>Introduction</h3> The relatively low cost and low respondent burden of a Food Frequency Questionnaire (FFQ) that effectively and rapidly identifies individuals with low calcium intakes would be a valuable asset to clinical dietetics. Young female adults (age 18–30 years) tend to have a lower calcium intake which may increase their risk of osteoporosis in later life. This study aimed to examine the validity and reliability of a non-quantitative calcium FFQ by comparing the mean calcium intake measured by the FFQ with that measured by a 7 day weighed food diary. <h3>Methods</h3> The validity and reliability of non-quantitative calcium FFQ was evaluated. A self-administered FFQ was administered to 41 Caucasian female participants, aged 18–26 years, studying at the Robert Gordon University, Aberdeen. A points system was used to assess whether the individual was meeting their recommended calcium requirement. A paired <i>t</i> test measured the difference between the mean calcium intake measured by the food diary and the FFQ. <h3>Results</h3> The mean calcium intake estimated by the FFQ and the 7 day weighed food diary was 622.0±138.3 mg/day and 692.5±188.1 mg/day, respectively. A paired <i>t</i> test revealed a significant difference of 70.6±78.1 mg/day between the calcium intake measured by the FFQ and the food diary (<i>P</i>r=0.931, p &lt; 0.05) <h3>Conclusion</h3> A small but significant difference of 70 mg/day was found between the calcium intake measured by the FFQ and the 7-day food diary. However, this significant result did not reflect the precision between the two methods at estimating calcium intake. Both Pearson9s correlation coefficient and Bland Altman procedures demonstrated good agreement and validity. The FFQ identified individuals with low calcium intakes; however, the degree of underestimation by the FFQ increased when calcium intake increased. Although the FFQ may not be as accurate as a 7-day weighed food diary when estimating absolute calcium intake it appears to be an effective method of rapidly identifying individuals with low calcium intake. This easily utilised calcium FFQ could be a valuable and useful clinical tool in identifying individuals with calcium deficient diets. Furthur research into whether this FFQ is a reliable method of identifying low calcium intakes in other subgroups of the population is recommended. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Bates B</b>, Lennox A, Swan G. <i>National diet and nutrition survey.</i> London: Department of Health, 2009. 2. <b>Salvini S</b>, <i>et al.</i> Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. <i>Int J Epidemiol</i> 1989;<b>18</b>:858–67. 3. <b>Tefft M</b>, Boniface D. Estimating food and nutrient intake from food frequency questionnaire data by reference to a standard weighed diet survey. <i>J Hum Nutr Diet</i> 2000;<b>13</b>:219–24.
P1120 PREDICTION OF SUSTAINED VIROLOGIC RESPONSE IN TREATMENT-NAIVE CHRONIC HEPATITIS C GENOTYPE 1 PATIENTS TREATED WITH TELAPREVIR PLUS PEGYLATED INTERFERON AND RIBAVIRIN IN PHASE 3 TRIALS
Authors: S. Zeuzem, R. Demasi, G.R. Foster, M. Buti, A. Baldini, D. Luo, J. Witek, M. Rizzetto
Journal: Journal of Hepatology (2014)
The Infant of the Diabetic Mother
Authors: Ilene R. Sosenko, John L. Kitzmiller, Sherry W. Loo, Petra Blix, Arthur H. Rubenstein, Kenneth H. Gabbay
Journal: New England Journal of Medicine (1979)

C peptide is secreted by pancreatic beta cells in amounts equimolar with insulin, and its levels provide a direct indication of endogenous fetal levels of insulin despite the presence of maternal insulin antibodies. To determine the presence of hyperinsulinemia and its relation to the development of complications in infants of diabetic mothers, we measured cord serum levels of C peptide in 79 infants of diabetic mothers and 62 infants of nondiabetic mothers. Infants of diabetic mothers had higher cord levels of C peptide, which were significantly associated with neonatal hypoglycemia and macrosomia (P less than 0.001) but not with hyaline-membrane disease. Cord levels of C peptide in infants of diabetic mothers were elevated at the earliest gestational age studied (less than 34 weeks) and were directly related to the severity of maternal diabetes, as assessed by the White classification. We conclude that hyperinsulinemia is present in infants of diabetic mothers and that it is related to some major complications in such infants.
Lipoprotein Lipase Inhibition in the Hyperlipemia of Acute Alcoholic Pancreatitis
Authors: Jacques I. Kessler, Jared C. Kniffen, Henry D. Janowitz
Journal: New England Journal of Medicine (1963)

HIGH concentrations of particulate triglycerides impart a characteristic milky turbidity to the blood serum known as lactescence.1 Lactescence of the serum in acute pancreatitis, supposedly a rare manifestation of this disorder, was first reported in 1865.2 In more recent publications, however, hyperlipemia was noted in 4 to 8 per cent,3 4 5 and in a report from this institution,6 the incidence of serum lipid aberrations during the course of acute pancreatitis was found to be 53 per cent. Although different mechanisms have been offered to explain the transient hyperlipemia accompanying acute pancreatitis in man and laboratory animals7 the relation between pancreatitis and . . .
PTU-142 How Common are Delays in Referral of Patients with Oesophageal Cancer from Primary Care?
Authors: D Cheung, N Trudgill
Journal: Gut (2013)

<h3>Introduction</h3> The UK has the highest age-standardised incidence of oesophageal cancer (OC) in Europe with a 5 year survival rate of only 11.6%. We have investigated a large primary care cohort to determine how common delays in referral are and associated factors. <h3>Methods</h3> All subjects with OC from the Health Improvement Network (THIN) primary care database were studied. THIN includes over 6 million patients and is regionally and demographically representative of the UK. A nested case-control study was performed with cases of ‘delayed referral’ defined as subjects who met NICE guidance for urgent referral (August 2004) with alarm upper gastrointestinal (UGI) symptoms (dysphagia, weight loss, abdominal mass, recurrent vomiting, UGI bleed, iron deficiency anaemia) or dyspepsia over 55 years but were not referred within 14 days. Control subjects were referred within 14 days. Logistic regression analysis assessed associations with delayed referral. <h3>Results</h3> 4210 subjects had OC diagnosed after August 2004. 567 (377 (66.5%) male) had a referral date recorded and were analysed. Mean age 70.7 ± 11.2 years with 1.4 ± 0.8 mean consultations prior to referral. Presenting symptoms of OC: dysphagia 326 (57.5%), dyspepsia 174 (30.7%), anaemia 31 (5.5%), weight loss 23 (4.1%), recurrent vomiting 6 (1.1%), UGI bleed 6 (1.1%) and abdominal mass 1 (0.2%). 355 (62.6%) referred within 14 days with mean lag time of 1.9 ± 3.0 days. 212 (37.4%) had a potential referral delay: 60 (10.6%) 14–29 days; 103 (18.2%) 30 days-1 year; 49(8.6%) &gt; 1 year; with mean lag time of 273.0 ± 433.1 days. Time from presentation to OC diagnosis in the controls was 63.8 ± 155.1 days compared with 3413 ± 469.7 days in the delayed referral group, with 0.8 ± 0.9 extra consultations prior to referral. There was no difference in age at presentation (70.2 ± 11.0 years (delayed referral), 70.2 ± 11.3 years (controls), P = 0.5) and no association with male gender (1.15 (95%CI 0.8–1.6), p = 0.46) or Townsend index (group 1–2 versus group 4–5, 0.95 (95%CI 0.6–1.4), p = 0.8) for referral delay. Subjects with dysphagia were less likely to experience referral delay (0.15 (95%CI 0.1–0.2), p = &lt; 0.0001) compared with other alarm symptoms. However, delayed referral did not significantly affect oesophagectomy rate (14.6% vs 16.9%, 0.72 (95%CI 0.4–1.2), p = 0.18) or 1 year survival (43.8% vs 44.1%, 0.98 (95%CI 0.7–1.5), p = 0.95). <h3>Conclusion</h3> A third of patients were not promptly referred to secondary care despite meeting NICE criteria leading to diagnosis delays. 80% of subjects with dysphagia were referred promptly, but only 39% of subjects with other alarm symptoms or new dyspepsia. Surprisingly, delayed referral did not affect surgical resection or 1 year survival rate. <h3>Disclosure of Interest</h3> None Declared
B-cell lymphoma in a tubular adenoma with high-grade dysplasia: a rare extramedullary manifestation of high-grade diffuse large B-cell lymphoma
Authors: E. Roeb, M. Rummel, W. Blau, B. Etschmann, S. Gattenlöhner
Journal: Endoscopy (2011)

B-cell lymphomas represent about 90 % of all non-Hodgkin lymphomas (NHLs). Almost all express pan B-cell antigens including CD19, CD20, and PAX5. Most patients with NHL present persistent painless peripheral lymphadenopathy. Staging tests do not include colonoscopy. Here we present a rare case of synchronous occurrence of a high-grade diffuse large B-cell lymphoma (DLBCL) initially presenting in a tubular adenoma of the large bowel and subsequently in the bone marrow.
Jejunogastric intussusception causing gastrointestinal bleeding
Authors: S. Chowdhury, A. Dutta, S. Pal, R. Leena, A. Chacko
Journal: Endoscopy (2011)

A 66-year-old man presented to the emergency room with history of hematemesis without melena or postural symptoms. He complained of diffuse, crampy abdominal pain with no specific aggravating or relieving factors. He had undergone surgery for a bleeding ulcer 22 years ago, details of which were not available. On examination, he was pale and there was a firm mass with ill-defined margins in the left lumbar region. Investigations revealed low hemoglobin (7.3 gm/dL) and gastroscopy revealed a large, congested mass occupying the body and antrum of the stomach ([Fig. 1]).
Absence of Sex Bias in the Referral of Patients for Cardiac Catheterization
Authors: Daniel B. Mark, Linda K. Shaw, Elizabeth R. DeLong, Robert M. Califf, David B. Pryor
Journal: New England Journal of Medicine (1994)

It has been suggested that women with clinical evidence of coronary artery disease are less often referred for cardiac catheterization than are men. To determine whether there is sex-related bias in referral for cardiac catheterization, we prospectively studied a cohort of 410 symptomatic outpatients (280 men and 130 women) who were being evaluated with exercise testing for possible coronary artery disease.
Abstract 1222: Met-dependent positive and negative signaling cascades in gastric cancer cells
Authors: Andrea Z. Lai, Hong Zhao, Sean Cory, Emily S. Bell, Michael Hallett, Morag Park
Journal: Cancer Research (2012)

Abstract Signaling by the Met, hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) activates multiple downstream signaling pathways that promote cell migration and invasive growth. Cells that overexpress and are “addicted” to Met also require Met signaling to sustain cell survival. Thus, a number of specific small-molecule inhibitors have been developed to target Met in the clinic. Although several successes of RTK-targeted therapies are acknowledged, several have limited long-term success clinically, due to development of drug resistance. Initiation of RTK signaling cascades leads to the activation of a number of downstream signaling molecules, but prolonged activation also triggers negative feedback loops that function in part to abrogate this signaling. Hence, targeted inhibition of Met, in addition to suppressing Met-dependent signaling, may also release cells from negative feedback mechanisms and allow the reactivation of signaling pathways, that may promote resistance to Met inhibition. As MET amplification occurs in 10-20% of gastric cancers, to identify core Met dependent signaling pathways activated in Met dependent cancers we have used four different gastric cancer cell lines that exhibit amplification, overexpression, and constitutive activation of Met. Upon inhibition of Met with a small-molecule inhibitor, we observe abrogation of several downstream signaling pathways at both the protein phosphorylation and transcript level. Interestingly, as Met has been demonstrated to cross-talk with the EGF receptor family, we also observe a decrease in the phosphorylation of EGFR and HER3 upon treatment with Met inhibitor, and a decrease in expression of EGFR ligands. Conversely, Met inhibition results in an elevation in expression of HER3 transcript and protein in all 4 cell lines, implicating Met signaling in HER3 repression, and inhibition of Met may release HER3 from this negative regulation. As increases in HER3 phosphorylation and expression occur in other models (such as breast or lung cancer cell lines) upon treatment with EGFR, HER2, or AKT inhibitors, and high HER3 expression is strongly associated with tumor progression and poor prognosis in gastric cancer; hence, the loss of negative regulation of HER3, downstream from Met, may ultimately contribute to clinical efficacy, or lack thereof, of Met inhibitors. 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 1222. doi:1538-7445.AM2012-1222
Controversies: Is it time to stop searching for MRSA? (Screening is still important)
Authors: B. Cookson
Journal: BMJ (1997)

Health care increasingly emphasises the team approach in which doctors, nurses, and other health workers adapt and develop new skills.Before changes of this kind are widely accepted, however, there must be clarity about the training, status, authority, working relationships, career structure, and remuneration of those who undertake responsibilities well beyond their traditional roles.
SC-35 * BMP SIGNALING REGULATES A QUIESCENT CANCER STEM CELL PHENOTYPE RESPONSIBLE FOR TREATMENT RESISTANCE IN GLIOBLASTOMA
Authors: M. Wu, N. Fernandez, A. Celebre, M. Srikanth, J. Kessler, J. Karamchandani, S. Das
Journal: Neuro-Oncology (2014)

Stem cell niches must be dynamic to enable stem cells to respond promptly and appropriately to physiologic demands. There is growing evidence to suggest that the superfamily of transforming growth factor-βs (TGF-βs) play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems. In glioblastoma, TGF-β has been shown to act as an oncogenic factor through its induction of self-renewal and proliferation in glioma stem cells (GSCs), and inhibition of GSC differentiation. Conversely, treatment of GSCs with BMP4 in vitro was found to direct these cells toward a differentiated, astrocytic phenotype, and abolish their ability to drive tumor growth following xenotransplantation. These studies suggest that TGF-β and BMP signaling direct glioma cells toward an irreversible fate choice, and that maintenance of the cancer stem cell (CSC) phenotype is necessary for tumorigenicity. We postulated that the CSC fate choices in glioblastoma are plastic, and that TGF-β and BMP signaling regulate cell glioma cell dynamics within the tumor microenvironment, as in cellular reprogramming. Further, we postulated that TGF-β and BMP might construe cell identities in glioblastoma that could be relevant to glioblastoma treatment resistance, disease evolution and disease progression. Here, we demonstrate that TGF-β and BMP signaling are active in the glioblastoma microenvironment, and regulate the shuttling of GSCs from an activated to a quiescent phenotype. At the molecular level, this process is mediated, as in EMT/MET, by the ZEB1/miR-200 double-negative feedback loop. Activation of p21 via BMP signaling is one mechanism for resistance to chemotherapy- and radiation-induced cell damage. Quiescent, BMPhi cells then give rise to TGF-βhi GSCs that drive tumour progression. Our findings demonstrate a role for BMP-mediated quiescence in glioblastoma disease resistance and recurrence, and suggest that targeted inhibition of BMP during chemoradiation could favorably alter the natural history of this disease.
THU0312 Reduction of concomitant treatment upon therapy with etanercept in juvenile idiopathic arthritis:
Authors: G. Horneff, K. Minden
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Combination treatment of Etanercept with corticosteroids and/or Methotrexate has been shown to have an impact on the occurrence of adverse events. (1) <h3>Methods</h3> The data base of the German BIKER registry documenting the treatment of juvenile idiopathic arthritis patients (JIA) with Etanercept since 2001 has been used to analyse the impact of treatment on the discontinuation of concomitant drug treatment, especially of corticosteroids, NSAIDs, Methotrexate and further DMARDs. <h3>Results</h3> 1276 JIA patients have been identified with a baseline visit and at least 1 follow up visit. At baseline, 1039 (81.4%) received NSAIDs, 582 (44%) received corticosteroids (median dosage 5 mg/day) and 928 (72.7%) received Methotrexate. 233 (18.3%) received other DMARDs (Azathioprine (5.5), Cyclosporine A (2.3%), Leflunomide (2.3%), Sulfasalazin (4.2%), (OH)Chloroquine (2.1%) as further concomitant treatment. Upon treatment, concomitant pharmacomedical treatment was continuously reduced over time (table). At 12 months 53% of patients received NSAIDs, and 58.9% Methotrexate, 29.3% corticosteroids. In total, 445/928 (48%) patients discontinued Methotrexate with a mean survival of combination with MTX of 34.5 months. 260/582 (45%) of patients discontinued corticosteroids with a mean survival of combination with corticosteroids of 26.5 months. So, corticosteroids have significantly earlier been discontinued than Methotrexate (p=0.006, Hazard ratio 1.2 (1.0-1.4). Of those 83 patients with uveitis as co morbidity, 35 (42%) discontinued MTX with a mean survival of MTX of 43 months. <h3>Conclusions</h3> Upon treatment with Etanercept, most patients initially received concomitant treatment with NSAIDs, corticosteroids, Methotrexate, and other DMARDs. However these drugs are frequently discontinued, while corticosteroids were discontinued prior to Methotrexate. <h3>References</h3> Horneff G, De Bock F, Foeldvari I, et al: Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis. 2009 Apr;68(4):519-25. <h3>Disclosure of Interest</h3> G. Horneff Grant/Research support from: Pfizer, Abbott, K. Minden: None Declared
Enlarged Spleen with a Heterogeneous Pattern
Authors: Rosa Nouvini, Sanjaykumar Hapani
Journal: New England Journal of Medicine (2013)

A 50-year-old man with a history of warm-antibody autoimmune hemolytic anemia and splenomegaly presented with fatigue of 2 weeks' duration and recent onset of jaundice. Physical examination revealed scleral icterus, conjunctival pallor, and splenomegaly.