tbuckley/cabot-search huggingface dataset:
P652The cardioprotective effect of exogenous sphingosine-1-phosphate requires the activation of endogenous sphingosine-1-phosphate via the sphingosine kinase 1
Authors: S Pedretti, MA Frias, RW James, S Lecour
Journal: Cardiovascular Research (2014)

Purpose: Exogenous administration of sphingosine-1-phosphate (S1P) alone, or as part of high density lipoprotein, protects against myocardial infarction. S1P-induced cardioprotection targets the inhibition of the mitochondrial permeability transition pore via mechanisms that remain unclear. In the cell, the endogenous production of S1P from sphingosine is dependent on the activation of sphingosine kinases (SphK) 1 and 2. These two kinases play a role in cardioprotection against ischemia-reperfusion (IR) injury. Therefore, we hypothesised that the cardioprotective effect of exogenous S1P requires the activation of endogenous S1P via SphK. Methods: Isolated cardiomyocytes from adult wildtype mice were exposed to 2 hours of simulated ischemia (SI) in the presence of S1P (10nM) with/without N,N-dimethylsphingosine (DMS, a SphK1 and 2 inhibitor, 10μM) or SKI (a specific SphK1 inhibitor, 15μM). Cell viability was assessed using trypan blue staining and normalised to the normoxic control. Isolated perfused hearts from adult wildtype mice were exposed to 35 minutes of global ischemia followed by 45 minutes of reperfusion (IR) in the presence of S1P (10nM) with/without SKI (10μM). Infarct size (IS) was assessed using tripheyltetrazolium chloride staining and SphK1 activity using a specific biochemical fluorescence based assay kit. Both parameters were normalised to the IR control. Results: In isolated cardiomyocytes, viability under normoxic conditions was 76±1%. SI reduced viability to 52±1% (p< 0.001 vs. normoxia). Pre-treatment with S1P restored the viability to 75±1% (p<0.001 vs. SI). The beneficial effect of S1P was partially inhibited in the presence of DMS (67±4%) (ns vs. S1P) and totally abrogated with SKI pre-treatment (54±2%). Similarly, pre-treatment with S1P in isolated hearts reduced IS following IR from 50±1% (IR control) to 31±2% (S1P) (p<0.001 vs. control). Pre-treatment with SKI abrogated the cardioprotective effect of S1P (56±8%) (p<0.05 vs. S1P) as well as the S1P-induced increase in SphK1 activity (from S1P: 196±79 arbitrary units (AU) to SKI+S1P: 53±27 AU, p<0.05 vs. S1P). Conclusions: Our data, performed in both isolated cardiomyocytes and isolated hearts subjected to an ischemia/reperfusion insult, strongly suggest that exogenous sphingosine-1-phosphate-induced cardioprotection is dependent on the activation of endogenous sphingosine-1-phosphate via sphingosine kinase 1.
TCT-705 Trascatheter Aortic Valve Implantation Outcomes With Self-Expandable and Balloon-Expandable Devices in Patients with Mixed Aortic Valve Stenosis
Authors: Gennaro Giustino, Matteo Montorfano, Eustachio Agricola, Alaide Chieffo, Vasileios F. Panoulas, Filippo Figini, Pietro Spagnolo, Azeem Latib, Ottavio Alfieri, Antonio Colombo
Journal: Journal of the American College of Cardiology (2014)
459 INSULIN RESISTANCE AND HIGH CHOLESTEROL LEVELS ARE ASSOCIATED WITH VITAMIN D DEFICIENCY IN HCV, HIV AND HIV/HCV COINFECTED PATIENTS
Authors: M.P. Gonzalez, G.B. Klautau, D.F. Mazo, R.S. Nogueira, M.C.J. Mendes-Correa, F.J. Carrilho, M.G. Pessoa
Journal: Journal of Hepatology (2013)
PTH-110 Are we Doing Enough Vaccinations? – a Dgh Experience of Patients on Biologics
Authors: S Vinnamala, M Khan, F M Shahid, G Moran, M Kwok, L Ulrich, L Field, R Cooney
Journal: Gut (2013)

<h3>Introduction</h3> Immunomodulators (IM) and biological agents are now used more often and earlier in Inflammatory Bowel Disease (IBD) leading to an increase in opportunistic infections (OI<sup>)1.</sup> European Crohn’s and Colitis Organization (ECCO) recommends screening and vaccinations for Varicella Zoster Virus (VZV) (if no history of chickenpox/shingles and serology negative), Human Papilloma Virus (HPV) - in women, Annual Influenza (inactivated vaccine), Pneumococcus (3- 5 yearly) and Hepatitis B (if HBV seronegative) in immunocompromised IBD patients. <h3>Methods</h3> We retrospectively collected the data on the serology status for Hep B&amp;C, VZV of our patients receiving biologics from pathology results reporting system and Chest X-ray (CXR) results from PACS. BCG vaccination status and previous Chicken pox exposure was obtained from the clinic letters. The information on the vaccination status was obtained by contacting the general practioners via telephone and from patients at attendance for their infliximab infusions. Data was also taken from the clinic letters and IBD MDT proformas. <h3>Results</h3> Of the 37 patients who are currently receiving biologics (18 males; 19 females; mean age: 37.3±2.3 years), 31 had Crohn’s disease, 5 UC and 1 indeterminate colitis. All patients received anti-TNF therapy with 33(91.7%) exposed to combination therapy with azathioprine (27) (81.8%) and (6) (18.2%) with methotrexate. Serology status on Hep B, C and Varicella was available in 26(77%), 5(13%), and 21(56%) patients respectively. A CXR was done in 65% of patients with 5 patients having their BCG status documented. IGRA was done on 2 patients with ambiguous mantoux results. Influenza, pneumococcal, HPV vaccines were administered in 6 (16.2%), 4 (10.8%) and 1 patients (2.7%) respectively. <h3>Conclusion</h3> Relevant serology status and vaccination history was available/recorded in a minority of patients only. Non/poor-adherence to guidelines, poor documentation or limits of data collection may explain this. To improve compliance information leaflets on the ECCO-recommended vaccines are being sent to GPs and patients. Adherence to checklists prior to biologic administration is enforced. We believe patient education with support of our IBD nurses and empowering patients with relevant personalised information given at diagnosis and during their treatment may increase the uptake of vaccinations in these high risk patients. The development of a dedicated IBD database ideally with GP links to allow vaccinations records to be accessed will allow us to audit our practise accurately and determine the efficacy of the current recommendations. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Toruner M<i> et al.</i> Risk factors for opportunistic infections in patients with IBD. Gastroenterology. 2008; 134:929–36
OP13 * IDENTIFICATION OF GENES EPIGENETICALLY DEREGULATED IN BRAIN METASTASIS FROM PRIMARY BREAST TUMOURS
Authors: R. P. Pangeni, K. Ashton, C. Walker, T. Dawson, C. Davis, F. Latif, J. L. Darling, T. J. Warr, M. R. Morris
Journal: Neuro-Oncology (2014)

INTRODUCTION: Brain metastases pose many challenges in terms of prognosis, complexity of tumour biology and tumour evolution. Here, we have analysed epigenetically deregulated candidate metastatic suppressor genes in metastatic brain tumours that evolved from primary breast tumours. Identified genes may be useful as prognostic markers that could be used to predict the risk of brain metastases from breast tumours or provide novel therapeutic targets. METHOD: We screened 80 genes that are epigenetically deregulated in cancer but not frequently methylated in primary breast tumours. These genes were identified by interrogating The Cancer Genome Atlas and a broad literature review. We analysed these genes for promoter methylation in metastatic brain tumours and their associated primary breast tumours. We carried out tumorigenicity assays to investigate the role of these genes in invasion and metastasis. RESULTS: We identified five genes (BNC1, CCDC8, L3MBTL1, GALNT9 and mir127), which are infrequently methylated in primary breast tumours and frequently methylated in brain metastases. In vitro migration and invasion assays indicate that these genes contribute to the metastatic potential of breast cancer cell lines. CONCLUSION: We have identified a number of genes that may contribute to breast to brain metastasis. Two of which (BNC1, GALNT9) are methylated and silenced specifically in the brain metastasis, indicating an event that has occurred after the tumour has disseminated. Another three genes (CCDC8, L3MBTL1 and mir127) are methylated in primary tumours that metastasised to the brain indicating a potential early role in metastasis. These findings may help develop prognostic and therapeutic tools.
IMCT-06SURVIVAL GAIN AND IMMUNE RESPONSE IN GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY BEFORE AND DURING ADJUVANT TEMOZOLOMIDE
Authors: Gaetano Finocchiaro, Marica Eoli, Serena Pellegatta, Elena Anghileri, Simona Frigerio, Bianca Pollo, Valeria Cuccarini, Carlo Antozzi, Francesco Acerbi, Lucia Cuppini, Paola Porrati, Sara Pessina, Maura Servida, Stefania Cuzzubbo, Paolo Ferroli, Maria Grazia Bruzzone, Renato Mantegazza, Eugenio Parati
Journal: Neuro-Oncology (2015)

Dendritic cell (DC) immunotherapy is gaining momentum in clinical cancer immunotherapy.We set-up a phase I-II study in patients with first diagnosis of glioblastoma (GBM) in which DC immunotherapy was associated to standard radiochemotherapy.The primary goal was to evaluate progression free Overall survival
PWE-017 Can we use blood markers instead of routine contrast swallows to predict anastomotic dehiscence after oesophageal resection?: Abstract PWE-017 Table 1
Authors: N Tewari, J A Catton, N T Welch, S L Parsons
Journal: Gut (2012)

<h3>Introduction</h3> Resectional surgery for oesophageal cancer is associated with significant risk of anastomotic dehiscence. In the era of enhanced recovery after surgery (ERAS), some anastomotic leaks may not present until after the patient is discharged home. This study aims to identify markers which may predict likelihood of anastomotic dehiscence. <h3>Methods</h3> All patients undergoing oesophageal cancer resection from January 2001 to November 2011 were identified from the Upper GI database where data is recorded prospectively. Retrospective review of patient demographics, operation type, radiology, blood results, histology, length of stay and mortality was performed. Blood results of patients with clinical evidence of anastomotic leak and 50 matched controls were collected for the first 10 post-operative days. <h3>Results</h3> 309 patients (median age 66 years) underwent oesophageal resection during this period. In-hospital mortality occurred in 22 patients (7.1%). 216 patients (69.9%) underwent routine contrast studies and 12 radiological leaks were identified. Two patients with radiological leaks had clinical findings suggestive of anastomotic leak, all were managed conservatively. Anastomotic leakage occurred in a further 20 patients. 13 of these should have undergone contrast swallow at day 7 according to the protocol at the time. Two had contrast swallows at day 7, which were normal, but subsequently leaked. 16 patients demonstrated clinical deterioration at days 2–7 which prompted either imaging with CT, endoscopy or surgical exploration. Two patients were never fit enough to undergo contrast study. The overall mortality in patients with leak was 5/32 (15.6%). Results of mean white cell count on days 1 to 9 are given in the Abstract PWE-017 table 1 below. There was a significant difference in white cell count from days 6 to 9 between the control group and leak group. There was a difference in mean CRP in the control group (163.91 mg/l) compared to the leak group (267.13 mg/l), p=0.00021. There was no significant difference in mean albumin between groups. <h3>Conclusion</h3> Routine contrast swallows are of limited value following oesophageal cancer resection. If there is suspicion of anastomotic leakage, radiology and endoscopy can be utilised. The finding of raised inflammatory markers in the absence of other causes is associated with anastomotic leakage and should be further investigated. In the clinically well patient with normal blood results, ERAS can be safely implemented after oesophageal cancer resection. <h3>Competing interests</h3> None declared.
O2.07 * FIRST 100 VESTIBULAR SCHWANNOMAS TREATED WITH GAMMA KNIFE IN SPAIN: LONG-TERM OUTCOME
Authors: P. de Andres, A. L. Presti, M. E. Kusak, N. Martinez, J. M. de Campos, R. Martinez
Journal: Neuro-Oncology (2014)

INTRODUCTION: Gamma Knife radiosurgery (GKRS) has become an established treatment option for vestibular schwannomas (VS). The aim of this study was to investigate long-term results regarding tumor volume control, neurological deficits outcome, effectiveness or treatment failure requiring surgery or reirradiation. METHODS: Data from the cohort of the first 100 consecutive patients with a sporadic VS diagnosis (not Neurofibromatosis 2 related SV) treated with GKRS at our Unit between 1993 and 1997 were retrospectively reviewed from a prospectively maintained database. Six were purely intracanalicular and 94 extended into the cerebello-pontine angle, with an average volume larger than the global cohort of 877 VS. The median age at the time of treatment was 54.08 years. Twenty patients had a previous surgical resection. The median prescribed dose was 12.32 Gy. Follow-up consisted of regular MRI, and audiological and neurological examination. RESULTS: Eighty percent of the patients completed a 10 year follow-up (range 0.63-16.32); imaging tests revealed that in 72.15% of them the tumor volume decreased by a mean of 46%, after an average time of 1.85 years (range 0.5-13.06), while in 15.18% stability was observed. Hearing loss, tinnitus and dizziness, previous most common symptoms (95%, 39% and 24% respectively), did not worsen significantly after treatment. Treatment failures as tumor growth progression, occurred in 10 patients at a mean of 53 months; salvage treatment was surgery in 7 and one patient was reirradiated. As for neuropathies, none of the18 patients with a previously affected facial nerve worsened, while 3 of 26 with trigeminal nerve dysfunction did. There have been no new neuropathies, radiographic abnormalities in brain stem, second tumors or tumoral malignant transformation. CONCLUSIONS: Our long-term results of GKRS in VS show a favorable neurological outcome, maintained excellent tumor growth control, without the development of secondary tumors or malignant transformation. We recommend a prolonged follow-up to better assess GKRS results in VS treatment.
X-Linked Wiskott–Aldrich Syndrome in a Girl
Authors: Ornella Parolini, Gabriele Ressmann, Oskar A. Haas, Johanna Pawlowsky, Helmut Gadner, Walter Knapp, Wolfgang Holter
Journal: New England Journal of Medicine (1998)

HE Wiskott-Aldrich syndrome is a life-threatening X-linked recessive disorder.Affected males present with recurrent infections, eczema, and thrombocytopenia with small platelets.The immune defect involves both humoral and cellular immunity and increases in severity with age. 1 The gene involved in this disease, located on the short arm of the X chromosome in the region Xp11.22-23, was recently cloned and named the Wiskott-Aldrich syndrome protein ( WASP ) gene. 2,3ifferent mutations or deletions within the WASP gene have been described in patients with the Wiskott-Aldrich syndrome and X-linked thrombocytopenia. 4The gene is expressed in early progenitor cells as well as in differentiated cells of various hematopoietic lineages. 5,6Evidence has been presented that WASP might be involved in cytoskeleton organization and signal transduction. 7][10] In contrast, in skin fibroblasts and cells from the buccal mucosa of female carriers there is random inactivation of the X chromosome. 8,102][13] When evaluated, the pattern of X-chromosome inactivation was found to be random, and the existence of an autosomal disorder that is clinically similar to classic Wiskott-Aldrich syndrome was postulated.We describe an eight-year-old girl with typical features of Wiskott-Aldrich syndrome.Molecular anal-
Abstract A16: Requirement of functionally active BRCA2 protein for the expression of IRF9-regulated genes in human breast cells
Authors: Mukul K. Mittal, Gautam Chaudhuri
Journal: Cancer Research (2009)

Abstract Interferons are cytokines that induces antiviral, immunomodulatory and antiproliferative effects to cells by inducing the expressions of many effector proteins. Type I interferons are often used to treat advanced stages of breast cancer. Unfortunately, in many cases interferon treatment does not produce any significant effect. We found that transient ablation of the breast cancer susceptibility gene BRCA2 in the human breast cells impairs the expressions of many type I interferon regulated genes. Thus, it appears that type I interferons need functional BRCA2 for their actions. We tested the promoter activity of several of the interferon target genes, such as GBP1, GBP2, ISG15, MX1, MX2, PKR etc. in the BRCA2 knocked-down human breast cells with or without added INF-alpha2a. The interferon-stimulated activity of the promoter decreased significantly in the BRCA2 knocked-down cells, further suggesting a possible role of BRCA2 in the interferon signal transduction pathway. Over expression of BRCA2 in the BRCA2-deficient pancreatic cancer cell Capan1 significantly increased the interferon-stimulated activity of the IFN-alpha-regulated gene promoters in these cells. We tested whether BRCA2 helps mediating the interferon pathway by interacting with the components of this pathway. The classical signal transduction pathway for the type I interferons involve the formation of the ternary complex ISGF3 among phosphorylated STAT1 and STAT2 with IRF9. Immuno-pull-down experiments revealed the binding of STAT1, STAT2 and IRF9 with BRCA2 in the human breast cells. Our study thus proposes a not-known-before role of the breast cancer susceptibility protein BRCA2 in the type I interferon pathway. Supported by the generous funding from US Department of Defense IDEA grant #W81XWH-08-1-0446 to GC. Citation Information: Cancer Res 2009;69(23 Suppl):A16.
Circulating tumor cells (CTC) predict progression free (PFS) and overall survival (OS) in patients with metastatic colorectal cancer
Authors: N. J. Meropol, S. J. Cohen, N. Iannotti, B. H. Saidman, K. D. Sabbath, M. C. Miller, G. V. Doyle, H. Tissing, L.W.M.M. Terstappen, C.J.A. Punt
Journal: Journal of Clinical Oncology (2007)

4010 Background: Treatment options for patients with metastatic colorectal cancer (mCRC) have recently expanded. However, the introduction of new regimens has highlighted the need for biomarkers to guide and monitor therapy. This study investigates the hypothesis that CTC levels can predict clinical outcomes in patients with mCRC. Methods: In a prospective multi-center study, 7.5 mL of blood from 456 patients with mCRC were tested for CTC using immunomagnetic separation before starting 1 st , 2 nd or 3 rd line therapy and at subsequent radiographic follow-up timepoints. Response on imaging was determined by participating centers. Results: Patients were stratified into unfavorable and favorable prognostic groups based on levels of =3 or &lt;3 CTC per 7.5mL, respectively. Median PFS, OS and significance between the two groups (log rank test) at different timepoints after the initiation of therapy is indicated in the table . The OS of patients converting to or maintaining unfavorable CTC at follow up timepoints was worse than for patients maintaining favorable CTC (12.6, 7.0 vs. 21.1 months, respectively, p&lt;0.0001). In multivariate analyses, which included age, ECOG performance status, and the line and type of therapy, CTC remained the most significant independent predictor of outcome. Conclusions: CTC levels before treatment and at subsequent timepoints are an independent predictor of PFS and OS in patients with mCRC. CTC levels of =3 per 7.5mL of blood after initiation of therapy are highly predictive of shorter PFS and OS. A large randomized phase III study to confirm these findings in mCRC patients receiving first line therapy recently completed accrual (DCCG CAIRO- 2). [Table: see text] No significant financial relationships to disclose.
P1116 BOCEPREVIR REAL-LIFE TREATMENT (BRIT) STUDY – PRACTICALITIES OF USING BOCEPREVIR-BASED TRIPLE THERAPY IN THE UNITED KINGDOM AND EARLY RESPONSES TO TREATMENT-WEEK 12 RESULTS
Authors: A. Mayes, A. Wilfin, N. Chamay, H. Tate, P. Robinson, H. Lamba
Journal: Journal of Hepatology (2014)
Prevention and Control of Pain in Children. A Manual for Health Care Professionals, by Royal College of Paediatrics and Child Health
Authors: J. McEniery
Journal: BMJ (1997)

Royal College of Paediatrics and Child Health BMJ Publishing Group, £15.95, pp 116 ISBN 0 7279 1178 3

The experiences of a wide group of contributors have been drawn upon for this publication, resulting in an intensely practical text about managing children's pain. This manual provides both a comprehensive overview and detailed advice on management. A strong theme of the book is our responsibility to infants and children to provide them with good control of their pain. Pain from procedures, surgery, trauma, and disease must be anticipated and assessed, especially for young infants and children for whom communication is limited. …
TEN–YEAR FOLLOW–UP OF THE DESIRE (DRUG–ELUTING STENTS IN THE REAL WORLD) REGISTRY
Authors: José de Ribamar Costa, Amanda Sousa, Adriana Moreira, Ricado Costa, Manuel Cano, Galo Maldonado, Cantidio Campos, None Neto, Enilto Egito, Ricardo Pavanelo, J Eduardo Sousa
Journal: Journal of the American College of Cardiology (2013)
Abstract P1-13-08: A Cross-Sectional Study Evaluating Bone Quantity and Quality in Women with Bone Metastases from Breast Cancer
Authors: OC Freedman, E Amir, AM Cheung, H Hu, E Lee, G Dranitsaris, MJ. Clemons
Journal: Cancer Research (2010)

Abstract Background: Approximately 1/3 of patients with metastatic breast cancer (MBC) and bone disease will sustain a skeletal related event (SRE) despite use of a bisphosphonate; there is therefore an urgent unmet need in this large population to better assess individual SRE risk and develop more effective bone protective agents. Using novel tools to assess bone quality may help guide individual patient treatment choices as well as future trial design. Materials and Methods: Women with MBC and bone metastases were recruited. Baseline bone assessments were performed using dual-energy X-ray absorptiometry (DXA) [areal bone mineral density (BMD) and vertebral fracture assessment (VFA)], high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum markers of bone turnover [serum CTX and bone-specific alkaline phosphatase (BAP)]. Risk factors for osteoporosis and fractures were then recorded. Results: 49 baseline assessments were completed. Mean age and body mass index were 53.6 (range 30-80) and 27 (range 17-45) respectively. One in four women had an ECOG 2-3, and 24% had a clinical fracture since the diagnosis of MBC. 94% had estrogen positive disease, 11% were HER2+. 53% had prior radiation therapy to bone; 90% received bisphosphonate therapy. Bone assessments are outlined in the Table. Vertebral compression deformity (VCD) using the novel technique of VFA was most strongly associated with clinical fracture (p = 0.003). Discussion: Prospective evaluation of individual SRE risk will enable improved patient-centred care and allow more rational use of bone targeted therapies. VFA is a novel tool that may better inform treatment decisions and choice of agents in women with MBC. Future follow-up of these patients will help determine the optimal assessment modality. Bone quantity and quality assessments Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-08.