tbuckley/cabot-search huggingface dataset:
PTH-099 Probing The EGFR (Epidermal Growth Factor Receptor) Signalling Pathway in Colorectal Liver Metastases (CRLM)
Authors: JE Barrett, PN Siriwardana, S Singh, P Kim, D Hochhauser, BR Davidson, T Ng
Journal: Gut (2016)

<h3>Introduction</h3> Overexpression and activation of the components of the EGFR/ErbB pathway has a prognostic significance in CRLM. HER2 (ErbB2) and HER3 (ErbB3) have previously been found to be overexpressed in CRLM with ErbB3 overexpression being associated with good prognosis. The ErbB signalling pathway consists of multiple molecular components. These components interact in a complex non-linear manner which makes it challenging to understand how the system functions. For example, the dimerization between ErbB receptors plays a crucial role in downstream signalling activation. Mathematical modelling can help to quantify network properties and understand its behaviour under various conditions. Birtwistle (2007) developed a mathematical model of the EGFR signalling pathway which focused on early pathway response to stimulation of the ErbB receptors. Using this model, we aimed to understand how the ErbB pathway functions in CLRM. <h3>Methods</h3> Lysates of fresh frozen CRLM samples from 18 patients who were chemonaive for CLRM were analysed using a proteomics-based assay Collaborative Enzyme Enhanced Reactive immunoassay (CEER) to quantify the phosphorylated and non-phosphorylated forms of ErbB family receptors and phosphorylated downstream ErbB pathway factors. We used a model of the EGFR signalling pathway previously developed by Birtwistle (2007) and validated using data from a breast cancer cell line to try and reproduce the activation patterns of HER1, HER2, and HER3. <h3>Results</h3> CRLM with high levels of both HER2 and HER3 were associated with high levels of phosphorylated HER3 (pHER3) and vice versa (p &lt; 0.001). A similar relationship was observed between pHER3 and HER1, HER2 (p &lt; 0.0001); and HER1, cMET (p = 0.006). Simulations focused on pHER3 for high and low levels of HER1, HER2, and HER3. The simulated relationship between pHER3 and HER1, HER2 was in good agreement with our observed data. High and low levels of both HER1, HER2 and HER1, HER3 also showed good agreement. Some discrepancy between simulation and experiment was found for high values of HER1 and low values of HER2 (and vice versa). <h3>Conclusion</h3> Simulations were performed to understand the dynamics of the EGFR pathway and showed partial agreement between the Birtwistle model and CEER data.The Birtwistle model which was designed to only capture the early network response to stimulation of ErbB receptors in breast cancer cells may not be directly applicable to resected CRLM. Further refinement of the model is required in the future. <h3>Disclosure of Interest</h3> None Declared
Upregulation of Lipid Metabolism Modulators in Myeloma Cells Underlines Their Progression in a Supportive Microenvironment and Linking Metabolic Pathways with Growth Signaling
Authors: Sathisha Upparahallivenkateshaiah, Khan Sharmin, Ling Wen, Rakesh Bam, Xin Li, Shmuel Yaccoby
Journal: Blood (2012)
Nonmyeloablative Unrelated Donor Hematopoietic Cell Transplantation (HCT) for Patients (pts) with Poor Risk, Relapsed or Refractory Multiple Myeloma.
Authors: George E. Georges, Michael B. Maris, Brenda M. Sandmaier, Judith Shizuru, Dietger W. Niederwieser, Edward Agura, Benedetto Bruno, Peter A. McSweeney8, Rainer F. Storb, David G. Maloney
Journal: Blood (2004)
Pharmacologic Inhibition with Duvelisib (IPI-145) and Genetic Inhibition of PI3K p110δ Antagonizes Intrinsic and Extrinsic Survival Signals in Chronic Lymphocytic Leukemia (CLL)
Authors: Shuai Dong, Daphne Guinn, Jason A Dubovsky, Yiming Zhong, Amy Lehman, Jeff Kutok, Jennifer A. Woyach, John C. Byrd, Amy J. Johnson
Journal: Blood (2014)
RNAi-Mediated Inhibition of Tmprss6 Ameliorates Anemia and Secondary Iron Overload in a Mouse Model of β-Thalassemia Intermedia and Decreases Iron Overload in Hfe−/− Mice
Authors: Paul J Schmidt, Anoop K Sendamarai, Ivanka Toudjarska, Tim Racie, Jim S Butler, Mark D. Fleming, David Bumcrot
Journal: Blood (2012)
PWE-058 The Role of A Point of Care Test, Simtomax, in Predicting Histological Remission in Coeliac Disease on A Gluten Free Diet: Abstract PWE-058 Table 1
Authors: MS Lau, PD Mooney, WL White, M Burden, SH Wong, M Kurien, DS Sanders
Journal: Gut (2016)

<h3>Introduction</h3> Coeliac disease (CD) is a chronic inflammatory enteropathy treated with a gluten free diet (GFD). Clinical symptoms and complications of CD are thought to be associated with ongoing duodenal inflammation due to continued gluten exposure, hence the optimal assessment of response to a GFD is histological remission. However, there is little consensus in the UK on routine re-biopsy during follow up. Duodenal biopsy requires a gastroscopy which is invasive and can be poorly tolerated. Coeliac serology and dietetic evaluation have been used as surrogate markers for histological remission, but the correlation has been shown to be poor. We aimed to assess the role of an IgA/G-deamidated gliadin peptide (DGP) based point of care test (POCT), Simtomax, in predicting histological remission in CD. <h3>Methods</h3> We prospectively recruited patients with known CD attending for a gastroscopy with duodenal biopsy for the assessment of disease remission. All patients underwent a blood test for IgA-endomysial antibodies (EMA), IgA-tissue transglutaminase antibodies (TTG), total IgA levels and Simtomax at the point of endoscopy. They also completed a validated GFD adherence questionnaire (Biagi) which gives a 5 point score (0–4), with the highest score indicating strict adherence to a GFD. Patients with an adherence score of 3 or 4 were considered to follow a strict GFD. A gastroscopy was then performed with quadrantic biopsies taken from the second part of the duodenum and one biopsy taken from the duodenal bulb. We compared all surrogate markers to the gold standard of duodenal histology. <h3>Results</h3> 145 (74% female, median age 53) patients with CD on a GFD were recruited from 2013–2015. 52 (36%) patients had persistent villous atrophy. Simtomax was the most sensitive in predicting villous atrophy (78.8%). The sensitivities of EMA, TTG and the GFD adherence score were significantly lower than that of Simtomax. Simtomax had the best negative predictive value (NPV) for villous atrophy at 82.5%. <h3>Conclusion</h3> Simtomax exceeds all other available surrogate markers in predicting the presence of villous atrophy. Simtomax could be used to aid informed decision making in patients who require but are reluctant to undertake a gastroscopy for duodenal biopsy to assess for disease remission. It could also act as a useful adjunct to identify patients who may require further dietetic support. <h3>Disclosure of Interest</h3> M. Lau: None Declared, P. Mooney: None Declared, W. White: None Declared, M. Burden: None Declared, S. Wong: None Declared, M. Kurien: None Declared, D. Sanders Grant/research support from: Tillotts Pharma for investigator led studies in coeliac disease. None of the funding sources had any input in the study design, access to study data, interpretation of the findings or drafting of the abstract.
Non-Total Body Irradiation (TBI) Containing Preparative Regimen in Alternative Donor Bone Marrow Transplantation (BMT) for Severe Aplastic Anemia (SAA).
Authors: Je-Hwan Lee, Seong-Jun Choi, Jung-Hee Lee, Young-Shin Lee, Miee Seol, Jung-Shin Lee, M. Wookun Kim, Kyoo Hyung Lee
Journal: Blood (2004)
Panobinostat Plus Azacitidine in Adult Patients with MDS, CMML, or AML: Results of a Phase 2b Study
Authors: Guillermo Garcia-Manero, Mikkael A. Sekeres, Miklos Egyed, Giuliana Alimena, Carlos Graux, Jamie D. Cavenagh, Huda Salman, Arpad Illes, Pierre Fenaux, Daniel J. DeAngelo, Reinhard Stauder, Karen Yee, Nancy Y Zhu, Je-Hwan Lee, David Valcarcel, Alan MacWhannell, Zita Borbenyi, Antje Wegener, Lucien Gazi, Suddhasatta Acharyya, Florence Binlich, Oliver G. Ottmann
Journal: Blood (2015)
PTU-036 Safety of Radiofrequency Ablation Following Endoscopic Resection in Barrett’s Neoplasia: Does Resection Method Matter?: Abstract PTU-036 Table 1
Authors: S Subramaniam, F Chedgy, K Kandiah, S Thayalasekaran, P Bhandari
Journal: Gut (2016)

<h3>Introduction</h3> The current standard of treating Barrett’s neoplasia is resection of visible lesions followed by ablative therapy to the Barrett’s segment. Endoscopic mucosal resection (EMR) is the conventional method of resection although there is growing evidence for the use of endoscopic submucosal dissection (ESD). Radiofrequency ablation (RFA) is a safe and effective ablation technique but carries a risk of complications including bleeding, stricture and perforation. ESD is associated with much deeper submucosal dissection then EMR, resulting in a deeper and thicker scar. This has been a cause for concern whilst performing RFA after ESD and experts have raised the possibility of higher stricture or perforation rates with RFA after ESD. We wish to compare the safety and efficacy of radiofrequency ablation following EMR and ESD and to ascertain if there are any significant differences. <h3>Methods</h3> An electronic database (from 2007–2015) of all patients who had endoscopic resections (EMR or ESD) for Barrett’s neoplasia followed by RFA was analysed. Data was collected on patient demographics, Barrett’s length, lesion size, number of ablations required and follow up period. The clearance of neoplasia (high grade dysplasia/intramucosal cancer) was also recorded (CE-N) along with procedural complications including bleeding, perforation and strictures. <h3>Results</h3> There were 30 patients in the EMR + RFA group (average age 73.1 years) compared to 19 in the ESD + RFA group (average age 74.6 years). Patients received circumferential ablation (HALO 360) or focal ablation (HALO 90/60/Ultra) depending on the extent of residual Barrett’s oesophagus post endoscopic resection. The table below shows the outcome of RFA following EMR or ESD. ESD was started in our institution later than EMR and that is reflected in lower numbers and shorter follow up in the ESD cohort but it is otherwise a well matched population. <h3>Conclusion</h3> This is the first UK series reporting on the safety and efficacy of RFA after ESD. RFA following ESD or EMR is equally safe and effective and the endoscopic resection method is not a significant factor when planning ablation therapy. <h3>Disclosure of Interest</h3> None Declared
Hierarchical Evaluation of Baseline Poor-Prognosis Factors and Response to Initial Therapy in Younger Adults with Ph-Negative Acute Lymphoblastic Leukemia (ALL) Treated in the Risk-Adapted GRAALL-2003 Study.
Authors: Francoise Huguet, Arnaud Pigneux, Eric Delabesse, Xavier Thomas, Kheira Beldjord, Martine Escoffre, Jean-Luc Harousseau, Oumedaly Reman, Frederic Garban, Agnes Buzyn, Marina Lafage, Yves Chalandon, Andre Delannoy, Jean-Paul Vernant, Veronique Lheritier, Marie-Christine Bene, Norbert Ifrah, Elizabeth MacIntyre, Herve Dombret
Journal: Blood (2005)
Group membership: Who gets to decide?
Authors: Anne Jaap Jacobson
Journal: Behavioral and Brain Sciences (2016)

Abstract In this commentary, I focus on several problems that the authors' understanding of group identity raises: the legality of avoiding background diversity, the problem of effectively unshareable knowledge, the practical quality of some outcomes arrived at by groups with homogeneous backgrounds, and moral issues about fairness. I note also that much recent research challenges the view that background diversity is more likely to be a detriment than a benefit.
Donor Lymphocyte Infusion for Mixed Chimerism or Residual Disease after Reduced-Intensity T Cell Depleted Stem Cell Transplantation Results in Conversion to Full Donor Chimerism Combined with Graft Versus Tumor Responses and Limited GVHD.
Authors: Peter A. von dem Borne, Ingrid Starrenburg, Erik W.A. Marijt, Stijn Halkes, J.H. Frederik Falkenburg, Roel Willemze
Journal: Blood (2007)
Production and Characterization of Novel Neutralizing mAbs Against vWF-A3 Domain, an Inhibitor of Binding of vWF to Collagen and Influence of Interaction between vWF and Platelet GPIbα.
Authors: Yiming Zhao, Ningzheng Dong, Liqian Xie, Fei Sheng, Changgeng Ruan
Journal: Blood (2006)
AB0185 Undercarboxylated Osteocalcin as A Marker for Metabolic Dysfunction in Patients with Rheumatoid Arthritis
Authors: E.-J. Lee, B. Ghang, D.-H. Lim, S. Hong, C.-K. Lee, B. Yoo, Y.-G. Kim
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Osteocalcin (OC) has been known as one of bone-forming markers and the serum level in rheumatoid arthritis (RA) patients was usually lower than that in healthy control. Serum OC, secreted from osteoblasts, exists in either carboxylated OC (cOC, major form) or undercarboxylated OC (ucOC, minor form). Different to the osteogenic role of cOC, ucOC has been suggested to be involved in energy metabolism. Recent studies have shown that significantly lower concentration of ucOC in the blood was associated with metabolic derangement including insulin resistance. Therefore, we would like to investigate whether level of ucOC in RA patients decreased and it was accompanied by metabolic dysregulation, which has never been studied before. <h3>Objectives</h3> To determine the association between ucOC and metabolic alteration including insulin resistance in patients with RA <h3>Methods</h3> Clinical information of patients and healthy volunteers was collected from electronic data base of single center registry. The concentrations of cOC and ucOC were measured in the sera from established RA patients (n=30) and healthy subjects (n=13) by enzyme-linked immunosorbent assay (ELISA). Various metabolic parameters, including insulin concentration, homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index (BMI), were measured and analyzed. <h3>Results</h3> The concentration of cOC in blood was not significantly different between RA patients (13.49±2.97 ng/mL) and healthy controls (14.45±2.48 ng/mL). However, the concentration of ucOC was significantly lower in the sera of patients with RA (3.29±2.36 ng/mL) than in those of healthy individuals (5.94±2.75 ng/mL, <i>p</i>=0.003). Intriguingly, ucOC levels have been found to be positively associated with parameters of metabolic derangement including insulin levels, HOMA-IR and BMI (Figure 1). These associations were not found in healthy controls. <h3>Conclusions</h3> The present study show that the concentration of ucOC, but not cOC was significantly lower in patients with RA, and its value was positively correlated with insulin resistance. Therefore, ucOC can be supposed to have a unique role in metabolic dysregulation in RA. <h3>Disclosure of Interest</h3> None declared
P147 Effect of cannabis smoking on respiratory symptoms and lung function: a structured literature review
Authors: L Ribeiro, P Ind
Journal: Thorax (2016)

<h3>Background</h3> With increasing cannabis use, physicians need to know more about its respiratory effects. However, there are few long term studies of cannabis smoking, due to legality issues and confounding effects of tobacco. <h3>Aims</h3> We reviewed effect of chronic cannabis use on respiratory symptoms and lung function, particularly FEV1, FVC and FEV1/FVC ratio. <h3>Methods</h3> 19 out of 256 English-language publications, prior to June 2015, from MEDLINE, Scopus, and Web of Science databases, reporting lung function in chronic cannabis users, were examined. <h3>Results</h3> 11 cross-sectional studies and 8 observational cohort studies were included. All 9 studies (n = 11,848) examining respiratory symptoms reported an increase with cannabis smoking (odds ratio up to 3.0). 2 studies (n = 1,336) reported that quitting cannabis with/without tobacco reduced chronic bronchitis symptoms to those of never cannabis smokers. 8 studies (n = 9,939) reported no significant changes in FEV1/FVC; 6 (n = 3,722) found a significant decrease (0.5%−1.9%) in chronic marijuana only smokers compared to controls. While most reports omitted absolute FVC results, 3 large studies (n = 13,858) demonstrated increased FVC with marijuana smoking. 4 studies (n = 13, 674) found dose-related reductions in FEV1/FVC. 7 studies associated chronic cannabis smoking with other evidence of airflow obstruction [increased airway resistance in 3; (0.03 to 0.38 cm H<sub>2</sub>O/L/s), reduced specific airway conductance in 4; (0.007 to 0.07 mL/s/cm H<sub>2</sub>O/L)]. The larger studies (n = 13,858) suggested increased FVC may cause reduced FEV1/FVC chronically.<sup>1</sup> This contrasts with airflow obstruction in tobacco smoking. Anti-inflammatory or acute bronchodilator effects of cannabis, on top of chronic effects, may partly explain these results. <h3>Conclusions</h3> Cannabis, like tobacco, smoking causes chronic bronchitis but increased FVC is more consistently found than reduced FEV1. No studies in marijuana smokers have found a linear decline in FEV1 with time. More work is needed to explain the differing effects on lung function and to examine effects on small airways, imaging and histology. <h3>Reference</h3> Hancox RJ, <i>et al</i>. Effect of cannabis smoking on lung function: a population-based cohort study. <i>Eur Respir J</i> 2010;<b>35</b>:42–7.
Impact of Cytogenetic and Molecular Markers on Disease-Free Survival of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia
Authors: Yue Lu, Tong Wu, Xing-Yu Cao, Yan-Li Zhao, De-Yan Liu, Min Xiong, Jian-Ping Zhang, Rui-Juan Sun, Zhi-Jie Wei, Jia-Rui Zhou, Hong-Xing Liu, Tong Wang, Shu-Quan Ji, Dao-Pei Lu
Journal: Blood (2015)
PWE-140 Relationship Between Social Deprivation and The Care Pathway of Osoephago-Gastric (OG) Cancer Patients
Authors: M Varagunam, D Cromwell
Journal: Gut (2016)

<h3>Introduction</h3> Incidence and mortality of all cancers combined in England are higher in individuals living within the most deprived areas compared to those from the least deprived. The government recognises that overall performance can be improved for people living in deprived areas. We analysed the effect of deprivation on the care pathway of patients with OG cancer. <h3>Methods</h3> This study used data collected by the National Oesophago-Gastric Cancer audit (NOGCA) between April 2012 and March 2014 to evaluate the effect of social deprivation on the route of referral into secondary care and treatment options. Social deprivation was measured using the English Index of Multiple Deprivation, with patients allocated to quintiles based on the deprivation score for their area of residence. Quintile 1 represents the least deprived group and quintile 5 the most deprived. Analysis was performed using multivariable logistic regression. <h3>Results</h3> 16,635 patients were included in the study with a mean age of 70.4 years and 69.2% males. The proportion of patients who were diagnosed after an emergency admission was 11.4% in the least deprived group and 16.4% in the most deprived group. An increase in a quintile of deprivation was associated with an 18% increase in risk of an emergency admission after adjusting for risk factors (age at diagnosis, sex, pre-treatment TNM stage, co-morbidities, site of tumour, and performance status), odds ratio (CI) 1.18 (1.1,13) p = 0.001. With every increase in the quintile of deprivation, there was a 8% decrease in likelihood of having curative surgery, odds ratio (CI) 0.92 (0.90,0.96) p &lt; 0.001 after adjusting for route of referral and risk factors . <h3>Conclusion</h3> The treatment pathway of patients with OG cancer differs among patients living in different areas of social deprivation, with most deprived patients being more likely to be diagnosed after an emergency admission and less likely to have curative surgery. The reasons for the variation needs to be investigated to improve overall outcomes. <h3>Disclosure of Interest</h3> None Declared
Nivolumab in the Treatment of Hodgkin Lymphoma
Authors: Stephen M. Ansell
Journal: Clinical Cancer Research (2016)

Abstract Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed–Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed–Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein–Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDA for patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma. Clin Cancer Res; 23(7); 1623–6. ©2016 AACR.
Identification of CKMT1B As a New Target in EVI1-Positive AML
Authors: Alexandre Puissant, Nina Fenouille, Christopher F. Bassil, Issam Ben-Sahra, Gabriela Alexe, Lina Benajiba, Azucena Ramos, Yana Pikman, Michael R. Burgess, Ilene Galinsky, Daniel J. DeAngelo, Richard M. Stone, Kevin Shannon, Michael T. Hemann, Kimberly Stegmaier
Journal: Blood (2015)