tbuckley/cabot-search huggingface dataset:
A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab
Authors: Niels J. Sijbrandi, Eugen Merkul, Joey A. Muns, Dennis C.J. Waalboer, Kevin Adamzek, Marije Bolijn, Veronica Montserrat, Govert W. Somsen, Rob Haselberg, Paul J.G.M. Steverink, Hendrik-Jan Houthoff, Guus A.M.S. van Dongen
Journal: Cancer Research (2016)

Abstract Greater control is desirable in the stochastic conjugation technology used to synthesize antibody–drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable “semifinal” products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257–67. ©2016 AACR.
PTH-124 Regional ERCP Structure – Are We Able to Train Within A High Quality Service?
Authors: KA Mcwhirter, J McLaughlin, A Makin
Journal: Gut (2016)

<h3>Introduction</h3> ERCP services have traditionally developed dependent on local facilities and expertise. Recognising concerns regarding ERCP training and service provision, there have been efforts to describe the features of a high quality ERCP service and training program. Greater procedural volume leads to improved outcomes but there is no consensus on the effect this has on current ERCP service and training structure. We have reviewed how current regional practice fits into a suggested optimal service model and how training fits within this. <h3>Methods</h3> All ERCP endoscopists and trainees within the NorthWestern deanery were invited to complete an electronic survey of their routine practice. <h3>Results</h3> All 29 ERCP endoscopists, and 35 (79.5%) trainees, from 12 hospitals responded. All units fulfilled criteria for a high quality service with access to multidisciplinary meetings and interventional radiology facilities and audit protocol. However, there was no standard approach to assessment or management of common diagnoses. Half were confident that CBD stones &lt;10 mm would be removed in greater than 95% of occasions. Increased confidence was seen in higher volume operators. Pancreatitis prophylaxis (rectal NSAID or prophylactic pancreatic stenting) was not universally used, but more likely to be utilised by high volume operators. 7 of 9 units offering ERCP training provided training in the previous 12 months but there was no standardised approach, and no structure to allow exposure to higher case volume and complexity as training progressed. 54.2% of trainees declared an interest in ERCP training, with 37.1% currently training. All trainees had encountered difficulty obtaining training. 87.5% did not expect to be competent at CCT. <h3>Conclusion</h3> The current structure of this regional ERCP service fulfils suggested criteria for high quality service. This demonstrates that the current endoscopists are working with sufficient volume of cases to maintain expertise, and also have access to services to ensure appropriate and safe patient selection. However, there is no organisation of training. A high proportion of trainees are receiving limited training, and there is universal concern regarding availability. To optimise training within the region, we suggest that trainee numbers should be limited and a standardised training program developed. This would allow effective monitoring of training progression with the aim of producing a cohort of endoscopists who are near to or at a level of competence at the time of their CCT to start independent practice as a consultant or continue supervised practice as a post CCT fellow. <h3>Disclosure of Interest</h3> None Declared
Impact of Inherited Thrombophilia on Symptomatic Venous Thrombo-Embolism (VTE) in Children: A Systematic Review &amp; Meta-Analysis of 37 Studies Including 2470 Pediatric Patients.
Authors: Guy Young, Frauke Friedrichs, Anthony Chan, Gili Kenet, Paolo Simioni, Helen van Ommen, Anne Krumpel, Marianne Bonduel, Neil Goldenberg, Christophe Male, Manuela Albisetti, Marilyn Manco-Johnson, Leo Brandao, Ulrike Nowak-Gottl
Journal: Blood (2007)
AB0074 The Effect of Extracellular Vesicles on Human in Vitro Osteoclastogenesis in Health and in Arthritis
Authors: N. Marton, O.T. Kovacs, E. Baricza, D. Gyori, A. Mocsai, F. Meier, C.S. Goodyear, I.B. McInnes, E.I. Buzas, G.S. Nagy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Extracellular vesicles (EVs) like microvesicles (MVs) and exosomes (EXOs) are released in an evolutionary conserved manner by cells. EVs mediate intercellular communication with the transmission of molecules from their parent cell to their targets. <h3>Objectives</h3> Our objective was to investigate the effect of EVs on human <i>in vitro</i> osteoclastogenesis in healthy donors, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. <h3>Methods</h3> Blood samples of healthy volunteers, RA patients and PsA patients with peripheral arthritis were collected. EVs were isolated by filtration and differential centrifugation. CD14+ cells were isolated from PBMCs by using positive selection, and the cells were stimulated with 50 ng/ml recombinant human M-CSF for 24 hrs. Then the samples were treated with 50 ng/ml recombinant human RANKL and blood-derived microvesicles or exosomes. After 7 days, the cells were fixed and stained for tartarate resistant acid phosphatase (TRAP). TRAP-positive cells with at least 3 nuclei were considered as osteoclasts and counted by using the ImageJ software. <h3>Results</h3> Healthy and RA-derived exosomes significantly (p&lt;0.01) inhibited osteoclast differentiation of the CD14+ cells from the same donors, while PsA-derived exosomes had a stimulatory effect (p&lt;0.05) on osteoclastogenesis. In cross-induction experiments where EXOs and cells were interchanged between the 3 groups healthy (n=5) and RA (n=5) derived EXOs inhibited (p&lt;0.01) the generation of osteoclasts in both groups but PsA (n=7) derived EXOs did not have an inhibitory effect. Microvesicles did not alter the number of mature osteoclasts in any groups. <h3>Conclusions</h3> Our data suggest that EXOs profoundly regulate human osteoclastogenesis. PsA-derived EXOs stimulate, while healthy and RA-derived EXOs inhibit the osteoclast differentiation. <h3>Disclosure of Interest</h3> None declared
SAT0245 Comparison of Pain Characteristics in Patients with Rheumatoid Arthritis and Systemic Sclerosis: A Cross-Sectional Study:
Authors: G. Cengiz, K. Erol, K. Gok, S. Ozgocmen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by progressive destruction of inflamed joints leading to severe disability and functional loss. Systemic sclerosis is a multisystem autoimmune disease characterized by vasculopathy, diffuse fibrosis of skin and various internal organs. Pain is usually an overlooked entity in patients with SSc compared to RA. <h3>Objectives</h3> To compare pain characteristics particularly in terms of neuropathic pain (NeP) and to assess the possible impact of neuropathic component on functioning, physical and mental components of health related quality of life (HRQoL) in patients with RA and SSc. <h3>Methods</h3> Patients who met ACR/EULAR criteria for SSc and RA were recruited. Patients with prior diagnosis or taking medications for NeP, mood disorders, uncontrolled diabetes or neurological disorders or taking any biologic agents for their treatments were excluded. Patients were examined and evaluated for disease specific and generic outcome measures including disease activity parameters, physical functions, psychological status and health related quality of life measures (SF-36; HAQ; Hospital Anxiety and Depresson Scale, HADS). The DN4 interview and PainDetect questionnaire were applied by the same experienced physician who was blind to patients clinical and outcome data. Patients with a score ≥4 in DN4 were considered as “probable NeP”; between 13–18 or ≥19 in PainDetect were considered as “possible” or “likely NeP”, respectively. <h3>Results</h3> Fifty patients (44 F, 6 M) with SSc and fifty-one (45 F, 6 M) with RA were included. Patients had similar age and similar gender, educational and smoking status, as well as functioning and HRQoL. However, patients with RA declared more severe pain on VAS-pain (p=0.012), and higher body mass index than patients with SSc (p&lt;0.0001). NeP component was similar in patients with SSc vs RA. NeP component was detected 42.0% in SSc, and 47.1% in RA (p&gt;0.05) according to DN4 scores. According to PainDetect questionnaire, possible NeP was detected in 12.0% vs 15.7%, whereas 16.0% vs 17.6% had likely NeP in SSc and RA, respectively (p&gt;0.05). Neuropathic characteristics of pain were similar in SSc and RA defined as burning, electric shock, tingling, pins and needles, and itching except for numbness and painful cold which were significantly more prevalent in patients with SSc (%50.0 vs %25.5, p=0.011 and %50.0 vs %19.6, p=0.001; respectively). In SSc patients with or without NeP component had similar functioning and HRQoL measures. However, having NeP component revealed a heavier burden of disease regarding functioning, HRQoL and psychometric components patients with RA. <h3>Conclusions</h3> The NeP component was similar in patients with RA and SSc. However NeP was associated a heavier burden of disease in patients with RA. <h3>Disclosure of Interest</h3> None declared
Comparison of miRNA Profiles of Microdissected Hodgkin/Reed-Sternberg Cells and Hodgkin Cell Lines Versus CD77+ B-Cells Reveals a Distinct Subset of Differentially Expressed miRNAs
Authors: Bruce Poppe, Pieter Van Vlierberghe, Pieter Mestdagh, Tom Feys, An De Weer, Pascale De Paepe, Kathleen Lambein, Katleen De Preter, Nadine Van Roy, Jo Vandesompele, Bruno Verhasselt, Frank Speleman
Journal: Blood (2008)
AB0525 Correlation Analysis of Serum Cystatin C and Lipids Levels in Patients with Systemic Lupus Erythematosus
Authors: Z. Ye, Y. Zhang, X. Luo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To discuss the correlation between the level of serum cystatin C and lipids in patients with systemic lupus erythematosus. <h3>Methods</h3> Used automatic biochemical analyzer to detect serum cystatin C (CysC), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C) and hsCRP levels in 136 cases of SLE patients and 113 cases of healthy people. Data obtained using SPSS13.0 software to carry on statistical analysis. <h3>Results</h3> Outcome of SLE patients group comared with healthy controls, hsCRP (13.5±4.85 mg/L vs 2.03±0.88 mg/L), CysC (2.63±1.95 mg/L vs 0.85±0.37 mg/L), LDL-C (3.06±1.21 mmol/L vs 2.33±0.41 mmol/L), TC (5.32±2.63 mmol/L vs 4.02±1.67 mmol/L) and TG (1.92±0.83 mmol/L vs 1.44±0.8 mmol/L) were significantly different between the two groups. Compared with healthy controls, HDL-C (1.12±0.31 mmol/L vs 1.52±0.85 mmol/L) was decreased (P&lt;0.01). In SLE patients group, the serum CysC level and hsCRP, TC, TG and LDL-C were positively correlated, and the level of HDL-C was negative to the level of CysC. The health control group was no significant corretation. <h3>Conclusions</h3> Serum lipid levels of SLE patients were positive to the level of CysC. Suggest that joint detection of SLE patients serum CysC and blood lipids index is helpful to the diagnosis of SLE treatment and condition monitoring. <h3>References</h3> Ganda A, Magnusson M, Yvan-Charvet L. Mild renal dysfunction and metabolites tied to low HDL cholesterol are associated with monocytosis and atheroselerosis, Circulation, 2013,127(9):988–996 Doganer YC, Aydogan U, Aydogdu A, et al. Relationship of cystatin C with coronary artery disease and its severy. Coron Artery Dis, 2013,24(2):119–126 <h3>Disclosure of Interest</h3> None declared
AB0230 Centromere Pattern Exhibits A Specific Distribution of Titers among Anti-Nuclear Antibodies (ANAS) and Characterizes A Distinct Subset in Rheumatoid Arthritis
Authors: N. Kuramoto, C. Terao, K. Ohmura, K. Ikari, M. Furu, N. Yamakawa, K. Yano, M. Hashimoto, H. Ito, T. Fujii, K. Murakami, R. Sasai, Y. Imura, H. Yoshihuji, N. Yukawa, A. Taniguchi, S. Momohara, H. Yamanaka, F. Matsuda, T. Mimori
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> Centromere pattern is a staining pattern of anti-nuclear antibodies (ANAs). Here, we characterize the titer distribution of centromere pattern and analyze clinical and genetic features of centromere pattern-positive rheumatoid arthritis (RA). <h3>Methods</h3> We examined ANA by indirect immunofluorescence for 9,575 healthy volunteers and 1,211 RA patients without systemic sclerosis in Kyoto University Hospital. HLA-DRB1 was genotyped for 285 RA patients. We compared distributions of titers among ANA and analyzed associations between centromere pattern and clinical or genetic features in the subjects. For validation, we recruited another cohort of 2,424 RA patients in Tokyo Woman9s Medical University Hospital to confirm the associations between centromere pattern and clinical features. <h3>Results</h3> Eighty seven healthy volunteers (0.91%) and 25 RA patients (2.76%) were positive for centromere pattern of ANA. Centromere pattern was the only ANA staining pattern that demonstrated a definite bimodal distribution of levels in both healthy volunteers and patients with RA. Centromere pattern showed significantly higher levels than the other ANA patterns in the subjects positive for each ANA (p&lt;0.0001). Centromere pattern-positivity was associated with old age and females in both healthy population and patients with RA. Centromere pattern-positive patients with RA showed lower positivity of rheumatoid factor (RF) (p=0.0011) that is one of risk factors for bone destruction. Centromere pattern was associated with Raynaud9s phenomenon and complication of Sjögren9s syndrome and primary biliary cirrhosis (p≤0.0052). No HLA-DRB1 alleles were significantly associated with centromere pattern. In validation study, 82 RA patients (2.41%) were positive for centromere pattern. Centromere pattern-positivity was again associated with old age, females and negativity of RF (p≤0.0044). Information of complications and symptoms was not available in the replication cohort. Centromere pattern-positive patients tended to show higher Total Sharp Score in spite of lower frequencies of RF in both cohorts. <h3>Conclusions</h3> Centromere pattern showed a specific distribution of levels among ANA. Centromere pattern-positive RA is a distinct subset with specific clinical features and complications. Centromere pattern is a possibly new risk factor of bone destruction in RA. <h3>Disclosure of Interest</h3> None declared
Immunodeficiency Associated with a STAT-5b Mutation and Growth Hormone Insensitivity.
Authors: Aileen M. Cleary, Vivian Hwa, Wenwei Tu, Kira Dionis, Liliana Bezrodnik, Alejandro Teper, Maria Gaillard, Juan J. Heinrich, Ron G. Rosenfeld, David B. Lewis
Journal: Blood (2004)
High Density SNP Arrays Reveal That Distinct Clonal Lesions Including Uniparental Disomy Can Be Detected in a Proportion of Patients with Aplastic Anemia with Normal Metaphase Cytogenetics.
Authors: Marcin Wlodarski, Christine O’Keefe, Lukasz Gondek, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2006)
Myelodysplastic Syndromes in Adults - Preliminary Results From the First, Retrospective, Multicenter Brazilian Registry.
Authors: Silvia M.M. Magalhães, Rosane Bittencourt, Elvira Velloso, Maria de Lourdes Chauffaille, Alita Andrade Azevedo, Evandro M. Fagundes, Maria Aparecida Zanichelli, Gloria Bonfim, Ligia Niero Melo, Tereza Cristina Bortolheiro, José Wellington Oliveira Lima
Journal: Blood (2009)
AB0483 Risk Factors Associated with Greater Damage in Systemic Lupus Erythematosus Patients: An Egyptian Multicenter Study
Authors: M. Eissa, M. Hammad, S. Fathi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disorder. The total damage in a patient with SLE may result from SLE itself or any other pathologic process. The management of SLE targets immediate control of disease activity, but also it should include the prevention of organ damage from treatment and comorbidity by minimizing or controlling risk factors of organ damage. <h3>Objectives</h3> The aim of this study was to assess risk factors of greater damage in a sample of Egyptian SLE patients. <h3>Methods</h3> This is an Egyptian multicenter retrospective study. The study included 100 SLE patients: 64 patients from Cairo University Hospital and 36 patients from Zagazig University Hospital. The patients are classified according to the Systemic Lupus International Collaborative Clinics (SLICC) criteria for SLE. Systemic Lupus International Collaborative Clinics/ACR Damage Index (SLICC/ACR-DI) was used to measure damage in each patient. The period of data collection took 4 months. The collected data included demographic, clinical, serologic data and medications. <h3>Results</h3> 100 SLE patients (93% females and 7% males with mean age 33.44±8.6 and disease duration 6.25 (1–17) were included. The most frequent item in the damage index in our patients was retinal changes or optic atrophy (12%), followed by osteoporosis (11%). The total SLICC/ACR Damage Index Score ranged from 0 to 8. There was a significant positive correlation between the Damage Index and the patient9s age, SLEDAI-2k at the onset and at the last visit (P&lt;0.05). A higher Damage Index score was found in hypertensive patients compared to normotensive patients and among those with positive anti-phospholipid antibodies compared to those with negative anti-phospholipid antibodies and the difference was statistically significant (P&lt;0.01). A statistically significant higher Damage Index score was found in cyclophosphamide users compared to non-users, and in those with proteinuria &amp; seizures compared to those without (P&lt;0.05). Comparing all variables; seizures was by far the most important predictor of Damage Index in the regression model (Beta=0.279, P=0.028), followed by SLEDAI at last visit (Beta =0.234, P=0.062) and then Antiphospholipid Syndrome (Beta =0.335, P=0.064). <h3>Conclusions</h3> Damage in SLE cannot be prevented completely as SLE is an aggressive disease treated by aggressive medications. Frequent ophthalmologic follow up is necessary for all SLE patients. SLE patients with hypertension and positive antiphospholipid antibodies develop higher damage scores so they need closer observation and control of these factors if possible. Rheumatologists should try to minimize damage as much as possible to maintain patients9 health, functioning, and general wellbeing. <h3>Disclosure of Interest</h3> None declared
Human Interleukin-3/Granulocyte Macrophage-Colony Stimulating Factor Knock-In Mice Support Human Myeloid Cell Reconstitution and Human Immune Responses In the Lung.
Authors: Tim Willinger, Anthony Rongvaux, Hitoshi Takizawa, Elizabeth E. Eynon, Sean Stevens, Markus G Manz, Richard A. Flavell
Journal: Blood (2010)
Bortezomib, Intravenous Cyclophosphamide and Dexamethasone (VelCD) for Previously Untreated Multiple Myeloma: An Interim Analysis of the German DSMM XIa Trial
Authors: Stefan Knop, Peter Liebisch, Hannes Wandt, Martin Kropff, Volker Kunzmann, Katja Weisel, Daniel Franke, Monika Engelhardt, Lorenz H. Truemper, Nikolaus Kroeger, Burkhard Hennemann, Michael Pfreundschuh, Martin Gramatzki, Bernd Metzner, Christian Peschel, Herbert G. Sayer, Orhan Sezer, Heinz A Duerk, Bernd Hertenstein, Hans-Guenther Mergenthaler, Hella Gollasch, Hans-Heinrich Wolf, Georgia Schilling, Claas Frohn, Hermann Einsele
Journal: Blood (2008)
Expression of γ-Globin Is Reactivated by a Novel Mechanism in Baboon CD34+ Erythroid Progenitor Cell Cultures.
Authors: Donald Lavelle, Janet Chin, Mahipal Singh, Kestis Vaitkus, Virryan Banzon, Tatiana Kousnetzova, Maria Hankewych, Joseph DeSimone
Journal: Blood (2007)
Clinical Relevance of Vascular Endothelial Growth Factor Type A (VEGFA) and VEGF Receptor Type 2 (VEGFR2) Gene Polymorphism In Chronic Lymphocytic Leukemia
Authors: Joanna Gora-Tybor, Krzysztof Jamroziak, Zofia Szemraj, Janusz Szemraj, Ewa Lech-Maranda, Olga Grzybowska-Izydorczyk, Katarzyna Oszajca, Krzysztof Giannopoulos, Tadeusz Robak
Journal: Blood (2010)
Targeting the CD28-B7 Pro-Survival Pathway In Multiple Myeloma
Authors: Jayakumar Nair, Louise Carlson, Cheryl H Rozanski, Chandana Koorella, Megan Murray, John Shaughnessy, P.Leif Bergsagel, Lawrence H. Boise, Asher A. Chanan-Khan, Kelvin P Lee
Journal: Blood (2010)
Pre-Transplant Variables Affecting the Outcome of Submyeloablative Allogeneic HSCT in Uniformly Treated Patients with Hematologic Malignancies.
Authors: Jayesh Mehta, S. Singhal, M. Tallman, S. Williams, J. Winter, A. Evens, D. Grinblatt, L. Kaminer, L. Gordon
Journal: Blood (2004)
Usefulness of Eltrombopag in Secondary ITP Patients in Clinical Practice
Authors: Tomás José González-López, María Teresa Alvarez-Roman, Cristina Pascual, Blanca Sánchez-González, Fernando Fernández-Fuentes, Gloria Pérez-Rus, José Angel Hernández-Rivas, Silvia Bernat, Montserrat Cortés, José María Bastida, Violeta Martínez-Robles, Angeles Fernández-Rodríguez, Pavel Olivera, Estefanía Bolaños, Rafael Alonso, Laura Entrena, Marta Gómez-Nuñez, Nuria Bermejo, María Paz Martínez-Badas, María Jesús Peñarrubia, Arancha Alonso, Inmaculada Soto, María Yera Cobo, Alberto Casaus, Isabel Caparrós, María Perera, Reyes Jiménez Bárcenas, Cecilia Heras, María Calbacho, Maria Tenorio, Armando Luaña, Elsa Lopez-Ansoar, Gerardo Hermida, Javier García-Frade, José Ramón González-Porras, Miguel A. Sanz
Journal: Blood (2015)
Incidence and Prognostic Value of TP53 Mutations in Lower Risk MDS with Del 5q.
Authors: Cecile Bally, Lionel Ades, Aline Renneville, Sophie Raynaud, Virginie Eclache, Thomas Cluzeau, Mathilde Hunault-Berger, Aspasia Stamatoullas, Christian Bastard, Michaela Fontenay, Marie-Joelle Mozziconacci, Claude Preudhomme, Hugues de The, Pierre Fenaux, Jacqueline Lehmann-Che
Journal: Blood (2012)
Array CGH Analysis for Target Genes at 6p21 Amplification Region in Diffuse Large B-Cell Lymphoma.
Authors: Yumiko Kasugai, Hiroyuki Tagawa, Yoshihiro Kameoka, Sivasundaram Karnan, Ritsuro Suzuki, Shinobu Tsuzuki, Yoshitaka Hosokawa, Masao Seto
Journal: Blood (2004)
Comprehensive Hybrid Capture-Based Genomic Profiling of T-Cell Leukemias and Lymphomas Reveals Targetable JAK1 and JAK3 Co-Existing Mutations
Authors: Utpal P. Dave, Norma Palma, Kai Wang, Nishitha M Reddy, Siraj Ali, Rati Tripathi, Allison Greenplate, Jonathan Michael Irish, Derya Unutmaz, Phil J Stephens, Vincent A. Miller
Journal: Blood (2014)