tbuckley/cabot-search huggingface dataset:
Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining T <sub>reg</sub> and antitumor CTL function
Authors: Brian C. Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L. Cubitt, Steven Gunawan, Harshani R. Lawrence, Nicholas J. Lawrence, Said M. Sebti, Claudio Anasetti
Journal: Science Translational Medicine (2017)

Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs). Aurora A/JAK2 inhibition is immunosuppressive but permits the differentiation of inducible regulatory T cells (iTregs) that are hyperfunctional and CD39 bright and efficiently scavenge adenosine triphosphate (ATP). Increased iTreg potency is primarily a function of Aurora A blockade, whereas JAK2 inhibition suppresses T helper 17 (TH17) differentiation. Inhibiting either Aurora A or JAK2 significantly suppresses TH1 T cells. However, CTL generated in vivo retains tumor-specific killing despite Aurora A/JAK2 blockade. Thus, inhibiting CD28 and IL-6 signal transduction pathways in donor T cells can increase the Treg/Tconv ratio, prevent GVHD, and preserve antitumor CTL.
Quaternary Organization of GPIb-IX Complex and Insights Into Bernard-Soulier Syndrome Revealed by the Crystal Structures of GPIbβ Ectodomain and a GPIbβ/GPIX Chimera
Authors: Paul A. McEwan, Wenjun Yang, Katherine H. Carr, Xi Mo, Xiaofeng Zheng, Renhao Li, Jonas Emsley
Journal: Blood (2011)
Microrna Expression in Fludarabine-Refractory CLL Implicates Independent Mechanisms of Resistance and Is Associated with Response and Progression Free Survival After Alemtuzumab Treatment: Results From the CLL2H Trial.
Authors: Johannes Bloehdorn, Martin Sill, Andreas Bühler, Silja Mack, Doris Winter, Lars Bullinger, Arefeh Rouhi, Florian Kuchenbauer, Daniel Mertens, Axel Benner, Michael Hallek, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2012)
Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation
Authors: Elizabeth A. Jacobsen, Sergei I. Ochkur, Alfred D. Doyle, William E. LeSuer, Wen Li, Cheryl A. Protheroe, Dana Colbert, Katie R. Zellner, HuaHao H. Shen, Charles G. Irvin, James J. Lee, Nancy A. Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The release of eosinophil granule proteins in the lungs of patients with asthma has been dogmatically linked with lung remodeling and airway hyperresponsiveness. However, the demonstrated inability of established mouse models to display the eosinophil degranulation occurring in human subjects has prevented a definitive in vivo test of this hypothesis.To demonstrate in vivo causative links between induced pulmonary histopathologies/lung dysfunction and eosinophil degranulation.A transgenic mouse model of chronic T-helper cell type 2-driven inflammation overexpressing IL-5 from T cells and human eotaxin 2 in the lung (I5/hE2) was used to test the hypothesis that chronic histopathologies and the development of airway hyperresponsiveness occur as a consequence of extensive eosinophil degranulation in the lung parenchyma.Studies targeting specific inflammatory pathways in I5/hE2 mice surprisingly showed that eosinophil-dependent immunoregulative events and not the release of individual secondary granule proteins are the central contributors to T-helper cell type 2-induced pulmonary remodeling and lung dysfunction. Specifically, our studies highlighted a significant role for eosinophil-dependent IL-13 expression. In contrast, extensive degranulation leading to the release of major basic protein-1 or eosinophil peroxidase was not causatively linked to many of the induced pulmonary histopathologies. However, these studies did define a previously unappreciated link between the release of eosinophil peroxidase (but not major basic protein-1) and observed levels of induced airway mucin.These data suggest that improvements observed in patients with asthma responding to therapeutic strategies ablating eosinophils may occur as a consequence of targeting immunoregulatory mechanisms and not by simply eliminating the destructive activities of these purportedly end-stage effector cells.
LS104, a Novel Kinase Inhibitor, Induces Apoptosis, Synergizes with Cytostatic Drugs and Is Targeting the Receptor Tyrosine Kinase FLT3.
Authors: Stefan Kasper, Thomas Kindler, Florian Heidel, Frank Breitenbuecher, Yvette Hoehn, Daniel Lipka, Helmut Thomas, Christoph Huber, Thomas Fischer
Journal: Blood (2005)
Activation of the NLRP1 Inflammasome Induces the Pyroptotic Death of Hematopoietic Progenitor Cells
Authors: Seth L. Masters, Mordechay Gerlic, Donald Metcalf, Simon P. Preston, Marc Pellegrini, Joanne A. O'Donnell, Kate McArthur, Tracey M. Baldwin, Stephane Chevrier, Cameron J. Nowell, Louise H. Cengia, Katya J. Henley, Janelle E. Collinge, Daniel L. Kastner, Lionel Feigenbaum, Douglas J. Hilton, Warren S. Alexander, Ben A. Croker, Benjamin T. Kile
Journal: Blood (2012)
MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study
Authors: Tamas Hickish, Thierry Andre, Lucjan Wyrwicz, Mark Saunders, Tomasz Sarosiek, Judit Kocsis, Radim Nemecek, Wojciech Rogowski, Krzysztof Lesniewski-Kmak, Lubos Petruzelka, Ron N Apte, Prasant Mohanty, Michael Stecher, John Simard, Aimery de Gramont
Journal: The Lancet Oncology (2017)
Survival Trends in Primary Myelodysplastic Syndromes: A Comparative Analysis of 1000 Patients By Year of Diagnosis and Treatment
Authors: Naseema Gangat, Mrinal M Patnaik, Kebede H. Begna, Aref Al-Kali, Mark R Litzow, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: Blood (2015)
Male Sex Is Associated with Lower Rituximab Trough Serum Levels and Evolves as a Significant Prognostic Factor in Elderly Patients with DLBCL Treated with R-CHOP: Results From 4 Prospective Trials of the German High-Grade Non-Hodgkin-Lymphoma Study Group (DSHNHL).
Authors: Michael Pfreundschuh, Niels Murawski, Samira Zeynalova, Viola Poeschel, Marcel Reiser, Anthony D. Ho, Christina Nickenig, Swen Wessendorf, Bernd Metzner, Sandra Grass, Joerg Schubert, Markus Loeffler, Norbert Schmitz
Journal: Blood (2009)
Antibody Against Macrophage Receptor with Collagenous Structure (Anti-MARCO IgG) in Thrombotic Thrombocytopenic Purpura Patients.
Authors: Phandee Watanaboonyongcharoen, Jessica L. Allen, Yuri D. Fedoriw, Herbert C. Whinna, Rommel P. Lu, Yara A. Park, Stefanie Sarantopoulos
Journal: Blood (2012)
Risk-Adapted Therapy in Younger Adults with Acute Myeloid Leukemia: Results of the AMLHD98A Trial of the AMLSG.
Authors: Richard F. Schlenk, Konstanze Dohner, Hans Pralle, Katharina Götze, Michael Pfreundschuh, Michael Kneba, Günther Gastl, Udo Germing, Detlef Haase, Hartmut Dohner
Journal: Blood (2006)
Angry GPs hit back at PM over seven day service threats
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The prime minister, Theresa May, has met with an angry backlash from GPs after she threatened to withhold funding from general practices that did not offer their patients longer opening hours.

GPs accused the government of scapegoating the profession and ignoring the true causes of the pressures across the NHS in England, after practices were warned through a series of inflammatory headlines in the national media that funding for extending their opening hours could be withheld unless they could prove that they were informing their patients of additional appointment slots and offering appointments at convenient times.123

May’s intervention came as the government came under growing pressure to tackle the growing crisis in hospital emergency departments by reducing the number of patients visiting.4

But GPs said that the prime minister was attempting to shift the blame away from the government and was wilfully ignoring the …
OC-047 New Platform for Trans-Anal Submucosal Endoscopic Resection- (TASER): Updated Clinical Results from Tertiary Centre
Authors: ZPP Tsiamoulos, R Rameshshanker, A Wawszczak, J Warusavitarne, BP Saunders
Journal: Gut (2016)

<h3>Introduction</h3> Current trans-anal surgical and advanced endoscopic resection procedures have the potential to resect complex rectal polyps (CRPs). However both approaches have limitations in terms of practicality and safety. <h3>Methods</h3> Consecutive patients (Jan13/April15), referred for the excision of CRPs, were being considered for proctectomy and/or had failed conventional endoscopic/trans-anal therapy. The GelPoint Path trans-anal access port allowed dynamic tissue manipulation to facilitate endoscopic-submucosal-dissection/ESD. Supplementary techniques were also used: piecemeal-endoscopic-mucosal-resection or ablation/P-EMR or EMA and trans-anal excision/TAE. The aim of this study was to evaluate the feasibility, technical success and safety profile of this new hybrid, endo-surgical Trans-Anal Submucosal Endoscopic Resection- (TASER) approach for CRPs. <h3>Results</h3> Thirty-two TASER procedures were employed in 31 patients (mean age 65 years/17 males-14 females) with 31 CRPs (mean size 8 cm/range 5 cm–18 cm). Complete endoscopic excision in a single session was achieved in 28/31 patients (93%); in one patient a second TASER session for completion of polypectomy, in another an elective laparoscopic-anterior-resection due to T1,sm3,N0,M0 and in a third patient a defunctioning-ileostomy due to intraperitoneal perforation before completion of polypectomy. Mean procedure time was 185 min, range 65–480 min. Thirty two TASER sessions were employed using ESD in 12/32, ESD+P-EMR in 6/32, ESD+P-EMR+EMA in 4/32, ESD+TAE in 3/32, ESD/P-EMR/TAE in 3/32 and ESD+P-EMR+EMA+TAE in 4/32. Intra-procedural bleeding was controlled with haemostatic endoscopic devices/surgical clipping. In 6/10 TASER-TAE cases there was a need for a full-thickness rectal dissection due to severe submucosal fibrosis: 4/6 cases were closed with surgical sutures/endoscopic clips and in 2/6 cases only endoscopic clips were deployed. Two episodes of delayed bleeding were reported with no transfusion/re-intervention requirement. All patients were discharged the day after the TASER apart from one patient who developed bacteremia requiring intravenous antibiotics/a 4 night hospital stay and the patient who required a defunctioning ileostomy, discharged on day 4 post-operation. First follow-up performed at 4–6 months interval in 25/31 patients showed: 21/25 with no recurrence/(84%) and 4/25/ (16%) with a minimal (&lt;15mm) polyp recurrence, amenable to endoscopic therapy. No rectal stricturing was identified and only one episode of transient faecal incontinence were reported. <h3>Conclusion</h3> TASER appears to be a safe and efficient endo-surgical approach providing an optimal platform for the minimally-invasive management of high- risk, complex rectal polyps. <h3>Disclosure of Interest</h3> None Declared
Additional Cytogenetic Abnormalities and/or Philadelphia Chromosome Metaphase Mosaicism Might Adversely Influence Survival and Imatinib Response in Chronic Myeloid Leukemia.
Authors: Andrew P. Landstrom, Rhett P. Ketterling, Ryan A. Knudson, Gordon W. Dewald, Ayalew Tefferi
Journal: Blood (2006)
Rapid BCP-ALL Engraftment in NOD/SCID Mice Is Characterized by a High Leukemia Initiating Cell (LIC) Frequency.
Authors: Luca Trentin, Manon Queudeville, Sarah M. Eckhoff, Felix Seyfried, Manuel Herrmann, Simone Miller, Nabiul Hasan, Klaus-Michael Debatin, Lueder H. Meyer
Journal: Blood (2012)
An Official American Thoracic Society Research Statement: Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling
Authors: Y. S. Prakash, Andrew J. Halayko, Reinoud Gosens, Reynold A. Panettieri, Blanca Camoretti-Mercado, Raymond B. Penn
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and development of therapeutics targeting AR and to propose approaches and solutions to these specific problems. This Statement is not intended to provide clinical practice recommendations on any disease in which AR is observed and/or plays a role.An international multidisciplinary group from within academia, industry, and the National Institutes of Health, with expertise in multimodal approaches to the study of airway structure and function, pulmonary research and clinical practice in obstructive lung disease, and drug discovery platforms was invited to participate in one internet-based and one face-to-face meeting to address the above-stated goals. Although the majority of the analysis related to AR was in asthma, AR in other diseases was also discussed and considered in the recommendations. A literature search of PubMed was performed to support conclusions. The search was not a systematic review of the evidence.Multiple conceptual, logistical, economic, and regulatory deterrents were identified that limit the performance of AR research and impede accelerated, intensive development of AR-focused therapeutics. Complementary solutions that leverage expertise of academia and industry were proposed to address them.To date, numerous factors related to the intrinsic difficulty in performing AR research, and economic forces that are disincentives for the pursuit of AR treatments, have thwarted the ability to understand AR pathology and mechanisms and to address it clinically. This ATS Research Statement identifies potential solutions for each of these factors and emphasizes the importance of educating the global research community as to the extent of the problem as a critical first step in developing effective strategies for: (1) increasing the extent and impact of AR research and (2) developing, testing, and ultimately improving drugs targeting AR.
Chronic Lymphocytic Leukemia Patients and Eµ-TCL1 Mice Share a Phenotype of Functional Granulocyte-like and Dysfunctional Monocyte-like Myeloid Derived Suppressor Cells
Authors: Gerardo Ferrer, Xiao-Jie Yan, Brendan Franca, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L Allen, Kanti R Rai, Nicholas Chiorazzi
Journal: Blood (2015)
High Frequency of AML1 Mutations in Patients with Chronic Myelomonocytic Leukemia.
Authors: Lee-Yung Shih, Chein-Fuang Huang, Der-Cherng Liang, Yu-Shu Shih, Jin-Hou Wu, Po Dunn, Po-Nan Wang, Ming-Chung Kuo
Journal: Blood (2005)
Usefulness of circulating tumor cell detection for the diagnosis of malignant pancreatic head tumors: A pilot study.
Authors: Julien Coget, France Blanchard, Aude Lamy, Emmanuel Toure, Helene Chiavelli, Paul Basile, Frédéric Di Fiore, Isabelle iwanicki-Caron, Pierre Michel, Francoise Lemoine, Jean-Christophe Sabourin
Journal: Journal of Clinical Oncology (2012)

235 Background: Pancreatic adenocarcinomas account for 90% of pancreatic malignancies. It is often diagnosed at an unresectable stage (at a metastatic and / or at a locoregional invasion stage). Histological diagnosis is mandatory to establish palliative chemotherapy. Endoscopic ultrasound-guided fine needle aspiration (EUGA) of pancreatic tumors is a difficult gesture, not without risk. Furthermore, it frequently provides pauci-cellular, hemorrhagic or necrotic material unsuitable for precise histologic diagnosis. Techniques for detecting circulating tumor cells (CTC) have been recently developed to highlight the presence of malignant cells circulating in peripheral blood. Screencells technology is based on the separation of CTCs from other circulating cells by blood filtration through a polycarbonate membrane with 7m pores. The aims of this pilot study were 1) to compare the results of detections CTC to EUGA, 2) to assess the feasibility and the contribution of this innovative technique in the care of a limited series of patients. Methods: A sample of peripheral venous blood was performed in 15 patients with a suspicious CT scan of a pancreatic head tumoral lesion, before the completion of an EUGA. 4 ml of blood were filtered using ScreencellsCyto columns. After Giemsa staining, a pathologist analyzed each filter. Cells visualized on the filter under light microscopy were considered as tumoral if they met the following morphological criteria: anisocytosis, anisokaryosis, nuclear diameter&gt;7m, nuclear membrane irregularitie, large nucleolus. Results: The malignant feature of the pancreatic lesion could be histologically assessed after liver biopsy for two patients. EUGA showed malignancy in 10 cases. CTC presence was identified in 7 patients with tumoral histological diagnosis. Conclusions: This study demonstrates the feasibility of CTC detection in patients with pancreatic head tumor. The identification of CTCs could facilitate patient care, thus avoiding difficult and potentially dangerous EUGA. A prospective trial is needed to confirm the positive predictive value of this biomarker and to evaluate its contribution in the diagnosis procedure of such tumors.
Defibrotide for the Treatment of Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome with/without Multi-Organ Dysfunction Following Chemotherapy: Results from an Ongoing Expanded Access Program
Authors: Nancy A. Kernan, Paul G. Richardson, Angela R. Smith, Brandon M. Triplett, Stephan A. Grupp, Joseph H. Antin, Leslie E. Lehmann, Wei Liang, Robin L. Hume, Alison L. Hannah, Bijan Nejadnik, Robert J. Soiffer
Journal: Blood (2015)
Successful Management (Mgt) of Hyperkalemia Associated with Tumor Lysis Syndrome (TLS) in Refractory Chronic Lymphocytic Leukemia (CLL) Patients (pts) Receiving Flavopiridol on an Active Pharmacologically Derived Schedule.
Authors: Mollie E. Moran, Beth Fischer, Sara Broering, Kristie A. Blum, Thomas S. Lin, John C. Byrd, Michael R. Grever, Michelle Brooker-McEldowney
Journal: Blood (2005)
Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients in First Complete Remission: Significant Impact of the Interval Between Diagnosis and Transplantation on Different Outcomes
Authors: Stéphanie Ducreux, Mohamad Sobh, Stéphane Morisset, Marie Balsat, Xavier Thomas, Caroline Lejeune, Sophie Ducastelle-Leprêtre, Fiorenza Barraco, Hélène Labussière-wallet, Franck E. Nicolini, Mauricette Michallet, Valérie Dubois
Journal: Blood (2015)
Development of Small Molecule Inhibitors of the AML1-ETO and CBFβ-SMMHC Oncoproteins.
Authors: Jolanta E. Grembecka, Kristin Graf, Yali Kong, Michael Douvas, Tomasz Cierpicki, Anuradha Illendula, Gwen Baber, Izabela Bielnicka, Liya Roudaia, Nancy A. Speck, Milton L. Brown, John H. Bushweller
Journal: Blood (2007)
Deferasirox (Exjade®) ≥30 Mg/Kg/Day Is Effective in Reducing Iron Burden in Thalassemia Major Patients Previously Chelated with Monotherapy or Combination Therapy.
Authors: Ali Taher, Mohsen Saleh Elalfy, Amal El-Beshlawy, Dunhua Zhou, Lee Lee Chan, Chi-Kong Li, Kai-Hsin Lin, John B. Porter, Pranee Sutcharitcharan, Dany Habr, Gabor Domokos, Bernard Roubert, M. Domenica Cappellini
Journal: Blood (2009)
Prognostic Significance of Magnetic Resonance Imaging (MRI) of Bone Marrow in Previously Untreated Patients with Multiple Myeloma.
Authors: Lia Angela Moulopoulos, Dimitra Gika, Kay Dellasale, Donna Weber, Athanasios Anagnostopoulos, Raymond Alexanian, Meletios A. Dimopoulos
Journal: Blood (2004)
The membrane‐bound O‐acyltransferase domain‐containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B
Authors: Khaled Thabet, Henry Lik Yuen Chan, Salvatore Petta, Alessandra Mangia, Thomas Berg, Andre Boonstra, Willem P. Brouwer, Maria Lorena Abate, Vincent Wai‐Sun Wong, Maiiada Nazmy, Janett Fischer, Christopher Liddle, Jacob George, Mohammed Eslam
Journal: Hepatology (2017)

Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patients underwent gene expression analysis to assess the functional consequences of rs641738 on hepatic MBOAT7 expression. The minor allele (T) of rs641738 was associated with greater inflammation (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.95; P = 0.001) and fibrosis (OR = 1.31; 95% CI, 1.19-1.92; P = 0.01). Risk allele frequency in whites (0.43) was greater than in Chinese (0.24), translating to a larger size effect in the former. The rs641738 (T) allele was associated with lower hepatic MBOAT7 expression (P = 0.008), and the latter was associated with serum liver enzymes and inflammation. Neither patatin-like phospholipase domain-containing protein 3 rs738409 nor transmembrane 6 superfamily member 2 rs58542926 polymorphisms influenced disease severity.In patients with CHB, MBOAT7 rs641738 influences hepatic inflammation and fibrosis stage. (Hepatology 2017;65:1840-1850).