tbuckley/cabot-search huggingface dataset:
High Efficiency Clinical Scale Selective Depletion of Alloreacting T Cells Using Expanded T Lymphocytes as Antigen-Presenting Cells and a TH9402-Based Photodepletion Technique in HLA-Mismatched and Matched Donor-Recipient Pairs.
Authors: Stephan Mielke, Raquel Nunes, Katayoun Rezvani, Vicki S. Fellowes, Yong Fan, Scott R. Solomon, Christian Scotto, Elizabeth J. Read, A. John Barrett
Journal: Blood (2006)
Lenalidomide (LEN) Combined to Intensive Chemotherapy (IC) in AML and Higher Risk MDS with Del 5q. Interim Results of a Phase I/II Study.
Authors: Lionel Ades, Aspasia Stamatoullas, Emmanuel Raffoux, Thomas Prebet, Pascal Lenain, Romain Guieze, Mathilde Hunault, Eric Wattel, Laurence Stalnikiewicz, Krimo Bouabdallah, Vincent Levy, Norbert Vey, Herve Dombret, Simone Boehrer, Claude Gardin, Pierre Fenaux
Journal: Blood (2009)
S37 The persistence of eosinophilic inflammation in copd over time – aeris cohort
Authors: VL Kim, NP Williams, KK Ostridge, MM Naghibi, NA Coombs, JM Devaster, E Aris, SC Clarke, AC Tuck, SA Wootton, SC Bourne, KJ Staples, TM Wilkinson
Journal: Thorax (2016)

<h3>Introduction</h3> The importance of eosinophilic inflammation in COPD is in its ability to predict an enhanced response to treatment, such as corticosteroids. However, little is know about the persistence of higher eosinophils, or its associations with infectious aetiology during clinical stability and exacerbation. We investigated the natural history of eosinophilic inflammation over time and studied eosinophil-associated acute exacerbations of COPD and the impact of seasonality in a cohort of COPD patients. <h3>Methods</h3> 127 subjects with moderate to very severe COPD were enrolled into the AERIS cohort (NCT01360398) and were reviewed monthly for scheduled visits and during exacerbations. Blood sampling was performed quarterly and at exacerbations. Higher blood eosinophils (BE) were defined as ≥2%. Based on frequency of higher BE over the study, subjects were divided into predominantly (PE), intermittent (IE) and rarely eosinophilic (RE) groups. <h3>Results</h3> Blood eosinophil levels ≥2% were prevalent at baseline (68.3%) and at exacerbations (51.1%). Over the study 57.6% of subjects had predominantly, 16.16% intermittently and 26.26% rarely ≥2% blood eosinophils. Higher BE at enrolment was strongly associated with a predominantly high BE profile for the year (AUC 0.841 p &lt; 0.001) and with greater odds of ≥2% eosinophils at exacerbation (OR 9.60 p &lt; 0.001). The odds of ≥2% BE at exacerbation were higher in the PE group compared to the rarely group (OR 12.00, p &lt; 0.001). A larger proportion of exacerbations were eosinophilic in the Summer than Winter (OR 2.57, p = 0.001). The odds of bacterial presence at exacerbation was higher in Winter than Summer among those in the PE group (OR 4.74, CI: 1.43; 15.71, p = 0.011), but not among those in the RE group (OR 1.15, CI: 0.29; 4.56, p = 0.838). <h3>Conclusion</h3> Our data suggests that it is possible to stratify COPD patients by stable state blood eosinophil levels. This measure is easily accessible and provides important insights into the longitudinal inflammatory phenotype of COPD. Persistent higher blood eosinophil levels were associated with risk of bacterial infection at exacerbation, and seasonality of exacerbation. Intervention studies are required to establish clear treatment algorithms utilising this measure to stratify therapy.
Wharton's Jelly- MSC As Effective Tool for Expansion of Purified Human Cord Blood CD34+ Hematopoietic Stem Cells
Authors: Melania Lo Iacono, Elena Baiamonte, Rosalia Di Stefano, Barbara Spina, Massimiliano Sacco, Rosario Di Maggio, Angela Vitrano, Aurelio Maggio, Santina Acuto
Journal: Blood (2015)
Knockout of the primary sclerosing cholangitis‐risk gene Fut2 causes liver disease in mice
Authors: Luca Maroni, Simon D. Hohenester, Stan F.J. van de Graaf, Dagmar Tolenaars, Krijn van Lienden, Joanne Verheij, Marco Marzioni, Tom H. Karlsen, Ronald P.J. Oude Elferink, Ulrich Beuers
Journal: Hepatology (2017)

The etiopathogenesis of primary sclerosing cholangitis is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factors for primary sclerosing cholangitis. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2-/- mice. Fut2-/- mice were viable and fertile, had lower body weight than wild-type (wt) littermates and gray fur. Half of the Fut2-/- mice showed serum bile salt levels 40 times higher than wt (Fut2-/-high ), whereas the remainder were normocholanemic (Fut2-/-low ). Fut2-/- mice showed normal serum liver tests, bile flow, biliary bile salt secretion, fecal bile salt loss, and expression of major hepatocellular bile salt transporters and cytochrome P450 7a1, the key regulator of bile salt synthesis, indicating that elevated serum bile salts in Fut2-/-high mice were not explained by cholestasis. Fut2-/-high mice, but not Fut2-/-low mice, were sensitive to hydrophobic bile salt feeding (0.3% glycochenodeoxycholate); they rapidly lost weight and showed elevation of serum liver tests (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) and areas of liver parenchymal necrosis. Histomorphological evaluation revealed the presence of paraportal shunting vessels, increased numbers of portal vascular structures, wall thickening of some portal arteries, and periductal fibrosis in Fut2-/-high mice more than Fut2-/-low mice and not wt mice. Unconjugated bilirubin and ammonia were or tended to be elevated in Fut2-/-high mice only. Portosystemic shunting was demonstrated by portal angiography, which disclosed virtually complete portosystemic shunting in Fut2-/-high mice, discrete portosystemic shunting in Fut2-/-low mice, and no shunting in wt littermates.Liver pathology in Fut2-/- mice is dominated by consequences of portosystemic shunting resulting in microcirculatory disturbances, mild (secondary) periductal fibrosis, and sensitivity toward human bile salt toxicity. (Hepatology 2017;66:542-554).
Gastric HER2 testing study (GaTHER): Evaluation of gastric cancer testing accuracy in Australia.
Authors: M. P. Kumarasinghe, A. Morey, M. Bilous, S. B. Fox
Journal: Journal of Clinical Oncology (2011)

15 Background: Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in 6%-33% of advanced gastric cancers (GC), and trastuzumab, an anti-HER2 monoclonal antibody, has been shown to provide a survival benefit in HER2-positive disease. Thus accurate testing will be critical to ensure HER2 utility as a predictive marker in GC. HER2 in situ hybridisation (ISH) testing is currently undertaken for all breast cancer in Australia as part of a national program, however pathologists have limited experience with GC tissue. This study evaluated testing methods and determined inter-laboratory reproducibility of HER2 scoring in GC across 9 Australian reference laboratories. Methods: A tissue microarray (TMA) comprising 100 pre-screened gastric or gastro-oesophageal junction (GOJ) adenocarcinoma samples with a range of HER2 positivity was prepared from 1-mm cores. Each laboratory assessed TMA HER2 status by both immunohistochemistry (IHC) (n=9) and ISH [chromogenic (n=3), silver (n=6), fluorescent (n=1)], using its validated testing methods and applying GC scoring criteria. Inter-laboratory agreement on HER2 ISH scoring, using both HER2 copy number and HER2:chr17 ratio, and agreement on IHC scoring (ToGA method), was calculated (kappa statistics). Results: There was only moderate agreement between laboratories on IHC scoring (κ = 0.46). Agreement on CISH/SISH scoring was good/very good when HER2 copy number, stratified into negative, equivocal and positive for amplification, was used (κ = 0.68-0.86), but was reduced when HER2:chr17 ratio was used (κ = 0.59-0.70). Agreement between CISH/SISH and FISH using HER2 copy number was excellent (κ = 0.88-0.91) but was again reduced when HER2:chr17 ratio was used (κ = 0.84-0.86). Good/very good agreement between IHC and FISH (κ = 0.85) or CISH/SISH (κ = 0.72-0.87) was also achieved when HER2 copy number was used. Conclusions: Good concordance across laboratories can be achieved with FISH, or single-probe CISH or SISH, scored using HER2 copy number, with use of chr17 probe in chromogenic assays best restricted to equivocal cases. HER2 IHC alone is not recommended for determining HER2 status in gastric and GOJ cancers. [Table: see text]
P3.04-011 Salvage Surgery for Isolated Local Recurrence after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small Cell Lung Cancer
Authors: Hiroshi Date, Masatsugu Hamaji, Yukinori Matsuo, Akihiko Yoshizawa, Toshi Menju, Toyofumi Chen-Yoshikawa
Journal: Journal of Thoracic Oncology (2017)
Signaling Pathways of All-Trans Retinoic Acid (ATRA)-Induced Apoptosis in Mantle Cell Lymphoma (MCL).
Authors: Amareshwar T.K. Singh, Savita Bhalla, Robert O. Ryan, Thanh-Son Nguyen, Karthik T.K. Singh, Andrew M. Evens, Leo I. Gordon
Journal: Blood (2007)
The International Multiple Myeloma Research (IMMEnSE) Consortium: Genetics of Multiple Myeloma Risk and Prognosis
Authors: Federico Canzian, Katia Beider, Gabriele Buda, Felipe de Arriba de la Fuente, Marek Dudzinski, Charles Dumontet, Ramon Garcia-Sanz, Hiroshi Handa, Krzysztof Jamroziak, Manuel Jurado, Artur J. Jurczyszyn, Stefano Landi, Fabienne Lesueur, Herlander Marques, Joaquín Martínez-López, Victor Moreno, Hirokazu Murakami, Arnon Nagler, Mario Petrini, Rui Manuel Reis, Rafael Rios, Juan Sainz, Zofia Szemraj-Rogucka, Annette Juul Vangsted, Judit Varkonyi, Ulla Vogel, Marzena Watek, Daniele Campa
Journal: Blood (2014)
The combination of cyclosporine and mycophenolate mofetil is less effective than cyclosporine and methotrexate in the prevention of acute graft‐versus host disease after stem‐cell transplantation from unrelated donors
Authors: Ronit Yerushalmi, Noga Shem‐Tov, Ivetta Danylesko, Roni Shouval, Arnon Nagler, Avichai Shimoni
Journal: American Journal of Hematology (2017)

Acute graft-versus-host disease (GVHD) is the major treatment-related complication after stem-cell transplantation (SCT) from unrelated-donors. Several GVHD prophylaxis regimens have been explored, but no regimen has shown superiority. We analyzed transplantation outcomes in 472 consecutive unrelated-donor SCT recipients, using cyclosporine/methotrexate (MTX, n = 314) or cyclosporine/mycophenolate-mofetil (MMF, n = 158) for GVHD prophylaxis. Neutrophil engraftment was faster after MMF, days 11 and 14, respectively (P = .001). Acute GVHD grade II-IV and III-IV occurred in 47% and 28% after MMF compared to 27% and 12% after MTX, respectively (P < .001). Nonrelapse mortality (NRM) was 44% and 24%, respectively (P < .001). Death associated with GVHD occurred in 25% and 8% (P < .0001), while other NRM causes occurred in 19% and 16%, respectively (P = .39). Relapse mortality was similar. Overall survival was better after MTX, 40% and 29%, respectively (P = .006). However, this difference had only borderline significance when adjusting for differences in patient characteristics (HR, 1.3, P = .08). To minimize potential selection bias we analyzed outcomes on the basis of an intention-to-treat like analysis. During the years 2008-2009, the leading GVHD prophylaxis regimen for unrelated-donor SCT included MMF (89% of transplants). During the other periods, MTX was used predominantly (82% of transplants). The two periods were otherwise well-matched. Acute GVHD occurred more often in 2008-2009. Death associated with GVHD occurred more often, while other NRM causes occurred less often resulting in similar NRM and overall survival. In conclusion, cyclosporine/MMF is associated with faster engraftment and possibly with less organ toxicity than cyclosporine/MTX. However, it is associated with increased rates of acute GVHD and GVHD-associated deaths.
Pharmacokinetics of Arsenic Species with Relapsed or Refractory Acute Promyelocytic Leukemia (APL) Treated with Arsenic Trioxide (ATO) in Japanese Patients.
Authors: Kazuyuki Shigeno, Miki Kobayashi, Naohi Sahara, Satoki Nakamura, Shinya Fujisawa, Kensuke Naito, Kaori Shinjo, Akihiro Takeshita, Ryuzo Ohno, Kenji Kinoshita, Masahito Shimoya, Toshikazu Kaise, Kazunori Ohnishi
Journal: Blood (2005)
Identification of Patient Subgroups Demonstrating Longer Progression-Free Survival (PFS) Benefit with Bortezomib-Rituximab Versus Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma (FL): Biomarker Analyses of the Phase 3 LYM3001 Study
Authors: Bertrand Coiffier, Weimin Li, Erin D Henitz, J. D. Karkera, Reyna Favis, Dana Gaffney, Alice Shapiro, Panteli Theocharous, Yusri A Elsayed, Helgi van de Velde, Evgenii A Osmanov, Xiaonan Hong, Adriana Scheliga, Fritz C. Offner, Simon Rule, Adriana C Teixeira, Jan Walewski, Sven de Vos, Michael Crump, Ofer Shpilberg, Pier Luigi Zinzani, Andrew Z Cakana, Dixie-Lee Esseltine, George Mulligan, Deborah S Ricci
Journal: Blood (2011)
CCBE1 mutation causing sclerosing cholangitis: Expanding the spectrum of lymphedema‐cholestasis syndrome
Authors: André Viveiros, Marion Reiterer, Benedikt Schaefer, Armin Finkenstedt, Stefan Schneeberger, Hubert Schwaighofer, Patrizia Moser, Rudolf Sprenger, Bernhard Glodny, Wolfgang Vogel, Andreas R. Janecke, Heinz Zoller
Journal: Hepatology (2017)

A 52‐year old patient presented with lymphedema, protein loosing enteropathy, and sclerosing cholangitis and was diagnosed with lymphedema cholestasis syndrome (LCS). Cholangioscopy revealed dilated lymphatic vessels obstructing the bile duct and compound heterozygosity for collagen and calcium‐binding epidermal growth factor domain‐containing protein 1 ( CCBE1 ) mutations was identified defining a novel type of LCS. (H epatology 2017;66:286–288).
Pediatric Acute Myeloid Leukemia with Nucleophosmin Mutations Is Characterized by a Gene Expression Signature with Dysregulated HOX Gene Expression Distinct from MLL-Rearranged Leukemias.
Authors: Charles G. Mullighan, Alyssa L. Kennedy, Xiaodong Zhou, Sheila A. Shurtleff, James R. Downing
Journal: Blood (2005)
Epidermal growth factor-mediated signaling in ovarian cancer and the role of miR-34a and 6p22 gene amplification-based E2F3a control.
Authors: D. Reimer, H. Kiefel, M. Hubalek, M. Erdel, N. Concin, G. Hofstetter, E. Mueller-Holzner, P. Altevogt, C. Marth, A. G. Zeimet
Journal: Journal of Clinical Oncology (2011)

e15535 Background: Cell cycle acceleration based on a selective induction of proliferation-promoting transcription factor E2F3a is a crucial step in EGFR mediated mitogenic signalling in ovarian cancer. Herein we report on the molecular background and clinical relevance of two alternative mechanisms of E2F3a control. One is acting epigenetically via promoter methylation of miR-34a, which by its physical interaction with E2F3a transcripts causes their degradation, and the second is based on 6p22 gene locus amplification. Methods: Expression levels of E2F3 isoforms and miR-34a were estimated by RT-PCR, miR-34a promoter methylation status by means of MethyLight-PCR. MiRIDIAN based knockdown or induction of miR-34a was performed in ovarian cancer cell lines and FISH analyses were used to estimate 6p22 amplification status in cell lines and primary tumor specimens. The clinical relevance of miR-34a and 6p22 amplification was evaluated in a large collective of 130 ovarian cancer patients. Results: MiRIDIAN-based knock-down or induction of miR-34a evidenced a direct regulatory link between miR-34a and E2F3a, and the tumor-suppressive character of miR-34a was documented by its inverse correlation with grading (p=0.016), residual disease (p=0.013) and association with improved survival. We further showed that in a significant number of ovarian cancer specimens miR-34a depletion is based on promoter methylation. Although, 6p22 gene locus amplification was detected in a significant number of ovarian cancer specimens and correlated with grading (p=0.04) and FIGO (p=0.007), 6p22 ploidy was not relevant in predicting survival. In the Cox regression analysis E2F3a, but not activated EGFR or miR-34a expression, retained independent prognostic significance (progression-free survival: HR 3.785, p=0.013; overall survival: HR 4.6511; p=0.013). Conclusions: These clinical findings highlight the relevance of E2F3a in the biology of ovarian cancer. Moreover, identification of EGFR-independent mechanisms in E2F3a control can be helpful in explaining non-responsiveness of therapeutic EGFR targeting in ovarian cancer.
P155 Safety of tiotropium respimat® add-on therapy in patients aged 6–17 years with symptomatic asthma
Authors: C Vogelberg, SJ Szefler, E Hamelmann, A Boner, P Moroni-Zentgraf, M Engel, G El Azzi, H Finnigan, M Vandewalker
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Two Phase II trials have shown tiotropium Respimat® (tioR) to be a well-tolerated bronchodilator in patients aged 12–17<sup>1</sup> and 6–11<sup>2</sup> years with symptomatic asthma. Here, we further assessed the safety and tolerability of once-daily (QD) tioR add-on therapy in Phase III trials in patients aged 6–17 years with symptomatic asthma. <h3>Methods</h3> Data was analysed from three completed Phase III, randomised, double-blind, placebo-controlled, parallel-group trials: VivaTinA (NCT01634152), 12-week trial, patients aged 6–11 years; PensieTinA (NCT01277523), 12-week trial, patients aged 12–17 years; RubaTinA (NCT01257230), 48-week trial, patients aged 12–17 years. Patients received QD tioR 5 μg (2 puffs, 2.5 µg), QD tioR 2.5 μg (2 puffs, 1.25 µg) or QD placebo Respimat® (pboR; 2 puffs) as add-on to background therapy. Adverse events (AEs) were recorded and analysed descriptively by age: 6–11 years; 12–17 years. <h3>Results</h3> 1189 patients were treated: 6–11 years, n = 400; 12–17 years, n = 789. The frequency of patients with AEs was similar across all treatment arms, with a low incidence of drug-related and serious AEs; asthma and decreased peak expiratory flow rate were the most common AEs (Table). No deaths occurred. <h3>Conclusion</h3> The AE profile and AE incidences were similar between tioR 5 µg, tioR 2.5 µg and pboR, as add-on to inhaled corticosteroid ± other controllers, in patients aged 6–17 years with symptomatic asthma. <h3>References</h3> Vogelberg C, <i>et al</i>. <i>Respir Med</i> 2014;<b>108</b>:1268–76. Vogelberg C, <i>et al</i>. <i>Respir Res</i> 2015;<b>16</b>:20.
Molecular and Genetic Characterization of Fit, Elderly Patients Receiving Oral Fludarabine, Oral Cyclophosphamide and Intravenous Rituximab (OFOCIR) As Initial Treatment of Chronic Lymphocytic Leukemia (CLL)
Authors: Xavier C Badoux, Giles Best, Sara Gabrielli, Melanie Hayes, Ying Zhu, Stephen Mulligan, Bryone J Kuss
Journal: Blood (2014)
MA01.07 Influence of Nodule Morphology on Inter-Reader Variability of Volume and Diameter Measurements in CT Lung Cancer Screening
Authors: Marjolein Heuvelmans, Daiwei Han, Rozemarijn Vliegenthart, Gonda De Jonge, Joan Walter, Peter Van Ooijen, Harry De Koning, Matthijs Oudkerk
Journal: Journal of Thoracic Oncology (2017)
Multicenter, Prospective Study of Tacrolimus Plus Methotrexate As Graft-Versus-Host Disease Prophylaxis in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation: Comparison with Cyclosporine Group As Control
Authors: SeungHwan Shin, JaeHo Yoon, SeungAh Yahng, SungEun Lee, ByungSik Cho, KiSung Eom, YooJin Kim, Seok Lee, ChangKi Min, HeeJe Kim, SeokGoo Cho, DongWook Kim, WooSung Min, ChongWon Park, JongWook Lee
Journal: Blood (2012)
Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra
Authors: Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M. Frampton, James X. Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L. Erlich, Jeffrey S. Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A. Miller, Philip J. Stephens, Katherine A. Janeway, John M. Maris, Soheil Meshinchi, Trevor J. Pugh, Jack F. Shern, Doron Lipson
Journal: Cancer Research (2017)

Abstract Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant. We identified novel ALK fusions in a neuroblastoma (BEND5–ALK) and an astrocytoma (PPP1CB–ALK), novel BRAF fusions in an astrocytoma (BCAS1–BRAF) and a ganglioglioma (TMEM106B–BRAF), and a novel PAX3–GLI2 fusion in a rhabdomyosarcoma. Previously characterized ALK, NTRK1, and PAX3 fusions were observed in unexpected malignancies, challenging the "disease-specific" alterations paradigm. Finally, we identified recurrent variants of unknown significance in MLL3 and PRSS1 predicted to have functional impact. Data from these 1,215 tumors are publicly available for discovery and validation. Cancer Res; 77(2); 509–19. ©2017 AACR.
Long-Term Outcome to First-Line Imatinib according to 2013 European LeukemiaNet Response Criteria: a GIMEMA CML WP Analysis
Authors: Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Fabio Stagno, Alessandra Iurlo, Francesco Albano, Elisabetta Abruzzese, Bruno Martino, Luciano Levato, Tamara Intermesoli, Patrizia Pregno, Giuseppe Rossi, Filippo Gherlinzoni, Pietro Leoni, Francesco Cavazzini, Dario Ferrero, Emilio Usala, Monica Bocchia, Mario Tiribelli, Enrico Montefusco, Simona Sica, Claudia Venturi, Simona Soverini, Michele Cavo, Giuliana Alimena, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2015)