tbuckley/cabot-search huggingface dataset:
A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells
Authors: Mariusz Z. Ratajczak, Janina Ratajczak, Malwina Suszynska, Donald M. Miller, Magda Kucia, Dong-Myung Shin
Journal: Circulation Research (2017)

Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed SCs (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs, epiblast SCs, and primordial germ cells suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review, we will critically discuss all these questions and the concept that small dormant SCs related to migratory primordial germ cells, described as very small embryonic-like SCs, are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue-committed SCs and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human very small embryonic-like SC in chemically defined media free from feeder-layer cells open up new and exciting possibilities for their application in regenerative medicine.
Genome-Wide Screening for Dominant Modifiers in Drosophila Identified New Cluster of Genes Involved in BCR-ABL Signalling and CML Progression.
Authors: Francesca Messa, Monica Pradotto, Francesca Arruga, Roberto Bernardoni, Enrico Bracco, Chiara Maffè, Emanuela Messa, Sonia Carturan, Elisabetta Signorino, Elisabetta Greco, Antonia Rotolo, Ilaria Iacobucci, Giovanni Martinelli, Giuseppe Saglio, Daniela Cilloni
Journal: Blood (2009)
P2.02-029 Concomitant ChemoRadiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase II Study from the Galician Lung Cancer Group
Authors: Susana Gómez, Carmen Areses, Natalia Fernandez, Jorge Garcia, Marinha Costa, Jose Luis Fírvida, Begoña Campos, Elena Hernandez, Begoña Taboada, Enrique Castro, Maria Veiras, Javier Afonso, Cristina Azpitarte, Margarita Amenedo, Joaquin Casal Rubio
Journal: Journal of Thoracic Oncology (2017)
Relapse risk and survival in patients with FLT3 mutated acute myeloid leukemia undergoing stem cell transplantation
Authors: Sameh Gaballa, Rima Saliba, Betul Oran, Jonathan E. Brammer, Julianne Chen, Gabriela Rondon, Amin M. Alousi, Partow Kebriaei, David Marin, Uday R. Popat, Borje S. Andersson, Elizabeth J. Shpall, Elias Jabbour, Naval Daver, Michael Andreeff, Farhad Ravandi, Jorge Cortes, Keyur Patel, Richard E. Champlin, Stefan O. Ciurea
Journal: American Journal of Hematology (2017)

Abstract In patients with AML with FMS‐like tyrosine kinase 3 ( FLT3 ) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3 ‐AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n = 119), high‐risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR‐HR, n = 31), and morphological evidence of active disease (AD, n = 50). The median follow‐up was 27 months, and the 2‐year overall and progression‐free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR‐HR FLT3 MRD positive group (72%), followed by CR‐HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre‐transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3 ‐AML.
Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) + Rituximab In Relapsed DLBCL Patients Followed by Stem Cell Transplantation: Preliminary Safety and Efficacy
Authors: Nina Wagner-Johnston, Andre Goy, Tatyana Feldman, Yeow Tee Goh, Cheolwon Suh, John William Sweetenham, Christine Powell, Sharon T. Sullivan, Erik R. Vandendries, Christian Gisselbrecht
Journal: Blood (2010)
Hematopoietic Cell Transplantation – Specific Comorbidity Index As An Instrument to Predict Survival in Patients Admitted to Intensive Care Unit Early After Allogeneic Transplantation
Authors: Ulas D. Bayraktar, Elizabeth J Shpall, Ping Liu, Stefan O Ciurea, Marcos De Lima, Gabriela Rondon, Kristen J Price, Richard Champlin, Joseph L Nates
Journal: Blood (2011)
P2.06-031 QUADRUPLE THREAT: A Pilot Phase 2 Study of RRx-001 in Advanced Lung Cancer Prior to Re-Administration of Platinum Doublets
Authors: Christina Brzezniak, Mary Quinn, Karen Zeman, Bryan Oronsky, Jan Scicinski, Scott Caroen, Nacer Abrouk, Aiste Degesys, Bruno Schmitz, Paul Peterson, Joe Roswarski, Jane Trepel, Min-Jung Lee, Sunmin Lee, Yusuke Tomita, Regina Day, Saheli Jha, Corey Carter
Journal: Journal of Thoracic Oncology (2017)
The Natural History of RTQ-PCR Levels After the Achievement of Complete Molecular Remission (CMR): Implications for ‘Stopping' Studies
Authors: Dragana Milojkovic, Gareth Gerrard, Christos Paliompeis, Marco Bua, Alistair Reid, Mary Alikian, Jamshid Khorashad, John M Goldman, David Marin, Letizia Foroni, Jane F Apperley
Journal: Blood (2011)
P3.02c-098 An Observational Study of the Efficacy and Safety of Nivolumab in Patients with Advanced NSCLC. A Galician Lung Cancer Group
Authors: Rosario García Campelo, Maria Carmen Areses, Francisco Baron, Francisco Afonso-Afonso, Marinha Costa, Natalia Fernandez, Margarita Amenedo, Guillermo Alonso-Jaudenes Curvera, Maria Vázquez, Rocio Vilchez Simo, Joaquin Mosquera Martinez, Jorge Garcia, Susana Gómez, Begoña Campos, Jesus Garcia Mata, Urbano Anido Herranz, Jose Luis Fírvida
Journal: Journal of Thoracic Oncology (2017)
A Targeted and Stable Polymeric Nanoformulation Enhances Systemic Delivery of mRNA to Tumors
Authors: Qixian Chen, Ruogu Qi, Xiyi Chen, Xi Yang, Sudong Wu, Haihua Xiao, Wenfei Dong
Journal: Molecular Therapy (2017)

The high vulnerability of mRNA necessitates the manufacture of delivery vehicles to afford adequate protection in the biological milieu. Here, mRNA was complexed with a mixture of cRGD-poly(ethylene glycol) (PEG)-polylysine (PLys) (thiol) and poly(N-isopropylacrylamide) (PNIPAM)-PLys(thiol). The ionic complex core consisting of opposite-charged PLys and mRNA was crosslinked though redox-responsive disulfide linkage, thereby avoiding structural disassembly for exposure of mRNA to harsh biological environments. Furthermore, PNIPAM contributed to prolonged survival in systemic circulation by presenting a spatial barrier in impeding accessibility of nucleases, e.g., RNase, due to the thermo-responsive hydrophilic-hydrophobic transition behavior upon incubation at physiological temperature enabling translocation of PNIPAM from shell to intermediate barrier. Ultimately, the cRGD ligand attached to the formulation demonstrated improved tumor accumulation and potent gene expression, as manifested by virtue of facilitated cellular uptake and intracellular trafficking. These results indicate promise for the utility of mRNA as a therapeutic tool for disease treatment. The high vulnerability of mRNA necessitates the manufacture of delivery vehicles to afford adequate protection in the biological milieu. Here, mRNA was complexed with a mixture of cRGD-poly(ethylene glycol) (PEG)-polylysine (PLys) (thiol) and poly(N-isopropylacrylamide) (PNIPAM)-PLys(thiol). The ionic complex core consisting of opposite-charged PLys and mRNA was crosslinked though redox-responsive disulfide linkage, thereby avoiding structural disassembly for exposure of mRNA to harsh biological environments. Furthermore, PNIPAM contributed to prolonged survival in systemic circulation by presenting a spatial barrier in impeding accessibility of nucleases, e.g., RNase, due to the thermo-responsive hydrophilic-hydrophobic transition behavior upon incubation at physiological temperature enabling translocation of PNIPAM from shell to intermediate barrier. Ultimately, the cRGD ligand attached to the formulation demonstrated improved tumor accumulation and potent gene expression, as manifested by virtue of facilitated cellular uptake and intracellular trafficking. These results indicate promise for the utility of mRNA as a therapeutic tool for disease treatment.
Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats
Authors: Mohammed K. Hankir, Florian Seyfried, Constantin A. Hintschich, Thi-Ai Diep, Karen Kleberg, Mathias Kranz, Winnie Deuther-Conrad, Luis A. Tellez, Michael Rullmann, Marianne Patt, Jens Teichert, Swen Hesse, Osama Sabri, Peter Brust, Harald S. Hansen, Ivan E. de Araujo, Ute Krügel, Wiebke K. Fenske
Journal: Cell Metabolism (2017)
Genotype-Phenotype Associations in Patients with Severe Congenital Neutropenia.
Authors: Philip S. Rosenberg, Steven Stein, Elin Rodger, Audrey Anna Bolyard, Mary Ann Bonilla, Yigal Dror, George Kannourakis, Peter E. Newburger, Laurence A. Boxer, Blanche P. Alter, David C. Dale
Journal: Blood (2006)
Dose Escalation Study To Evaluate Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and Safety of Alemtuzumab for Consolidation Therapy in Patients with Chronic Lymphoycytic Leukemia: Phase I/II Trial of the German CLL Study Group (GCLLSG).
Authors: Kirsten Fischer, Carmen D. Schweighofer, Matthias Ritgen, Sebastian Boettcher, Elena Scharf, Barbara F. Eichhorst, Raymonde Busch, Wolfgang Abenhardt, Michael Kneba, Michael Hallek, Clemens-Martin Wendtner
Journal: Blood (2007)
A Phase I Trial of Bexarotene, a Retinoid X Receptor Agonist, in non-M3 Acute Myeloid Leukemia: Evidence of Myeloid Differentiation and Clinical Activity.
Authors: Donald E. Tsai, Selina Luger, Allison Kemner, Alison W. Loren, Cezary Swider, Ami Goradia, Charalambos Andreadis, Richard G. Ghalie, James Thompson, David Porter, Edward A. Stadtmauer, Stephen J. Schuster, Alexander Perl, Adam Bagg, Steven Goldstein, Martin Carroll
Journal: Blood (2006)
Clofarabine-Melphalan-Alemtuzumab Conditioning for Allogeneic Hematopoietic Cell Transplantation (Hct) in Patients with Advanced Hematologic Malignancies: A Phase I–II Study
Authors: Koen Van Besien, Frederick Locke, Justin Kline, Lucy Godley, Richard A. Larson, Olatoyosi Odenike, Elizabeth Shima Rich, Wendy Stock, Amittha Wickrema, Andrew Artz
Journal: Blood (2008)
BRCA1 expression and efficacy of vinorelbine in malignant mesothelioma.
Authors: S. Busacca, S. G. Gray, I. Paul, N. McTavish, K. J. O'Byrne, J. E. Quinn, D. A. Fennell
Journal: Journal of Clinical Oncology (2011)

e13541 Background: Malignant mesothelioma is an aggressive tumor refractory to current therapies and this may be due to intrinsic apoptosis resistance. Vinorelbine has been shown to exhibit useful clinical activity in phase II trials and showed a trend to improved survival as front-line monotherapy in the MS01 phase III study. BRCA1 has been reported to regulate sensitivity to microtubule poisons; however its involvement in regulating apoptosis in Mesothelioma has not been investigated. We have hypothesised that loss of BRCA1 confers resistance to vinorelbine induced apoptosis. Methods: Dose-response curves were generated by vialight assay and caspase-3 activity determined by luminescence assay. Three resistant cell lines were generated by increasing exposure to vinorelbine. Cells were transfected with 10nM non-targeting siRNA or BRCA1/Caspase8 siRNA. The percentage of apoptotic cell population was determined by PI staining and measurement of hypodiploidy. Results: Vinorelbine induced cytotoxicity correlated with BRCA1 expression level in a panel of 6 mesothelioma cell lines. We then investigated the effect BRCA1 silencing on vinorelbine sensitivity. The downregulation blocked caspase-3 activation, PARP cleavage and the percentage of subG1 cell population. Moreover, when cells were selected for resistance to vinorelbine, this was associated with a reduction in BRCA1 expression compared to parental cells. BRCA1 mRNA expression was not altered as shown by gene expression analysis, suggesting a post-transcriptional regulation mechanism. Data obtained in BAX/BAK double negative cells show that vinorelbine mediates toxicity irrespective of a functional mitochondrial apoptosis pathway, however caspase 8 can be activated in these cells; furthermore silencing of Caspase8 induced resistance to apoptosis by vinorelbine. We are addressing the prevalence of BRCA1 negativity in primary mesotheliomas including vinorelbine responders vs non-responders to delineate its potential as a predictive biomarker and will present these results. Conclusions: Our data highlight the BRCA1 as a candidate predictive biomarker for vinorelbine induced apoptosis suggesting a potential utility in personalising therapy with this agent.
Total venous capacity in two-kidney, one clip goldblatt hypertensive rats.
Authors: Jin Yamamoto, Koichi Ogino
Journal: Circulation (1982)

To assess possible time-related changes in total venous capacity, mean circulatory filling pressure (MCFP) and blood volume (BV, Evans blue) were determined in conscious rats with early, intermediate and chronic phases of two-kidney, one clip Goldblatt hypertension. MCFP, an index of whole-body venous activity, was measured while the circulation was arrested by the brief inflation of a balloon inserted into the right atrium. Compared with sham-operated control rats, Goldblatt rats showed unchanged MCFP and BV in early phase, unchanged MCFP with marginally (0.05 < p < 0.10) decreased BV in intermediate phase, and significantly (p < 0.05) increased MCFP with unchanged BV in chronic phase. Thus, decreased total venous capacity, which is reflected in increased MCFP relative to BV, occurred with a continuation of hypertension. MCFP/BV curves, obtained by measuring MCFP before and after rapid BV change, appeared to shift toward the pressure axis in all Goldblatt groups. There were no significant differences in total vascular compliance, which is the inverse of the slope of this curve and is an index of total venous compliance, between Goldblatt and control groups at any time-period studied. These results suggest that decreased venous capacity observed in chronic hypertensive rats may be a secondary hemodynamic state and may not be related to decreased venous compliance.
Abstract 146: Disruption of Nox2 and TNFRp55/p75 Eliminates Anisomycin-Induced Preconditioning Effect in the Heart
Authors: Ting C Zhao, Ling Zhang, Tai-Liang Guo
Journal: Circulation Research (2012)

Background: Transient activation of p38 through anisomycin is demonstrated to precondition the heart against myocardial injury. However, it remains unknown whether specific TNF-α receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH-oxidase are involved in this event. Objective: We sought to investigate whether the genetic disruption of TNFRp55/p75 and Nox2 eliminates cardioprotection elicited by anisomycin and whether p38-dependent activation of Nox2 stimulates TNFR to ultimately achieve protective effects. Methods: Adult wild type and p55/p75 -/- and Nox2 -/- mice received intraperitoneal injections of anisomycin (0.1mg/kg), a potent activator of p38. The hearts were subjected to 30 min myocardial ischemia /30 min reperfusion in the Langendorff perused heart after twenty four hours. Left ventricular function was measured and infarct size was determined by triphenyltetrazolium chloride. Myocardial TNF-α protein, Nox2 and superoxides releases were detected. Gel kinase assay was employed to detect the effect of p38 on Nox2 phosphorylation. Results: Activation of p38 through anisomycin produces marked improvements in the recovery of left ventricular end diastolic pressure, rate pressure products, and the reduction of myocardial infarction, which were completely abrogated by disruption of Nox2 and TNFR p55/p75. Genetic disruption of Nox2 and TNFR p55/p75 abolished the effect of anisomycin-induced reduction of infarct size. Ansiomycin induced the production of TNFα, which was abrogated in Nox2 -/- mice. Notably, activation of p38 resulted in the phosphorylation of Nox2. Conclusion: Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection.
Safety and Efficacy of Addition of Pegylated Interferon alpha2b to Standard Dose Dasatinib in Newly Diagnosed Chronic Phase CML Patients
Authors: Henrik Hjorth-Hansen, Jesper Stentoft, Johan Richter, Perttu Koskenvesa, Arta Dreimane, Kimmo Porkka, Tobias Gedde-Dahl, Bjorn Gjertsen, Franz X. Gruber, Martin Hoglund, Anna Lubking, Kristina Myhr-Eriksson, Berit Markevärn, Hanne Vestergaard, Ole Weis Bjerrum, Leif Stenke, Satu Mustjoki, Ulla Stromberg
Journal: Blood (2015)
S85 Reduction of CD68 macrophages causes gender specific spontaneous pulmonary arterial hypertension in mice
Authors: A Zawia, N Arnold, A Braithwaite, J Pickworth, K Hopkinson, J Iremonger, G Miller, A Lawrie
Journal: Thorax (2016)

<h3>Introduction</h3> Macrophages are proposed to play an important regulatory role in the pathogenesis of pulmonary arterial hypertension (PAH) as excessive infiltration detected around vascular lesions in patients and animal models. The exact ‘causal’ role for macrophages, and whether their presence or absence is required for the vascular remodelling seen in PAH remains unclear. <h3>Objectives</h3> Using a novel inducible macrophage depletion model (<i>MacLow</i> mouse) we aimed to determine the role of macrophages in pulmonary arterial remodelling associated with PAH. <h3>Methods</h3> Macrophage depletion was induced in <i>MacLow</i> mice by administration of doxycycline, where macrophage-specific induction of the cytotoxic diphtheria toxin A chain (DTA) is driven by the CD68 promoter. Mice were phenotyped for PAH by echocardiography, closed chest cardiac catheterization and immunohistochemistry (IHC) after 6 weeks. To investigate the origin of the effector cells, male chimeric mice were generated, and the disease stimulated by inducing macrophage ablation with doxycycline. Furthermore, to study gender-specificity of the disease phenotype, <i>MacLow</i> mixed gender chimeric mice were produced, and macrophage ablation induced as previous. <h3>Results</h3> Interestingly male but not female <i>MacLow</i> mice developed a PAH phenotype compared to controls (RVSP of 66.1 mmHg vs 24.5 mmHg, p &lt; 0.0001, n = 5–8), associated with increased right ventricular Hypertrophy (RVH 0.264 vs 0.226, p &lt; 0.001, n = 8) and pulmonary vascular remodelling. IHC analysis of diseased lungs demonstrated increased iNOS- |CD206+ |F4/80+ macrophages suggesting a M2-like macrophage population drive the PAH phenotype in these mice. The bone marrow transplant studies shows that bone marrow (BM) derived cells contribute in the development of the disease phenotype as wild type BM cells attenuate disease progression. Moreover, female BM transplanted into male mice alleviate but does not protect them from developing PAH. <h3>Conclusion</h3> Development of PAH in male <i>MacLow</i> mice suggests that macrophages play a causal role in pulmonary vascular remodelling. Results suggest that the phenotype is driven by lung resident M2- like macrophages with a contribution from bone marrow derived cells. A study to examine the probable protective effect of Oestrogen is now underway to further investigate the implication of gender difference in the incidence of PAH in this model.
P248 Patient eligibility for anti-fibrotic therapy in idiopathic pulmonary fibrosis can be altered by use of different sets of reference values for calculation of fvc percent predicted
Authors: K Ward, L Spurr, NR Goldman, GA Margaritopoulos, M Kokosi, E Renzoni, F Chua, TM Maher, S Ward, AU Wells
Journal: Thorax (2016)

<h3>Introduction</h3> Antifibrotic drugs for idiopathic pulmonary fibrosis (IPF) patients in England and Scotland are only available to those with FVC percent predicted (FVC%pred) less than or equal to 80%. The prescribing guidance does not state which reference values should be used. <h3>Aims</h3> To find out if the use of different sets of reference values affects the numbers of patients with FVC%pred greater than and less than 80%. To find out which reference equations were in use at UK centres prescribing antifibrotics for IPF in April 2016. <h3>Methods</h3> We searched databases for patients diagnosed with IPF at our interstitial lung disease (ILD) unit from 1/1/2010 to 31/12/2015. We calculated FVC%pred using three different sets of reference values (ECSC, GLI or NHANES). The chief respiratory physiologist in each ILD centre in England was contacted and asked which reference values they used to calculate FVC%pred. In Scotland, four hospitals with an ILD MDT were contacted and asked the same. McNemar tests were used to compare the proportion of patients eligible for antifibrotic prescription when FVC%pred was calculated by ECSC or either NHANES or GLI. <h3>Results</h3> See Table 1. We identified 671 unique patients: after exclusions, 528 had complete data. There was a higher proportion of patients calculated to have an FVC%pred &gt;80% (ineligible for antifibrotics) using ECSC than GLI: Chi-square 22.0, 1df, P&lt;0.0001. The difference in proportions was greater when ECSC was compared to NHANES: Chi square 33.03, 1df, P &lt; 0.0001. Of 30 patients with ECSC FVC%pred 80–85%, 27 [90%: 95% CI: 79–100%) had their FVC%pred fall to &lt;80% when recalculated with NHANES. 18 of 20 ILD centres in England were using ECSC to calculate FVC%pred; others used GLI (n = 1) and Falaschetti (n = 1). All four Scottish centres were using ECSC. <h3>Discussion</h3> Many patients with ECSC FVC%pred too high for antifibrotics fall into the eligible range when NHANES, the set of reference values used in the ASCEND pirfenidone trial, or GLI, as recommended by the UK Association for Respiratory Technology and Physiology(ARTP) are used. <h3>Conclusions</h3> We urge physicians and physiologists to ensure that reference values used to calculate FVC%pred are cited in lung function reports. Those choosing reference values must be aware of implications for patients.