tbuckley/cabot-search huggingface dataset:
Recurrent Oncogenic Mutations in CCND3 in Aggressive Lymphomas
Authors: Roland Schmitz, Sameer Jhavar, Wenming Xiao, Xuelu Liu, John Powell, George W. Wright, Wing C. Chan, Elaine S. Jaffe, Randy D. Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M. Rimsza, Louis M. Staudt
Journal: Blood (2011)
Targeting Thrombomodulin to Endothelial ICAM-1 Rather Than PECAM-1 Allows Partnering with the Endothelial Protein C Receptor and Enhances Protection of Endothelial Barrier Function
Authors: Colin F Greineder, Sergei Zaytsev, Blaine Zern, Ann Marie Chacko, Vladimir R Muzykantov
Journal: Blood (2012)
Exercise medicine education should be expanded
Authors: Michael J Joyner, Fabian Sanchis-Gomar, Alejandro Lucia
Journal: British Journal of Sports Medicine (2016)

Second to tobacco control, a case can be made that physical activity and/or structured exercise is the best medicine for many of most prevalent non-communicable diseases in the developed world.1 This is especially true for metabolic and cardiovascular disease (CVD), in a preventive and therapeutic context. Although still limited in quantity, currently available evidence based on randomised trials indicates that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of CVD, rehabilitation after stroke, treatment of heart failure and prevention of diabetes.2 A recent meta-analysis of trials investigating the effect of exercise on CVD risk factors in patients with the metabolic syndrome reported a 10% drop-out from the exercise programmes,3 whereas those taking medications for CVD prevention are more likely to discontinue medication compared with placebo or one drug component (20% vs 14%).4 Exercise training is associated with an overall decline in glycosylated haemoglobin (HbA1c) levels,5 which …
The Prevalence of Antibiotic-Resistant <i>Staphylococcus aureus</i> Nasal Carriage among Industrial Hog Operation Workers, Community Residents, and Children Living in Their Households: North Carolina, USA
Authors: Sarah M. Hatcher, Sarah M. Rhodes, Jill R. Stewart, Ellen Silbergeld, Nora Pisanic, Jesper Larsen, Sharon Jiang, Amanda Krosche, Devon Hall, Karen C. Carroll, Christopher D. Heaney
Journal: Environmental Health Perspectives (2016)

Antibiotic use in industrial hog operations (IHOs) can support the emergence of antibiotic-resistant (ABR) Staphylococcus aureus. The extent of ABR S. aureus exposure in IHO workers and children living in their households remains unclear.We investigated ABR S. aureus nasal carriage prevalence among adults with versus without occupational exposure to IHOs and among children living in their households.In total, 198 IHO worker-child household pairs and 202 community referent (CR) adult-child household pairs completed a questionnaire and provided a nasal swab which was analyzed for S. aureus, methicillin-resistant S. aureus (MRSA), multidrug-resistant S. aureus (MDRSA), absence of scn (putative marker of livestock association), and spa type.S. aureus nasal carriage prevalence was higher among IHO (53%) compared with CR (31%) adults [adjusted prevalence ratio (aPR): 1.40; 95% confidence interval (CI): 1.07, 1.83], but MRSA nasal carriage prevalence was uncommon (2-3%) in IHO and CR adults. MDRSA nasal carriage prevalence was similar among IHO workers and CR adults (12% vs. 8%; aPR: 1.14; 95% CI: 0.56, 2.29). Nasal carriage prevalence was higher among IHO compared with CR children for S. aureus (49% vs. 31%; aPR: 1.50; 95% CI: 1.13, 1.99), MRSA (14% vs. 6%; aPR: 2.37; 95% CI: 1.14, 4.92), and MDRSA (23% vs. 8%; aPR: 2.64; 95% CI: 1.47, 4.75). We also found suggestive evidence of a higher prevalence of S. aureus, MRSA, and MDRSA among children living with an IHO worker who did versus did not report taking personal protective equipment (PPE) home from the IHO. Livestock-associated S. aureus nasal carriage predominated among IHO workers.Our findings support the importance of further research on the prevalence and potential sources of exposure to ABR S. aureus among children living with IHO workers.
Assessment of Rabbit Antithymocyte Globulin (rATG) Dose-Intensity in Patients with Hematological Malignancies Undergoing Allogeneic Stem Cell Transplantation (ASCT) Following Reduced Intensity Conditioning (RIC) with Fludarabine, Busulfan and rATG (FBA)
Authors: Mehdi Hamadani, William Blum, Don Benson, Kristie A Blum, Pierluigi Porcu, Patrick Elder, David Krugh, Thomas Bechtel, Leslie Andritsos, Ramiro Garzon, Sam Penza, Thomas S. Lin, Steven Devine
Journal: Blood (2008)
Divergent effects of tamoxifen and trilostane in activating protein–1 gene transcription and progesterone receptor expression in breast cancer
Authors: S. Barker, H. R. Glover, S. D. M. Malouitre, J. R. Puddefoot, G. P. Vinson
Journal: Journal of Clinical Oncology (2004)

647 Background: Activating protein-1 (AP1) elements in gene promoters are pivotal in growth factor mediated cell survival pathways in breast cancer. Selective estrogen receptor modulators are known to alter estrogen receptor (ER) conformation giving rise to differential gene activation through estrogen response elements (EREs) and AP1 elements. Trilostane is an effective treatment in advanced breast cancer. Trilostane also has a novel allosteric effect on ER that leads to reduced binding to EREs and inhibition of breast cancer cell proliferation. We compare the effects of trilostane and tamoxifen on an AP1 reporter system and progesterone receptor (PgR) gene expression in vitro. Methods: An AP1-reporter plasmid was transfected into MDA-MB-231 breast cancer cells transiently co-transfected with plasmids encoding ER beta or ER alpha and assayed by luminescence after 72h treatment with trilostane, or tamoxifen in the presence of the AP1 activators epidermal growth factor (EGF) and 17-beta estradiol (E2). Expression of the AP1-dependent PgR gene was assayed by RT-PCR in MCF-7 cells after similar treatments. Results: A 3-fold increase in AP1 activity was observed in MDA-MB-231 ER alpha-transfected cells in response to E2 and EGF. This was blocked by trilostane. Tamoxifen had no effect. ER beta-transfected cells showed similar responses. In addition, trilostane reduced E2-stimulated PgR mRNA levels while tamoxifen did not. 4-hydroxy tamoxifen, a potent metabolite of tamoxifen, augmented E2-stimulated PgR expression in these cells. Conclusions: The contrasting effects of tamoxifen and trilostane on the AP1-reporter assay and PgR expression suggest different mechanisms that involve conformational changes in ER. Trilostane's unique profile of action could explain the proven benefit to breast cancer patients who have become refractory to tamoxifen therapy, especially as their tumors evolve from an ERE- to an AP1-dependent phenotype. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bioenvision Inc.
Induced Pluripotent Stem Cell Model of Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity
Authors: Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A. T. Elliott, Dan Li, Fabian Grubert, Caiyun G. Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C. Wu, Michael P. Snyder, Marlene Rabinovitch
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies.Objectives: Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns that differed from those in unused donor cells. We then investigated whether endothelial cells differentiated from pluripotent cells could serve as surrogates to test emerging therapies.Methods: Functional changes assessed included adhesion, migration, tube formation, and propensity to apoptosis. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and its target, collagen IV, signaling of the phosphorylated form of the mothers against decapentaplegic proteins (pSMAD1/5), and transcriptomic profiles were also analyzed.Measurements and Main Results: Native pulmonary arterial and induced pluripotent stem cell–derived endothelial cells from patients with idiopathic and heritable pulmonary arterial hypertension compared with control subjects showed a similar reduction in adhesion, migration, survival, and tube formation, and decreased BMPR2 and downstream signaling and collagen IV expression. Transcriptomic profiling revealed high kisspeptin 1 (KISS1) related to reduced migration and low carboxylesterase 1 (CES1), to impaired survival in patient cells. A beneficial angiogenic response to potential therapies, FK506 and Elafin, was related to reduced slit guidance ligand 3 (SLIT3), an antimigratory factor.Conclusions: Despite the site of disease in the lung, our study indicates that induced pluripotent stem cell–derived endothelial cells are useful surrogates to uncover novel features related to disease mechanisms and to better match patients to therapies.
Abstract PR14: Epidermal neoplasms bypass immune evasion requirements via niche occupancy
Authors: Brad Kubick, Dennis Roop
Journal: Cancer Research (2016)

Abstract Anti-tumor immune effectors exert selective pressure against transformed clones, ultimately permitting only mutation cascades that are either non-immunogenic or include immune-evasive adaptations. This evolutionary process often includes an equilibrium phase during which immunogenic transformed cells are prevented from outgrowth by the immune system without being eliminated. In most cases, escape from this state requires loss of antigen presentation and consequent loss of immunogenicity. To characterize this pre-outgrowth phase of cancer-immune interaction and test the efficacy of interventions during dormancy, we assembled a genetically-engineered mouse model (GEMM) of inducible, Kras-driven carcinogenesis coupled to a fluorescent reporter. Early characterization of this model revealed a confounding artificial tolerance mechanism that renders inducible alleles automatically non-immunogenic in autochthonous settings. To circumvent this tolerance, we transplant dissociated epidermal keratinocytes from the GEMM onto recipient animals that do not carry the inducible mutant Kras allele. This transplant step also enables the use recipient animals carrying various immune deficiencies. After graft healing, transformation is induced and the grafts are imaged repeatedly over time via intravital confocal microscopy. In immunocompromised recipients, transformation initiates the rapid growth of labeled cells and subsequent tumor formation. In immunocompetent cohorts, tumor formation does not occur. Instead, we observe establishment of a long-term equilibrium phase characterized by cyclic growth and regression of labeled clones originating exclusively from hair follicles, suggesting that the immune privilege of this stem cell niche provides a safe harbor for transformed cells. Surprisingly, the architecture of the normal tissue defines a protected reservoir for the survival of transformed cells, a fate that usually requires cell-intrinsic immune-evasive adaptations. This provides a mechanism by which a single source of anti-tumor activity could produce the observed biphasic nature of cancer-immune interaction, including both elimination of some clones and immune-mediated dormancy of others. Most importantly, we have identified a novel pre-malignant, immune-controlled state that may represent a vulnerable target population for rational cancer prevention strategies. Citation Format: Brad Kubick, Dennis Roop. Epidermal neoplasms bypass immune evasion requirements via niche occupancy. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR14.
BT062, a CD138-Specific Immunoconjugate, Demonstrates Superior In Vivo Anti-Myeloma Efficacy In Combination with Lenalidomide or Bortezomib
Authors: Chantal Zuber, Benjamin Daelken, Silke Aigner, Thomas Haeder, Olga Ab, Kathleen Whiteman, Teru Hideshima, Robert J Lutz, Frank Osterroth, Christoph Uherek
Journal: Blood (2010)
Making Functional Endothelial Progenitors: Humanized Large-Scale Animal Serum-Free Propagated Adult Blood-Derived Endothelial Colony-Forming Cells Assemble Stable Perfused Vessels in Vivo.
Authors: Andreas Reinisch, Nicole A Hofmann, Anna C Obenauf, Karl Kashofer, Eva Rohde, Katharina Schallmoser, Daniela Thaler, Margareta Frühwirth, Werner Linkesch, Michael R Speicher, Dirk Strunk
Journal: Blood (2008)
Melphalan and Dexamethasone Is Less Effective for Patients with Immunoglobulin Light Chain Amyloidosis (AL) with High Bone Marrow Plasmacytosis.
Authors: Nelson Leung, Heidi D Gunderson, Tow S Tan, Angela Dispenzieri, Morie A Gertz, Steven R Zeldenrust, Martha Q Lacy, Francis K Buadi, Suzanne R. Hayman, Shaji Kumar
Journal: Blood (2008)
Aspirin Resistance - A Comparison of Platelet Functions and 11-Dehydro Thromboxane B2 and 8-epi Prostaglandin F2α Plasma Concentration.
Authors: Krystyna Zawilska, Marcin Zytkiewicz, Ewelina Hanszke, Liwia Gielwanowska, Piotr Psuja, Zofia Turowiecka, Irmina Gaik, Maria Zozulinska, Malgorzata Duszynska
Journal: Blood (2005)
Cytogenetic Characteristic of Mesenchymal and Hematopoetic Progenitor Cells in Myelodysplastic Syndromes and Acute Myeloid Leukemias with Myelodysplasia-Related Changes
Authors: Maria Pimenova, Alina V Kokhno, Elena V Domracheva, Yulia Malceva, Lubov Shishigina, Maria Konnova, Nina I. Drize, Tatyana Manakova, Elena Parovichnikova, Valeriy G Savchenko
Journal: Blood (2012)
The nuclear pore protein Nup153 associates with chromatin and regulates cardiac gene expression in dystrophic<i>mdx</i>hearts
Authors: Simona Nanni, Agnese Re, Cristian Ripoli, Aoife Gowran, Patrizia Nigro, Domenico D’Amario, Antonio Amodeo, Filippo Crea, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Claudia Colussi
Journal: Cardiovascular Research (2016)

Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmd mdx /J).Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls. Accordingly, lysine acetyl transferase (KAT) activity associated with Nup153 was higher in mdx hearts paralleling increased binding with the lysine acetylases P300/CBP-associated factor (PCAF) and p300. Interestingly, Nup153 silencing in mdx organotypic heart tissue slices caused a reduction in PCAF- and p300-specific activities. Remarkably, the level of nitric oxide (NO), which is reduced in mdx mice, was important for KAT-dependent regulation of Nup153. In fact, treatment of mdx heart tissue with an NO donor or the KAT inhibitor anacardic acid normalized Nup153 protein expression. Nup153 was recruited to chromatin and regulated the transcription of genes involved in cardiac remodelling, including the actin-binding protein nexilin. Accordingly, nexilin protein expression was abrogated by Nup153 silencing in mdx organotypic cultures. Electrophysiological and molecular experiments revealed that Nup153 overexpression in normal cardiomyocytes increases Ca v 1.2 calcium channel expression and function. Alterations in Nup153 protein expression and intracellular localization were also found in dystrophic cardiomyocytes derived from patient-specific induced pluripotent stem cells. Importantly, Nup153 up-regulation and increased acetylation were also found in the heart of Duchenne muscular dystrophy patients.Our data indicate that Nup153 is an epigenetic regulator which, upon altered NO signalling, mediates the activation of genes potentially associated with early dystrophic cardiac remodelling.
GW26-e4692 A multi-center study on the therapeutic status of patients with acute myocardial infarction in Wuxi City, China
Authors: Suxia Guo, Chengjian Yang, Yijia Tao, Feng Chen, Wei Su, Ruolong Zheng, Song Yang, Xudong Li, Jingkai Chen, Zhenyu Yang
Journal: Journal of the American College of Cardiology (2015)
Obesity is more closely related with hepatic steatosis and fibrosis measured by transient elastography than metabolic health status
Authors: Ji Hye Huh, Kwang Joon Kim, Seung Up Kim, Seung Hwan Han, Kwang-Hyub Han, Bong-Soo Cha, Choon Hee Chung, Byung-Wan Lee
Journal: Metabolism (2016)
Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling
Authors: Isabelle Mondor, Audrey Jorquera, Cynthia Sene, Sahil Adriouch, Ralf Heinrich Adams, Bin Zhou, Stephan Wienert, Frederick Klauschen, Marc Bajénoff
Journal: Immunity (2016)
Treatment of Primary Immune Thrombocytopenia with Thrombopoietin Receptor Agonists: Effect On Platelet Function and Plasma Thrombin Generation
Authors: Ihosvany Fernández Bello, Victor Jimenez Yuste, Mayte Álvarez Román, Monica Martin Salces, Miguel Canales, Nora V. Butta
Journal: Blood (2012)
P0799 : The Pharmacokinetics of beclabuvir (BMS-791325) when administered in combination with daclatasvir and asunaprevir in treatment-naive patients with or without cirrhosis infected with HCV genotype 1
Authors: B. He, K. Sims, E. Chung, W.-L. Luo, J. Pursley, M. Wind-Rotolo, F. LaCreta, R. Bertz, M. AbuTarif
Journal: Journal of Hepatology (2015)
Abstract C39: High-content screening to capture tumor dynamics in response to microenvironmental perturbations
Authors: Colleen M. Garvey, Oscar Chen, Jasmine Foo, Shannon M. Mumenthaler
Journal: Cancer Research (2016)

Abstract Tumor populations are in constant flux as a result of dynamic pressures of their surrounding microenvironment. Measuring the phenotypic response of multiple cell types exposed to physiological relevant tumor conditions has been a challenge due to the heterogenous nature of the tumor microenvironment. Further, traditional cell biology assays for assessing cell viability do not allow for additional downstream analyses and use surrogate measures for cell number, which may fail to provide a complete picture of cellular events. Here, we present a method to utilize high-content screening to generate quantitative, robust data sets characterizing cellular phenotypic responses (i.e. birth, death, morphology) of tumor cells to co-occurring perturbations of drug, oxygen, glucose, ECM stiffness, and stromal cell co-culture. Using an Operetta high-content imaging platform, we are able to perform multiple analyses on the same experimental setup to quantitatively assess the evolutionary dynamics of heterogenous cell populations under multiple environmental perturbations. We are able to differentiate between the effect of microenvironmental conditions on a decrease in cell birth versus increase in cell death, which has significant implications for predicting tumor growth kinetics and drug treatment response. We applied this platform to analyze isogenic lung tumor cells that are either sensitive or resistant to erlotinib, a commonly used tyrosine receptor kinase inhibitor in the treatment of lung cancer. We identified specific microenvironmental contexts where the resistant populations have a fitness advantage over the sensitive population, irrespective of the resistance mechanism. Furthermore, our experimental workflow allows us to capture and quantify cell morphology, an additional measure for overall cell health. We observed significant shifts in specific cell morphological parameters in response to alterations in tumor microenviromental conditions such as low oxygen and increased drug concentration. This novel application of a high-content screening platform allows for the quantification of multiple cellular phenotypes in response to over a hundred different microenvironmental contexts, thus providing deeper insight into the effect of tumor microenvironmental heterogeneity on evolving tumor cell populations. Citation Format: Colleen M. Garvey, Oscar Chen, Jasmine Foo, Shannon M. Mumenthaler. High-content screening to capture tumor dynamics in response to microenvironmental perturbations. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C39.
Multi-Center Phase II Study of Perifosine (KRX-0401) Alone and in Combination with Dexamethasone (dex) for Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Promising Activity as Combination Therapy with Manageable Toxicity.
Authors: Paul Richardson, S. Lonial, A. Jakubowiak, A. Krishnan, J. Wolf, J. Densmore, S. Singhal, I. Ghobrial, J. Stephenson, J. Mehta, K. Colson, D. Francis, T. Kendall, N. Obadike, K. Sullivan, J. Martin, T. Hideshima, L. Lai, P. Sportelli, L. Gardner, R. Birch, I.C. Henderson, K. Anderson
Journal: Blood (2007)
Response to Comment on Ferrannini et al. Diabetes Care 2016;39:1108–1114. Comment on Mudaliar et al. Diabetes Care 2016;39:1115–1122
Authors: Ele Ferrannini, Michael Mark, Eric Mayoux
Journal: Diabetes Care (2016)

Ceriello et al. (1) argue that the cardiovascular benefit documented in the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study may be due to direct actions of glucagon on myocardial function. We regard this hypothesis as unlikely. Because of the widespread tissue distribution of its receptors, glucagon has been credited with exerting cardiovascular and renal actions in addition to its classical effects on liver and brain. In early studies of heart–lung preparations, glucagon increased heart rate and contractility in a dose-dependent manner. In intact animals, glucagon increased splanchnic and renal blood flow and glomerular filtration rate; reduced peripheral vascular resistance and enhanced natriuresis and kaliuresis were …