tbuckley/cabot-search huggingface dataset:
Lung tissue gene-expression signature for the ageing lung in COPD
Authors: Maaike de Vries, Alen Faiz, Roy R Woldhuis, Dirkje S Postma, Tristan V de Jong, Don D Sin, Yohan Bossé, David C Nickle, Victor Guryev, Wim Timens, Maarten van den Berge, Corry-Anke Brandsma
Journal: Thorax (2017)

Introduction COPD is a chronic, progressive, inflammatory disease of the lungs and the third leading cause of death worldwide. The current knowledge of the pathophysiology of COPD is limited and novel insights in underlying disease mechanisms are urgently needed. Since there are clear parallels between ageing and COPD, we investigated genes underlying lung ageing in general and abnormal lung ageing in COPD. Methods Whole genome mRNA profiling was performed on lung tissue samples (n=1197) and differential gene expression with increasing age was analysed using an adjusted linear regression model. Subsequent pathway analysis was performed using GeneNetwork and the gene-expression signature was compared with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of patients with COPD (n=311) and non-COPD controls (n=270), we performed an interaction analysis between age and COPD to identify genes differentially expressed with age in COPD compared with controls, followed by gene set enrichment pathway analysis. Results We identified a strong gene-expression signature for lung ageing with 3509 differentially expressed genes, of which 33.5% were found nominal significant in the GTEx project. Interestingly, we found EDA2R as a strong candidate gene for lung ageing. The age*COPD interaction analysis revealed 69 genes significantly differentially expressed with age between COPD and controls. Conclusions Our study indicates that processes related to lung development, cell-cell contacts, calcium signalling and immune responses are involved in lung ageing in general. Pathways related to extracellular matrix, mammalian target of rapamycin signalling, splicing of introns and exons and the ribosome complex are proposed to be involved in abnormal lung ageing in COPD.
Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy
Authors: Leonela Amoasii, Chengzu Long, Hui Li, Alex A. Mireault, John M. Shelton, Efrain Sanchez-Ortiz, John R. McAnally, Samadrita Bhattacharyya, Florian Schmidt, Dirk Grimm, Stephen D. Hauschka, Rhonda Bassel-Duby, Eric N. Olson
Journal: Science Translational Medicine (2017)

Single-cut correction of a dystrophin gene mutation with CRISPR/Cas9 restored dystrophin expression in skeletal and cardiac muscles in a mouse model of Duchenne muscular dystrophy.
Abstract B14: Injection of therapeutic stem cells expressing cytosine deaminase and interferon-beta resulted in the inhibition of K562 human chronic myeloid leukemia cells in a xenograft model
Authors: Geon-Tae Park, Kyung-Chul Choi
Journal: Cancer Research (2017)

Abstract Gene-directed enzyme/prodrug therapies have been found to be more advantageous compared to conventional cancer treatment method. One of these, a cytosine deaminase (CD)/5-fluorocytosine (5-FC) system, is known to induce apoptosis of cancer cells by converting 5-FC, a prodrug, to its metabolically active form, 5-fluorouracil. In this study, human neural stem cells (hNSCs) derived enzyme/prodrug therapy was used to treat leukemia. The parental hNSCs, HB1.F3, were engineered to express E. coli CD and/or human interferon-β. To manufacture animal models xenografted with leukemia, K-562 cells (1×106) were mixed with Matrigel (BD Biosciences, Bedford, MA, USA) at 1:1 volume ratio of Matrigel to PBS in 100 μl and injected subcutaneously (s.c.) into the back of athymic nude mice. This animal study was performed for 24 days after hNSCs injections. When tumor volume reached 500 mm3, CM-Dil pre-labeled hNSCs (4 x 106 cells per mouse) were injected subcutaneously adjacent to the tumor mass. Another group, CM-dil pre-labeled hNSCs (4 x 106 cells per mouse) was injected intravenously. hNSCs were injected on the first day of each week. Two days after the injection of hNSCs, all mice received i.p. injections of 5-FC (500 mg/kg/day in 100 μl PBS) every day for 24 days. At 24 h after the last 5-FC treatment, the mice were euthanized and tumor masses were harvested for molecular analysis. In a xenografted mouse model administered with hNSCs intravenously or subcutaneously, hNSC significantly inhibits the growth of tumor mass and extends survival date in the presence of a prodrug. In addition, HB1.F3.CD.IFN-β treatment group showed more antitumor effect compared with HB1.F3.CD treatment group, indicating that IFN- β may have a synergistic effect for directly killing leukemia tumors. The present results represent that engineered hNSCs and prodrug treatment inhibited the proliferation of leukemia. These results suggest that gene therapy employing genetically engineered stem cells expressing CD and IFN-β may be effective for treating leukemia. Note: This abstract was not presented at the conference. Citation Format: Geon-Tae Park, Kyung-Chul Choi. Injection of therapeutic stem cells expressing cytosine deaminase and interferon-beta resulted in the inhibition of K562 human chronic myeloid leukemia cells in a xenograft model [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B14.
Blockade of VEGF-A prevents mobilization and recruitment of endothelial progenitor cells (EPCs) to the tumor vasculature
Authors: Hans-Peter Gerber, Ajay K. Malik, Megan Baldwin, Kathleen Daly, Germaine Fuh, Napoleone Ferrara
Journal: Cancer Research (2005)

5492  Proliferation of endothelial cells (ECs) and recruitment of bone marrow derived endothelial progenitor cells (EPCs) are two distinct processes contributing to tumor angiogenesis and thus either pathway may compensate during selective inhibition of the other. Here we investigate the role of VEGF-A, a potent mitogen for endothelial cells, in the recruitment of EPCs to the tumor vasculature. We employed a monoclonal antibody which selectively neutralize VEGF-A (G6-23) and compared their pharmacological effects with a soluble VEGFR-1 receptor-IgG chimera [mFlt(1-3)-IgG], which neutralizes VEGF-A, -B and PlGF. On day 4 post tumor implantation, both compounds abolished EPC recruitment to the tumor vasculature to similar extends and reduced the numbers of circulatory endothelial progenitor cells (CEPs) to background levels. However, despite the reduction in both, EPCs and CEPs, tumor angiogenesis and growth eventually resumed during later stages of anti-VEGF treatment. Our findings demonstrate that VEGF-A is a key regulator of EPC recruitment to tumor vasculature and that endogenous levels of PlGF and VEGF-B failed to compensate when VEGF-A was neutralized. Furthermore, EPCs and endogenous levels of VEGF-A, B and PlGF may not contribute significantly to the “escape from anti-VEGF” mechanism identified in this model.
Survival outcomes across ethnicities in triple-negative breast cancer.
Authors: Moira Katherine Rushton, Tinghua Zhang, Xinni Song
Journal: Journal of Clinical Oncology (2014)

1113 Background: Triple negative breast cancer (TNBC) is a heterogeneous disease characterized by the lack of receptor expression (ER, PR, and HER2/neu negative). Amongst breast cancer types TNBC has a less favourable prognosis. There is a higher incidence of TNBC in African-American women than Caucasian women. What has not been clearly elucidated is whether survival outcomes are different among women with TNBC from different ethnic background. Methods: The objective of our study was to determine if significant differences exist in overall survival (OS) of TNBC patients across various ethnicities, including but not limited to Caucasian, African-American, and Asian. Using population data a multivariate analysis was done to take into account age, stage, and treatments received. Results: Using data from SEER database 6,227 cases of TNBC across all ethnicities were reported in 2010. At year one of follow-up, mortality rate was 2.6% (n=162) Race was found to be a potential predictor of breast cancer mortality with a mortality rate of 3.13% in American Indian/Alaskan Native and Pacific Islander patients; 2.75% in black patients; 2.6% in white patients. When adjusted for age and stage at time of diagnosis in multivariate analysis, there was no significant difference in OS for any ethnicity when compared to Caucasian patients. Specifically black TNBC patients had an OR 1.089 (p=0.69) and Asian patients OR 1.084 (p=0.87). Conclusions: While there was some suggestion that there was a higher one year breast cancer mortality rate in some populations, in multivariate analysis this was not a significant finding. Longer follow-up is needed before conclusions can be made about differences between ethnic groups. We are planning to review other large population databases to gather a greater pool of data to answer this question. Determining if there are certain populations do worse will inform the medical oncology community of an area to focus greater study to determine how to optimize therapies for that patient group.
Chimeric Antigen Receptor-Engineered Human Gamma Delta T Cells: Enhanced Cytotoxicity with Retention of Cross Presentation
Authors: Anna Capsomidis, Gabriel Benthall, Heleen H. Van Acker, Jonathan Fisher, Anne M. Kramer, Zarah Abeln, Yvonne Majani, Talia Gileadi, Rebecca Wallace, Kenth Gustafsson, Barry Flutter, John Anderson
Journal: Molecular Therapy (2017)

Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response. Using a GD2-targeting CAR as a model system, we showed that γδT cells of both Vδ1 and Vδ2 subsets could be expanded and transduced to sufficient numbers for clinical studies. The CAR added to the cells' innate cytotoxicity by enhancing GD2-specific killing of GD2-expressing cancer cell lines. Migration toward tumor cells in vitro was not impaired by the presence of the CAR. Expanded CAR-transduced Vδ2 cells retained the ability to take up tumor antigens and cross presented the processed peptide to responder alpha beta T (αβT) lymphocytes. γδ CAR-T cell products show promise for evaluation in clinical studies of solid tumors.
PSMA brings new flavors to PI3K signaling: A role for glutamate in prostate cancer
Authors: Lavinia Palamiuc, Brooke M. Emerling
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Kaittanis et al. (https://doi.org/10.1084/jem.20171052) report a new signaling role for prostate-specific membrane antigen (PSMA), providing a mechanistic link between two major oncogenic pathways, as well as promising therapeutic implications for the diagnosis and treatment of prostate cancer.
Length of Stay After Overlapping Surgery—Reply
Authors: Edward H. Livingston, Michelle M. Mello
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Rare mutations provide unique insight into oncogenic potential of STAT transcription factors
Authors: Lisa N. Heppler, David A. Frank
Journal: Journal of Clinical Investigation (2017)

The inappropriate activation of transcription factors, including STATs, is known to promote tumor initiation and progression. The most common mechanisms of misregulation lead to constitutive activation of WT STATs. However, the recent discovery of rare STAT mutations in hematopoietic malignancies suggests that STAT mutants may be oncogenic. In this issue of the JCI, Pham et al. use a transgenic mouse model to demonstrate that STAT5BN642H is sufficient for the development of T cell neoplasia. This study, along with other studies of constitutively active STAT mutants, provides insight into the pathogenesis and treatment of STAT5-driven cancer.
A2AR Adenosine Signaling Suppresses Natural Killer Cell Maturation in the Tumor Microenvironment
Authors: Arabella Young, Shin Foong Ngiow, Yulong Gao, Ann-Marie Patch, Deborah S. Barkauskas, Meriem Messaoudene, Gene Lin, Jerome D. Coudert, Kimberley A. Stannard, Laurence Zitvogel, Mariapia A. Degli-Esposti, Eric Vivier, Nicola Waddell, Joel Linden, Nicholas D. Huntington, Fernando Souza-Fonseca-Guimaraes, Mark J. Smyth
Journal: Cancer Research (2017)

Extracellular adenosine is a key immunosuppressive metabolite that restricts activation of cytotoxic lymphocytes and impairs antitumor immune responses. Here, we show that engagement of A2A adenosine receptor (A2AR) acts as a checkpoint that limits the maturation of natural killer (NK) cells. Both global and NK-cell-specific conditional deletion of A2AR enhanced proportions of terminally mature NK cells at homeostasis, following reconstitution, and in the tumor microenvironment. Notably, A2AR-deficient, terminally mature NK cells retained proliferative capacity and exhibited heightened reconstitution in competitive transfer assays. Moreover, targeting A2AR specifically on NK cells also improved tumor control and delayed tumor initiation. Taken together, our results establish A2AR-mediated adenosine signaling as an intrinsic negative regulator of NK-cell maturation and antitumor immune responses. On the basis of these findings, we propose that administering A2AR antagonists concurrently with NK cell-based therapies may heighten therapeutic benefits by augmenting NK cell-mediated antitumor immunity.Significance: Ablating adenosine signaling is found to promote natural killer cell maturation and antitumor immunity and reduce tumor growth. Cancer Res; 78(4); 1003-16. ©2017 AACR.
Ocular Therapeutics: Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation (Adv. Healthcare Mater. 23/2017)
Authors: Michelle L. Ratay, Elena Bellotti, Riccardo Gottardi, Steven R. Little
Journal: Advanced Healthcare Materials (2017)

Ocular diseases (ex: dry eye disease, age-related macular degeneration, uveitis) significantly affect the quality of life of millions of individuals each year. In these diseases, a local inflammatory response results in ocular tissue damage. In order to overcome this inflammatory response, new therapeutic controlled release systems are developed to help restore homeostasis in the ocular microenvironment. Steven R. Little and co-workers outline multiple types of therapeutic strategies that aim to either address the symptoms or abate the underlying cause of these diseases in article number 1700733.
Hypoxia Potentiates Notch-Induced Expansion of Human Hematopoietic Stem/Progenitor Cells
Authors: Jianfei Fu, Heather D. Huntsman, Ayla Cash, Patali S. Cheruku, Richard H. Smith, Aibin Liang, Irwin D. Bernstein, Andre Larochelle
Journal: Blood (2016)
Smoking paradox in the development of psoriatic arthritis among patients with psoriasis
Authors: Young Ho Lee, Gwan Gyu Song
Journal: Annals of the Rheumatic Diseases (2017)

We have read with great interest the article by Nguyen and colleagues1 on the smoking paradox in the development of psoriatic arthritis (PsA) among patients with psoriasis. The authors present a large population-based study, in which they demonstrate that smoking is positively associated with PsA risk in the general population but negatively associated with PsA risk among patients with psoriasis, thereby suggesting that index event bias could result in the smoking paradox. The reasons for this smoking paradox are difficult to elucidate, but we agree with the authors’ emphasis on the …
Long esophageal inlet patch as a rare cause of laryngopharyngeal symptoms
Authors: Władysław Januszewicz, Anna Pietrzak, Małgorzata Lenarcik, Andrzej Mróz, Jarosław Reguła
Journal: Endoscopy (2017)

A 31-year-old woman presented to our department with nonspecific laryngopharyngeal symptoms, such as globus sensation, regurgitation, and heartburn, which she had experienced for a few years. Her medical history was irrelevant. An esophagogastroduodenoscopy revealed an irregular Z-line in the distal esophagus without evidence of Barrett’s esophagus ([Fig. 1 a]), and an area of ectopic gastric mucosa in the mid-proximal esophagus, 8 cm in length and at 35 to 27 cm from the incisors, involving more than half of the esophageal lumen ([Fig. 1 b], [Video 1]). Inspection with white-light endoscopy, narrow-band imaging (NBI), and acetic acid staining showed a columnar mucosal pattern with few discrete mucosal irregularities ([Fig. 1 c, d]). Numerous biopsies revealed a fundic-type gastric epithelium with areas of moderate inflammation with no evidence of intestinal metaplasia or dysplasia ([Fig. 2]).
Abstract 19644: Analysis of Recurrent (Including First and Repeat) Primary Endpoint Events (Composite of Heart Failure Hospitalizations and Cardiovascular Death) in PARADIGM-HF
Authors: Ulrik M Mogensen, Jianjian Gong, Pardeep Jhund, Milton Packer, Akshay Desai, Lars Køber, Jean Rouleau, Scott Solomon, Karl Swedberg, Michael Zile, Martin Lefkowitz, Victor Shi, John J McMurray, Guenther Mueller-Velten
Journal: Circulation (2016)

Introduction: In PARADIGM-HF, compared with enalapril (N=4,212), sacubitril/valsartan (N=4,187) reduced the incidence of the primary composite endpoint of cardiovascular (CV) death or heart failure...
Resección endoscopica de lesiones colónicas con infiltracion tumoral submucosa (pT1). Manejo y evolución
Authors: A Jiménez Jurado, A Mora Soler, A Álvarez Delgado, AB Prieto Bermejo, VK Calabuig Mazzola, M García Prada, A González González-Cotorruelo, HM Marcos Prieto, S Del Carmen Martínez, A Rodríguez Pérez
Journal: Endoscopy (2017)

Existen criterios actuales de resección endoscópica curativa en los adenocarcinomas colónicos con infiltración submucosa (pT1). Aunque el manejo y seguimiento es variable.
Blood pressure at early pregnancy and gestational hypertensive disorders: a prospective cohort study in China
Authors: Fanfan Chan, Niannian Chen, Jianrong He, Jinhua Lu, Fanghua Liu, Weidong Li, Wanqing Xiao, Songying Shen, Mingyang Yuan, Kar Keung Cheng, Huimin Xia, Ben Willem Mol, Xiu Qiu
Journal: The Lancet (2017)
Abstract 12474: Nicotinamide Restores Tissue Nad+ and Improves Outcomes in a Murine Model of Cardiac Arrest
Authors: Xiangdong Zhu, Jing Li, Huashan Wang, Chunpei Lee, Terry Vanden Hoek
Journal: Circulation (2016)

Introduction: Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD+ and ATP. Hypothesis: Since NAD+ is required for most metabolic processes that generate ATP, we h...
Abstract 17265: Remnant Cholesterol as a Direct Mediator of Arterial and Cellular Inflammation in Humans
Authors: Sophie J Bernelot Moens, Simone L Verweij, Jan G Schnitzler, Lotte C Stiekema, Siroon Bekkering, Merijn Bos, Anne Langsted, Borge G Nordestgaard, Erik S Stroes, Jeffrey Kroon
Journal: Circulation (2016)

Introduction:  Mendelian randomization studies validated a causal role for remnant cholesterol in cardiovascular disease. Remnant particles can enter the arterial wall, potentially propagating arterial inflammation. Also, they are proposed to accumulate in circulating immune cells and their progenitors, pushing them towards a pro-inflammatory phenotype. We evaluated the impact of elevated levels of remnant cholesterol on inflammatory activity of the arterial wall, phenotype of circulating monocytes, and bone marrow activity in familial dysbetalipoprotenemia subjects with remnant hyperlipidemia (RH).   Methods and Results:  We included 15 RH patients (age 61±8, 64% male, FPLC measured remnant cholesterol: 3.5IQR[2-6]mmol/L) and 13 controls (age 58±6, 64% male, remnant cholesterol 0.4[0.2-0.5]mmol/L). Arterial inflammation, measured with  18 F-FDG PET/CT, revealed a significant increase in RH patients (Aortic target-to-background ratio: 2.79±0.42(SD) vs 2.36±0.24 in controls, p=0.003). Monocytes from RH patients showed an increased number of lipid droplets per monocyte: 8±3(SD) vs 5±2 in controls, p=0.02), with concomitant higher expression of surface integrins (CD11b, CD11c, CD18), measured using flow cytometry. Also RH patients exhibited monocytosis and leukocytosis, with a concomitant 1.2-fold increase of  18 F-FDG uptake in the bone marrow, representing progenitor cell activity.  18 F-FDG uptake in the bone marrow correlated to circulating leukocyte levels (r=0.564). Finally, validating the relationship between plasma remnant cholesterol levels and hematopoietic activity, we found a strong correlation between remnant cholesterol levels and leukocyte counts in the Copenhagen General Population Study (n=103.953, p for trend=5*10 -276 ).   Conclusion:  Patients with RH have increased arterial wall inflammation and are characterized by an inflammatory phenotype of circulating monocytes. Moreover, our observational study as well as validation in a large cohort support a link between remnant cholesterol and bone marrow activity. These findings indicate an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to its relationship with increased CVD risk.