tbuckley/cabot-search huggingface dataset:
Abstract PL04-04: Oncohistones in cancer: How to turn a cell's symphony into non harmonic rap
Authors: Nada Jabado
Journal: Cancer Research (2018)

Abstract Recent studies have shown that chromatin-associated proteins and transcription factors have more somatic alterations than any other class of oncoproteins in childhood CNS tumors. Different Histone H3 genes (H3F3A, Hist3.1B) and variants (K27, G34, K36) can be affected with remarkable specific association between tumor location and type as well as the particular H3 residue or variant that is mutated. We have shown a high prevalence of H3 mutations in pediatric and young adult High Grade Astrocytoma, in sarcomas such as Giant Cell Tumors of the bone and chondroblastomas, and most recently, in Head and Neck Squamous Cell Carcinomas. These ground-breaking discoveries of oncohistones implicate a direct effect of epigenetic misregulation in oncogenesis. Here, we describe these epigenetic misfits and our knowledge of their effects, along with novel tools needed to study them. We will also discuss how we are harnessing synergies between the approaches of cancer genomics and chemical biology to help make sense of the pathogenesis of oncohistones and describe how oncohistones are promoting global redistribution of important epigenetic marks, seemingly hijacking our epigenome. Citation Format: Nada Jabado. Oncohistones in cancer: How to turn a cell's symphony into non harmonic rap [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr PL04-04.
Dyspnea and Edema in a Woman With Antiphospholipid Syndrome
Authors: Ersilia M. DeFilippis, Allison L. Tsao, Joseph Loscalzo
Journal: JAMA Cardiology (2018)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Abstract 32: BCL11A is necessary for the expression of extracellular matrix genes and metastatic progression of triple-negative breast cancer
Authors: Darcie D. Seachrist, Natasha N. Ingles, Molly M. Hannigan, Donny D. Licatalosi, Ruth A. Keri
Journal: Cancer Research (2018)

Abstract Cancer stem cells (CSC) contribute to the high incidence of metastatic recurrence in triple-negative breast cancer (TNBC) and elucidating the mechanisms controlling CSC properties should provide novel targets for therapeutic development that improves patient outcomes. The transcription factor BCL11A is highly differentially expressed in TNBC versus all other subtypes and controls breast CSC phenotypes such as marker expression and tumor initiation. However, the genes that BCL11A targets to control CSC biology and whether BCL11A promotes metastatic progression are unknown. To address these questions, we assessed the impact of transiently silencing the expression of BCL11A in TNBC cells using siRNA transfections. Reducing BCL11A expression did not impact TNBC cell viability or in vitro migratory capacity. However, silencing BCL11A significantly decreased invasion of TNBC cell lines, in vitro. Furthermore, stable shRNA-mediated silencing of BCL11A in the highly metastatic MDA-MB-231 cell line reduced metastatic outgrowth when xenografted into immunocompromised mice, suggesting that BCL11A is critical for metastatic progression of TNBC. To identify the BCL11A-regulated transcriptome in TNBC, we performed RNA-seq analysis of cells transiently transfected with non-targeting or BCL11A-targeted siRNAs in the MDA-MB-231 cell line. Consistent with the impact of BCL11A on invasion, numerous genes involved in adhesion and extracellular matrix were reduced with BCL11A silencing. The gene encoding the matrix metalloproteinase, MMP1, was the most significantly differentially expressed gene, with a 10-fold decrease in RNA expression following BCL11A suppression. We confirmed this down-regulation by both qRT-PCR and western blots of independent samples, as well as in the HCC1143 TNBC cell line. Current studies are assessing the functional impact of MMP1 regulation by BCL11A on invasion and metastatic progression of TNBC. Citation Format: Darcie D. Seachrist, Natasha N. Ingles, Molly M. Hannigan, Donny D. Licatalosi, Ruth A. Keri. BCL11A is necessary for the expression of extracellular matrix genes and metastatic progression of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 32.
Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells
Authors: Subhrajit Bhattacharya, Alpa Khatri, Sharon A. Swanger, John O. DiRaddo, Feng Yi, Kasper B. Hansen, Hongjie Yuan, Stephen F. Traynelis
Journal: Neuron (2018)
Lung Function Reference Values in Chinese Children and Adolescents in Hong Kong
Authors: MARY S. M. IP, EVA M. KARLBERG, KWOK-NING CHAN, JOHAN P. E. KARLBERG, KEITH D. K. LUK, JOHN C. Y. LEONG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

As part of a comprehensive evaluation of lung function in Hong Kong Chinese children and adolescents, over a thousand healthy subjects aged 7–19 yr from seven schools were recruited for lung function testing that included spirometry and, in many cases, lung subdivision measurements. Lung function tests were performed using SensorMedics Automated Body Plethysmograph according to published standards. Of these, 551 subjects (219 males), aged 8–19 yr, had satisfactory lung subdivision indices recorded. Analysis for the values of lung subdivisions including total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) demonstrated that standing height and sitting height were the best predictors of lung volumes. After allowing for standing height or sitting height in the regression models for lung volumes, age at examination was the second best parameter, although its inclusion into the equations contributed to less than 1% of explained variance for boys and 3% for girls. These are the first reported data in international literature on reference values for lung subdivisions in Chinese children and adolescents.
Adiposity and risk of ischaemic and haemorrhagic stroke in Chinese men and women: a prospective study of 0.5 million adults
Authors: Z Chen, A Iona, S Parish, Y Chen, Y Guo, F Bragg, L Yang, M Holmes, S Lewington, B Lacey, R Walters, R Collins, R Clarke, R Peto
Journal: The Lancet Global Health (2018)
Abstract 97: UBE3A regulates SIRT6 levels to promote tumorigenesis in an ANXA2 dependent manner
Authors: Saishruti Kohli, Sanjeev Das
Journal: Cancer Research (2018)

Abstract Background: UBE3A is the founding member of the HECT family of E3 ubiquitin ligases, implicated in cervical, prostate and breast cancer. A recent study has reported that UBE3A promotes proliferation and invasiveness of cancer cells by inducing Annexin A2 (ANXA2) levels. We have delineated a cascade in which UBE3A brings about the proteasomal degradation of SIRT6. Furthermore, we have also established that SIRT6 transcriptionally regulates ANXA2 expression. Here, we have confirmed that UBE3A-mediated SIRT6 downregulation and consequent derepression of ANXA2 promotes tumor metastasis. Methods: HepG2, a Hepatocellular carcinoma cell line, was used to study the effects of the UBE3A-SIRT6-AXA2 axis. HepG2 UBE3A knockdown, SIRT6 knockdown, UBE3A/SIRT6 double knockdown and SIRT6/ANXA2 double knockdown cells were used to examine in-vitro cell proliferation, invasion, plasmin generation and MMP activation. These cell lines were also used for obtaining subcutaneous and orthotopic xenografts in immunodeficient mice and multiple parameters were analyzed to determine tumor growth and metastases. Results: We observed that upon UBE3A abrogation, cells exhibited reduced tumor-forming potential and resulted in smaller tumors with low metastasis. On the other hand, increased tumorigenesis, and much larger tumors with increased metastasis were observed upon SIRT6 knockdown, which was significantly reversed upon simultaneous knockdown of UBE3A. Furthermore, smaller tumors were observed in case of SIRT6/ANXA2 double knockdown cells as compared to UBE3A/SIRT6 double knockdown cells. These results suggest that UBE3A-mediated ANXA2 upregulation, via SIRT6 degradation, is critical for its oncogenic functions Conclusion: UBE3A mediated SIRT6 degradation leads to ANXA2 upregulation and hence enhances tumorigenesis. It would be beneficial to identify drugs targeting UBE3A as a therapeutic approach in hepatocellular carcinoma. Alternatively, mechanisms which inhibit ANXA2 activity must be deciphered to identify druggable targets. Citation Format: Saishruti Kohli, Sanjeev Das. UBE3A regulates SIRT6 levels to promote tumorigenesis in an ANXA2 dependent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 97.
Peak ACL force during jump landing in downhill skiing is less sensitive to landing height than landing position
Authors: Dieter Heinrich, Antonie J van den Bogert, Werner Nachbauer
Journal: British Journal of Sports Medicine (2018)

Competitive skiers face a high risk of sustaining an ACL injury during jump landing in downhill skiing. There is a lack of knowledge on how landing height affects this risk.To evaluate the effect of varied landing height on peak ACL force during jump landing and to compare the effect of the landing height with the effect of the landing position varied by the trunk lean of the skier.A 25-degree-of-freedom sagittal plane musculoskeletal model of an alpine skier, accompanied by a dynamic optimisation framework, was used to simulate jump landing manoeuvres in downhill skiing. First, a reference simulation was computed tracking experimental data of competitive downhill skier performing a jump landing manoeuvre. Second, sensitivity studies were performed computing 441 landing manoeuvres with perturbed landing height and trunk lean of the skier, and the corresponding effects on peak ACL force were determined.The sensitivity studies revealed that peak ACL force increased with jump height and backward lean of the skier as expected. However, peak ACL was about eight times more sensitive to the trunk lean of the skier compared with landing height. The decreased sensitivity of the landing height was based on the lower effects on the knee muscle forces and the shear component of the knee joint reaction force.Preventive measures are suggested to focus primarily on avoiding trunk backward lean of the skier, and consequently on proper jump preparation and technique, and secondarily on strategies to reduce landing height during jumps.
A marked shift in innate and adaptive immune response in chinese immigrants living in a western environment
Authors: Aarti Saiganesh, Belinda J. Hales, Yuchun Li, Patrick G. Holt, Peter N. Le Souëf, Guicheng Zhang
Journal: Allergy (2018)

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Abstract LB-023: Describing prostate cancer heterogeneity through single cell analysis with mass cytometry
Authors: Laura De Vargas Roditi, Andrea Jacobs, Christian Fankhauser, Cedric Poyet, Peter Wild, Bernd Bodenmiller
Journal: Cancer Research (2018)

Abstract Background Single-cell analysis has emerged as a crucial approach to detect variations in genetic and proteomic expression. Prostate cancer is characterized by multiple genomic alterations leading to the complex nature of the disease. The heterogeneity at the proteomic level is not yet well characterized, yet intra-tumor heterogeneity can impair correct diagnosis and treatment, by driving therapy resistance. Meanwhile inter-tumor heterogeneity can strongly impact personalization of treatments highlighting the importance of characterizing both intra- and inter-tumor heterogeneity. Using single-cell mass cytometry data, we identify the proteomic profiles of the different cellular subpopulations found in prostate cancer that are common across a cohort of 50 patients while also describing the variations across patients, thus thoroughly characterizing prostate tumor heterogeneity. Methods &amp; Results Mass cytometry experiments allow quantification of dozens of proteins simultaneously at the single-cell level, for thousands of cells. The high dimensionality of this data represents a challenge for data visualization and clustering, which require computational approaches for interpretation of the results. We developed a new computational method to address this task and analyzed tissue sections from surgically removed prostates from 50 patients using mass cytometry with a comprehensive set of 40 antibodies to jointly identify surface markers, enzymes, transcription factors and functional readouts. Conclusions Here, we present for the first time an analysis of prostate tumor cell heterogeneity by mass cytometry coupled to a newly developed computational method that improves visualization and clustering of such high-dimensional data. This study was conducted by analyzing prostate cancer samples from fifty patients at the single-cell level using mass cytometry to estimate the abundance of forty different proteins simultaneously for each cell. Our results show that immune, stromal and epithelial cells can be comprehensively distinguished across all patients. A closer look at the epithelial compartment reveals multiple subpopulations which we describe in terms of their protein expression patterns to characterize the intra- and inter-tumor heterogeneity in prostate cancer. This work demonstrates how single cell phenotypic profiles of prostate tumor cells, taken from surgically removed prostates, can be used to quantify the varying heterogeneity during tumor progression. Citation Format: Laura De Vargas Roditi, Andrea Jacobs, Christian Fankhauser, Cedric Poyet, Peter Wild, Bernd Bodenmiller. Describing prostate cancer heterogeneity through single cell analysis with mass cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-023.
Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI‐551) and Correlates With Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease
Authors: Katie Streicher, Sriram Sridhar, Mike Kuziora, Christopher A. Morehouse, Brandon W. Higgs, Yinong Sebastian, Christopher J. Groves, Fernanda Pilataxi, Philip Z. Brohawn, Ronald Herbst, Koustubh Ranade
Journal: Arthritis & Rheumatology (2018)

B cells impact the progression of systemic sclerosis (SSc; scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. PC depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated the effects of PC depletion on SSc disease activity.A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase I clinical trials. We assessed microarray data from tissue from public studies of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic dermatitis, as well as blood from a phase IIb clinical trial in SLE.The PC signature was elevated in SSc skin specimens compared to healthy donor skin (P = 2.28 × 10-6 ) and correlated with the baseline modified Rodnan skin thickness score (MRSS) (r = 0.64, P = 0.0004). Patients with a high PC signature at baseline showed greater improvement in the MRSS (mean ± SD change 35 ± 16%; P = 6.30 × 10-4 ) following anti-CD19 treatment with inebilizumab (MEDI-551) than did patients with a low PC signature at baseline (mean ± SD change 8 ± 12%; P = 0.104). The PC signature was overexpressed in tissue from patients with SLE, DM, COPD, interstitial lung disease, and IPF relative to controls (all fold change >2; P < 0.001). The PC signature also differed significantly between SLE patients with mild-to-moderate disease and those with severe disease (SLE Disease Activity Index cutoff at 10) (fold change 1.44; P = 3.90 × 10-3 ) and correlated significantly with the degree of emphysema in COPD (r = 0.53, P = 7.55 × 10-8 ).Our results support the notion that PCs have a role in the pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated pretreatment PC signature was associated with increased benefit from MEDI-551 in SSc.
Association of Maternal Diabetes With Neonatal Outcomes of Very Preterm and Very Low-Birth-Weight Infants
Authors: Martina Persson, Prakesh S. Shah, Franca Rusconi, Brian Reichman, Neena Modi, Satoshi Kusuda, Liisa Lehtonen, Stellan Håkansson, Junmin Yang, Tetsuya Isayama, Marc Beltempo, Shoo Lee, Mikael Norman
Journal: JAMA Pediatrics (2018)

Diabetes in pregnancy is associated with a 2-times to 3-times higher rate of very preterm birth than in women without diabetes. Very preterm infants are at high risk of death and severe morbidity. The association of maternal diabetes with these risks is unclear.To determine the associations between maternal diabetes and in-hospital mortality, as well as neonatal morbidity in very preterm infants with a birth weight of less than 1500 g.This retrospective cohort study was conducted at 7 national networks in high-income countries that are part of the International Neonatal Network for Evaluating Outcomes in Neonates and used prospectively collected data on 76 360 very preterm, singleton infants without malformations born between January 1, 2007, and December 31, 2015, at 24 to 31 weeks' gestation with birth weights of less than 1500 g, 3280 (4.3%) of whom were born to diabetic mothers.Any type of diabetes during pregnancy.The primary outcome was in-hospital mortality. The secondary outcomes were severe neonatal morbidities, including intraventricular hemorrhages of grade 3 to 4, cystic periventricular leukomalacia, retinopathy of prematurity needing treatment and bronchopulmonary dysplasia, and other morbidities, including respiratory distress, treated patent ductus arteriosus, and necrotizing enterocolitis. Odds ratios (ORs) with 95% confidence intervals were estimated, adjusted for potential confounders, and stratified by gestational age (GA), sex, and network.The mean (SD) birth weight of offspring born to mothers with diabetes was significantly higher at 1081 (262) g than in offspring born to mothers without diabetes (mean [SD] birth weight, 1027 [270] g). Mothers with diabetes were older and had more hypertensive disorders, antenatal steroid treatments, and deliveries by cesarean delivery than mothers without diabetes. Infants of mothers with diabetes were born at a later GA than infants of mothers without diabetes. In-hospital mortality (6.6% vs 8.3%) and the composite of mortality and severe morbidity (31.6% vs 40.6%) were lower in infants of mothers with diabetes. However, in adjusted analyses, no significant differences in in-hospital mortality (adjusted OR, 1.16 (95% CI, 0.97-1.39) or the composite of mortality and severe morbidity (adjusted OR, 0.99 (95% CI, 0.88-1.10) were observed. With few exceptions, outcomes of infants born to mothers with and without diabetes were similar regardless of infant sex, GA, or country of birth.In high-resource settings, maternal diabetes is not associated with an increased risk of in-hospital mortality or severe morbidity in very preterm infants with a birth weight of fewer than 1500 g.
Increases in atmospheric carbon dioxide: Anticipated negative effects on food quality
Authors: Kristie L. Ebi, Lewis H. Ziska
Journal: PLoS Medicine (2018)

Higher atmospheric concentrations of carbon dioxide (CO 2 ) increase the growth of cereal crops.• At the same time, CO 2 decreases the nutritional value of key staple crops, particularly rice and wheat, by lowering concentrations of protein, micronutrients, and B vitamins.
Abstract 85: Oleic acid promotes head and neck squamous cell carcinoma anoikis resistance and metastasis via ANGPTL4/fibronectin pathway
Authors: Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Kwang-Yu Chang, Wen-Chang Chang, Ben-Kuen Chen
Journal: Cancer Research (2018)

Abstract Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion. In addition, the expression of peroxisome proliferator-activated receptor (PPAR) was essential for the OA-induced ANGPTL4 expression and invasion. The levels of OA-induced epithelial-mesenchymal transition markers, such as vimentin, MMP-9, and fibronectin and its downstream effectors Rac1/Cdc42, were significantly reduced in ANGPTL4-depleted cells. Knocking down fibronectin not only inhibited the expression of MMP-9 but also repressed OA- and recombinant ANGPTL4-induced HNSCC invasion. On the other hand, ANGPTL4 siRNA inhibited OA-induced MMP-9 expression, which was reversed in fibronectin-overexpressing cells. Furthermore, the depletion of ANGPTL4 impeded the OA-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that OA enhances HNSCC metastasis through the ANGPTL4/fibronectin/Rac1/Cdc42 and ANGPTL4/fibronectin/MMP-9 signaling axes. The inhibition of ANGPTL4 could be a potential strategy for the treatment of FFA-mediated HNSCC metastasis. Citation Format: Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Kwang-Yu Chang, Wen-Chang Chang, Ben-Kuen Chen. Oleic acid promotes head and neck squamous cell carcinoma anoikis resistance and metastasis via ANGPTL4/fibronectin pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 85.