tbuckley/cabot-search huggingface dataset:
Early stage interval breast cancers in African-American women demonstrate ER negative status and more aggressive tumor biology
Authors: Keith A. Dookeran, Elona Sciupokiene, Agne Mackeviciute, Karen Ferrer, Marin Sekosan, Xuezhi Gao, Rocio De La Torre, Lorena Diaz de Leon, Barbara Lukaszczyk, Gehad Elfarra, Yu Wang, Wendy A. Rogowski, Neena Muthyala, Calin Caluser, Howard A. Zaren
Journal: Cancer Research (2004)

5259  It has been suggested that biologic factors may contribute to the limited efficacy of mammography and poorer breast cancer outcomes in African American (AA) women. To further investigate, we retrospectively evaluated tumor biology of interval cancers diagnosed in 254 consecutive AA women with breast cancer at the John Stroger Hospital of Cook County, Minority-Based Community Clinical Oncology Program, which serves the medically-indigent in Chicago. A total of 51 AA women were diagnosed with interval cancers; 30 had AJCC stage 0-1 and 21 had stage 2-4 cancers. For women with stage 0-1 cancers, interval cancers were significantly more likely to be hormone receptor (ER) negative (33% vs. 13% for non-interval cancers; Chi-square p
Abstract 17431: Plasma levels of n-3 Polyunsaturated Fatty Acids and Risk of Hospitalization in Patients with Non-Ischemic Cardiomyopathy
Authors: Savina Nodari, Marco Triggiani, Umberto Campia, Lihui Zhao, Alessandra Manerba, Giuseppe Milesi, Laura Lupi, Cristian Maiandi, Elena Rocco, Livio Dei Cas
Journal: Circulation (2012)

Purpose: n-3 polyunsaturated fatty acids (PUFAs) may lower cardiovascular (CV) risk by exerting antithrombotic, antiarrhythmic and anti-inflammatory effects. However, whether higher baseline (b) le...
Abstract 1329: Combination treatment with CB-839 and romidepsin induces apoptosis and suppresses cell viability in preclinical models of chondrosarcoma
Authors: Tahir N. Sheikh, Parag P. Patwardhan, Gary K. Schwartz
Journal: Cancer Research (2018)

Abstract Chondrosarcomas are the second most frequently occurring type of bone malignancy, and account for approximately 25% of all bone sarcomas. They are often highly aggressive neoplasms that rapidly progress and eventually recur and give distant metastases. They are largely considered to be resistant to conventional chemotherapy and radiotherapy. Several studies have reported that mTORC1 stimulates glutamine metabolism and increased mitogenic signaling through activation of the mTORC pathway, coupled with deregulation of the Cyclin D/retinoblastoma (Rb) pathway is a common feature of certain malignancies. In the present study, we hypothesized that concurrent inhibition of glutamine metabolism and histone acetylation could result in decreased viability of chondrosarcoma cells. To test this, we used a panel of chondrosarcoma cell lines including IDH wild type (CH2879), IDH1 mutant (JJ012) and IDH2 mutant (SW1353) cell line. Results from our in vitro proliferation assay showed that combination of sub-IC50 concentrations of the CB-839 (Glutaminase inhibitor) and Romidepsin (HDAC inhibitor) resulted in decreased cell viability of all the three chondrosarcoma cell lines when compared to either of the two drugs alone. Western blot analysis showed induction of cleaved Poly-ADP Ribose Polymerase (PARP) as well as cleaved caspase 3, known markers of apoptosis and down regulation of mTORC1 targets such as phospho-S6 and Phospho-p44/42 MAPK such as ERK1/2. Combination treatment also resulted in increased induction of histone acetylation (AcH3). Cell cycle analysis showed induction of sub-G1 population phase in combination treatment. Previous reports have shown that CpG methylation is a critical event in transcriptional repression of hyper methylated genes in cancer. To this end, we show that combination treatment with CB-839 and Romidepsin results in down regulation of (H3K9) methylation. Taken together, our data strongly suggests that combination treatment with CB-839 (Glutaminase inhibitor) and Romidepsin (HDAC inhibitor) is a novel treatment approach and merits evaluation in the treatment of chondrosarcoma. Citation Format: Tahir N. Sheikh, Parag P. Patwardhan, Gary K. Schwartz. Combination treatment with CB-839 and romidepsin induces apoptosis and suppresses cell viability in preclinical models of chondrosarcoma [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 1329.
Abstract 13624: A Novel Chymase Inhibitor BAY 1142524 Reduces Fibrosis and Improves Cardiac Function After Myocardial Infarction in Hamster
Authors: Hanna Tinel, Dmitry Zubov, Katja Zimmermann, Adrian Tersteegen, Kirsten Boerngen, Hannah Joerissen, Jens Ackerstaff, Chantal Fuerstner
Journal: Circulation (2017)

Introduction: Adverse cardiac remodeling remains a major problem in many patients after myocardial infarction (MI), triggering left ventricular dysfunction and development of heart failure. Chymase...
Abstract 1279: Passenger mutation landscape in cancer genomes
Authors: Sushant Kumar, Jonathan Warrel, Patrick Mcgillivray, William Meyerson, Shantao Li, Leonidas Salichos, Arif Harmanci, Alexander Fundichely, Calvin Chan, Carl Herrmann, Morten Nielsen, Lucas Lochovsky, Yan Zhang, Xiaotong Li, Ekta Khurana, Gad Getz, Mark Gerstein
Journal: Cancer Research (2018)

Abstract Cancer progression is an evolutionary process during which thousands of somatic variants are accumulated within an individual. In the classic view of cancer progression, a handful of driver variants are thought to give a positive selection advantage to the cancer cell. The remaining variants, termed passengers, represent the overwhelming majority of the variants in cancer genomes, and their functional consequences are poorly understood. Furthermore, the bulk of these passengers fall within noncoding regions of the genome, making these the main product of whole-genome sequencing of tumors. In this work, we explore the functional landscape of passenger variants in various cancer cohorts by leveraging extensive pan-cancer variant calls from ~2500 uniformly processed whole cancer genomes. More specifically, we integrate their annotations and predicted functional impact scores to quantify the overall burdening of various elements in cancer genomes. We show that disruption of genetic regulatory elements in the noncoding genome correlates with altered gene expression. Furthermore, we also show how overall functional burdening of various genomic elements correlate with patient survival time, and tumor clonality. Finally, we observe statistical signals consistent with the notion that aggregated subsets of passenger variants - particularly those we predict to be functionally impactful- might confer weak selective effects. Citation Format: Sushant Kumar, Jonathan Warrel, Patrick Mcgillivray, William Meyerson, Shantao Li, Leonidas Salichos, Arif Harmanci, Alexander Fundichely, Calvin Chan, Carl Herrmann, Morten Nielsen, Lucas Lochovsky, Yan Zhang, Xiaotong Li, Ekta Khurana, Gad Getz, Mark Gerstein. Passenger mutation landscape in cancer genomes [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 1279.
Mutation-Linked Defective Interdomain Interactions Within Ryanodine Receptor Cause Aberrant Ca2+ Release Leading to Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: TakeshiSuetomi, MasafumiYano, HitoshiUchinoumi, MasakazuFukuda, AkihiroHino, MakotoOno, XiaojuanXu, HirokiTateishi, ShinichiOkuda, MasahiroDoi, ShigekiKobayashi, YasuhiroIkeda, TakeshiYamamoto, NoriakiIkemoto, MasunoriMatsuzaki
Journal: Circulation (2011)

Background—The molecular mechanism by which catecholaminergic polymorphic ventricular tachycardia is induced by single amino acid mutations within the cardiac ryanodine receptor (RyR2) remains elusive. In the present study, we investigated mutation-induced conformational defects of RyR2 using a knockin mouse model expressing the human catecholaminergic polymorphic ventricular tachycardia–associated RyR2 mutant (S2246L; serine to leucine mutation at the residue 2246). Methods and Results—All knockin mice we examined produced ventricular tachycardia after exercise on a treadmill. cAMP-dependent increase in the frequency of Ca2+ sparks was more pronounced in saponin-permeabilized knockin cardiomyocytes than in wild-type cardiomyocytes. Site-directed fluorescent labeling and quartz microbalance assays of the specific binding of DP2246 (a peptide corresponding to the 2232 to 2266 region: the 2246 domain) showed that DP2246 binds with the K201-binding sequence of RyR2 (1741 to 2270). Introduction of S2246L muta...
Redifferentiation of Smooth Muscle Cells After Coronary Angioplasty Determined via Myosin Heavy Chain Expression
Authors: MasanoriAikawa, YasunariSakomura, MakikoUeda, KenjiroKimura, IchiroManabe, SugaoIshiwata, NobuyukiKomiyama, HiroshiYamaguchi, YoshioYazaki, RyozoNagai
Journal: Circulation (1997)

Background The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC. Methods and Results To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against α-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for α-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas α-actin was constitutively expressed in all cases studied. Neointimal cell...
Cell Transplantation as Future Therapy for Cardiovascular Disease
Authors: LeslieReinlib, LorenField
Journal: Circulation (2000)

Abstract—Despite the development of improved therapies and the significant advances in the understanding of the basis of disease pathogenesis, millions of Americans continue to live with life-threatening cardiovascular diseases. Recent breakthroughs suggest exciting directions that are likely to produce more effective therapies for the treatment of cardiovascular disease. One such area, cell transplantation (grafting of healthy cells into the diseased heart), holds enormous potential as an approach to cardiovascular pathophysiology. Once thought to be a scientific long shot, cell transplantation is becoming recognized as a viable strategy to strengthen weak hearts and limit infarct growth. The technology could also be used for the long-term delivery of beneficial recombinant proteins to the heart, which is a strategy to complement molecular biology advances and provide an alternative strategy for gene therapy. On August 24, 1998, the National Heart, Lung, and Blood Institute convened a workshop to discuss...
Abstract 4462: RUNX1 global binding and gene regulation in mammary epithelial cells revealed novel Runx1 mediated cellular activities
Authors: Deli Hong, Andrew J. Fritz, Coralee E. Tye, Natalie A. Page, Joseph R. Boyd, Jane B. Lian, Janet L. Stein, Gary S. Stein
Journal: Cancer Research (2018)

Abstract The transcription factor RUNX1 is one of the most frequently mutated genes in breast tumors. However, the role of RUNX1 in the mammary gland is understudied. Previously, our group established that RUNX1 has tumor suppressor activities in both normal mammary epithelial and breast cancer cells, including inhibition of epithelial to mesenchymal transition (EMT), migration, and invasion. To better understand the cellular consequences mediated by RUNX1 loss-of-function in mammary epithelial cells, we performed global gene expression profiling (RNA-seq) in Runx1-depleted MCF10A cells. Upon loss of RUNX1, the expression of 1806 genes was significantly altered (with 2-fold change cutoff). Pathway analysis on these differentially expressed genes revealed that RUNX1 is involved in many cellular activities, including lipid metabolism, cell growth and cell cycle control, which were not previously reported. Consistent with expression profiling results, flow cytometry analysis showed the mitotic population in RUNX1 depleted cells was significantly decreased, indicating RUNX1 is important for proper cell division. To investigate the mechanisms by which RUNX1 controls expression of those differentially expressed genes, RUNX1 genome-wide occupancy analysis (ChIP-seq) was performed in MCF10A cells. We found that although RUNX1 binding is enriched at transcription start sites (TSS), RUNX1 also binds to loci distal to TSSs and multiple other regulatory elements. Therefore, RUNX1 has the capability to utilize multiple mechanisms to control target gene expression. Our results highlight crucial roles for RUNX1 in controlling normal growth of mammary epithelial cells, consistent with its tumor suppressor activities. Loss of RUNX1 leads to improper gene regulation and cell cycle defects, which may contribute to tumor progression in breast cancer. These RUNX1-mediated mechanisms point to novel intervention strategies for early stage breast cancer. Citation Format: Deli Hong, Andrew J. Fritz, Coralee E. Tye, Natalie A. Page, Joseph R. Boyd, Jane B. Lian, Janet L. Stein, Gary S. Stein. RUNX1 global binding and gene regulation in mammary epithelial cells revealed novel Runx1 mediated cellular activities [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 4462.
A quality analysis of internet information for hernia and hernia repair. Using three validated tools: DISCERN instrument, JAMA benchmarks and flesch reading ease score
Authors: T. Patterson, P. Currie, E. Phoenix, J. Beck, C. Beck, C. Meek, I. Ghaffari, J. Moradzadeh, A. Campbell, R. Spence
Journal: International Journal of Surgery (2018)
Dispatcher-Assisted Cardiopulmonary Resuscitation
Authors: LindsayWhite, JosephRogers, MeganBloomingdale, CarolFahrenbruch, LindaCulley, CleoSubido, MickeyEisenberg, ThomasRea
Journal: Circulation (2010)

Background— Dispatcher-assisted cardiopulmonary resuscitation (CPR) instructions can increase bystander CPR and thereby increase the rate of survival from cardiac arrest. The risk of bystander CPR for patients not in arrest is uncertain and has implications for how assertive dispatch is in instructing CPR. We determined the frequency of dispatcher-assisted CPR for patients not in arrest and the frequency and severity of injury related to chest compressions. Methods and Results— The investigation was a prospective cohort study of adult patients not in cardiac arrest for whom dispatchers provided CPR instructions in King County, Washington, between June 1, 2004, and January 31, 2007. The study focused on those who received chest compressions. Information was collected through review of the audio and written dispatch report, written emergency medical services report, hospital record, and telephone survey. Of the 1700 patients for whom dispatcher CPR instructions were initiated, 55% (938 of 1700) were in arre...
Cardioprotection by CaMKII-δB Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70
Authors: WeiPeng, YanZhang, MingZheng, HepingCheng, WeizhongZhu, Chun-MeiCao, Rui-PingXiao
Journal: Circulation Research (2010)

Rationale: Ca2+/calmodulin-dependent protein kinase (CaMK)II is a multifunctional kinase involved in vital cellular processes such as Ca2+ handling and cell fate regulation. In mammalian heart, 2 primary CaMKII isoforms, δB and δC, localize in nuclear and cytosolic compartments, respectively. Although previous studies have established an essential role of CaMKII-δC in cardiomyocyte apoptosis, the functional role of the more abundant isoform, CaMKII-δB, remains elusive. Objective: Here, we determined the potential role of CaMKII-δB in regulating cardiomyocyte viability and explored the underlying mechanism. Methods and Results: In cultured neonatal rat cardiomyocytes, the expression of CaMKII-δB and CaMKII-δC was inversely regulated in response to H2O2-induced oxidative stress with a profound reduction of the former and an increase of the later. Similarly, in vivo ischemia/reperfusion (IR) led to an opposite regulation of these CaMKII isoforms in a rat myocardial IR model. Notably, overexpression of CaMKII...
Abstract 11778: EPC Mobilization After Erythropoietin Treatment in Acute St-elevation Myocardial Infarction: The Reveal EPC Substudy
Authors: Thomas J Povsic, Sunil V Rao, Samer S Najjar, Laura G Melton, Kristi Prather, Jiying Zhou, Stacie D Adams, Katherine L Zavodni, Francine Kelly, Vic Hasselblad, John F Heitner, Subha V Raman, Gregory W Barsness, Manesh R Patel, Raymond J Kim, Edward G Lakatta, Robert A Harrington
Journal: Circulation (2012)

Aims: Erythropoietin (EPO) may mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The multicenter REVEAL trial demonstrated no effect of EPO on infarct si...
Brazil’s child and maternal mortality have increased against background of public spending cuts
Authors: Cláudia Collucci
Journal: BMJ (2018)

Infant mortality in Brazil rose for the first time in more than a quarter of a century in 2016, the same year that an increase in maternal mortality was observed, new data show.1

Figures from the Ministry of Health indicate that the number of infant deaths reached 14 in every 1000 live births in 2016, a 5% increase on the 2015 figure of 13.3. Infant mortality had been falling since standardised statistics began in 1990, when the rate was 47.1 in 1000 live births.

In terms of maternal mortality Brazil committed to reduce deaths by …
Priming With Angiopoietin-1 Augments the Vasculogenic Potential of the Peripheral Blood Stem Cells Mobilized With Granulocyte Colony-Stimulating Factor Through a Novel Tie2/Ets-1 Pathway
Authors: Min-SeokKim, Choon-SooLee, JinHur, Hyun-JaiCho, Soo-InJun, Tae-YounKim, Sae-WonLee, Jung-WonSuh, Kyung-WooPark, Hae-YoungLee, Hyun-JaeKang, Dong-SooLee, Gou-YoungKoh, HironoriNakagami, RyuichiMorishita, Young-BaePark, Hyo-SooKim
Journal: Circulation (2009)

Background— The low engraftment rate of stem/progenitor cells infused via the intracoronary route to the ischemic myocardium is one of the most important factors limiting the efficacy of cell therapy. We investigated the concept of priming peripheral blood stem cells enriched by granulocyte colony-stimulating factor mobilization and apheresis (mobPBSCs) with angiopoietin-1 (Ang1), to enhance the engraftment into the ischemic tissue and neovasculogenic potential. Methods and Results— The expression of Tie2, the Ang1 receptor, was significantly higher in mobPBSCs than naive peripheral blood mononuclear cells (19.2±3.0% versus 1.2±0.8% versus 1.2±0.2%; P<0.001 for mobPBSCs from acute myocardial infarction (AMI) patients with granulocyte colony-stimulating factor treatment for 3 days versus peripheral blood mononuclear cells from AMI patients versus peripheral blood mononuclear cells from stable angina patients). After 4 hours of cartilage oligomeric matrix protein (COMP)-Ang1 stimulation, mobPBSCs committed...
Abstract 5524: Tumor suppressor Numb represses monocarboxylate transporters to reduce the glycolysis in oral carcinoma
Authors: Chung-Hsien Chou, Chun-Yu Fan Chaing, Shu-Chun Lin, Kuo-Wei Chang, Hsi-Feng Tu
Journal: Cancer Research (2018)

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Our previous studies have shown that Numb pluripotent gene drives suppressor activity against OSCC, and it is co-targeted by multiple oncogenic miRNAs. In this study, we further identified that Numb mRNA expression was down-regulated in a large fraction of OSCC tumors. We established the Numb-knockout (KO) OSCC cell subclones using CRISPR-Cas9 system. We also generated lentiviruses for exogenous expression of Numb 1 and Numb 4 isoforms. The anchorage independent growth potential was found increased in Numb-KO cell subclones. However, such eligibility was repressed after the rescue of the Numb expression by lentiviral infection. In addition, the level of lactate production and the ratio of ECAR/OCR in the Numb-KO cell subclones were higher than parental cells. The knockout of Numb was able to up-regulate the expression of monocarboxylate transporter (MCT) family members MCT1 and MCT4, but not other metabolism genes, to increase the lactate production. Knockdown of both MCT1 and MCT4 significantly decreased the anchorage independent growth and the lactate production of OSCC cells. This study provides new evidences denoting that Numb represses MCTs to attenuate the transformative capability and the glycolysis in oral carcinoma. Citation Format: Chung-Hsien Chou, Chun-Yu Fan Chaing, Shu-Chun Lin, Kuo-Wei Chang, Hsi-Feng Tu. Tumor suppressor Numb represses monocarboxylate transporters to reduce the glycolysis in oral carcinoma [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 5524.
Abstract 18659: Electrical Stimulation of the Intact Right Cervical Vago-Sympathetic Trunk Decreases Myocardial Norepinehrine Spillover in the Setting of Sympathetic Activation
Authors: Carlos L del Rio, Gail E Geist, Bradley L Youngblood, Erin Ferris, Yukie Ueyama, Mary Cismowski, George E Billman, Peter J Schwartz
Journal: Circulation (2016)

Introduction: Cervical vagus nerve electrical stimulation (VNS) has been shown to improve functional indices in the setting of heart failure with depressed parasympathetic control. However, the cer...
Auscultatory and Phonocardiographic Assessment of Fallot's Tetralogy
Authors: Louisvogelpoel, Velvaschrire
Journal: Circulation (1960)

A clinical and phonocardiographic study has been made on 62 cases of Fallot's tetralogy in order to determine the value of auscultation and phonocardiography in assessing the severity of the stenosis. The severity of the tetralogy, as determined by clinical methods, was correlated with the length and loudness of the murmur and other auscultatory signs. Increasingly severe stenosis was shown to be associated with a shorter, earlier, and softer systolic murmur. In extreme tetralogy, the murmur was invariably soft and very short, being confined to early systole and ending in midsystole. An aortic ejection sound was usually audible and the second sound invariably loud and single. In severe tetralogy, the murmur was usually loud and short, with its crescendo before midsystole and termination before the aortic second sound. A pulmonary component was never audible. In moderate cases, the murmur was loud and longer, with its crescendo at midsystole and termination before or at the aortic second sound, which was n...
A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus
Authors: Wiebke Fenske, Julie Refardt, Irina Chifu, Ingeborg Schnyder, Bettina Winzeler, Juliana Drummond, Antônio Ribeiro-Oliveira, Tilman Drescher, Stefan Bilz, Deborah R. Vogt, Uwe Malzahn, Matthias Kroiss, Emanuel Christ, Christoph Henzen, Stefan Fischli, Anke Tönjes, Beat Mueller, Jochen Schopohl, Jörg Flitsch, Georg Brabant, Martin Fassnacht, Mirjam Christ-Crain
Journal: New England Journal of Medicine (2018)

The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.