tbuckley/cabot-search huggingface dataset:
Abstract 2650: Clinical implication of microsatellite instability in early gastric cancer
Authors: Yoon Young Choi, Dong Gyu Kim, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh
Journal: Cancer Research (2018)

Abstract Purpose: The role of microsatellite instability is well established in advanced gastric cancer. However, its clinical implication has not been well addressed in early gastric cancer. The purpose of this study is to evaluate the clinical characteristics of microsatellite instability in early gastric cancer. Methods: Patients who underwent gastrectomy with curative intent in Severance hospital from January, 2005 to December, 2010 and diagnosed as early gastric cancer (pT1a/b) were enrolled in this study. Remnant gastric cancer and patients who received chemotherapy before operation were excluded. Microsatellite instability status was evaluated by two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250) and instability in two or more markers was defined as miscrosatellite instability high (MSI-H), otherwise classified as microsatellite stable (MSS). Results: Of 1156 tumors that included the final analysis, 85 (7.4%) were MSI-H. MSI-H cancer was related to frequent female gender (54.1% vs. 32.8%, p&amp;lt;0.001), older age (63.4 ± 10.65 vs. 56.7 ± 11.50, p&amp;lt;0.001), lower body (81.2% vs. 59.7%, p=0.002), intestinal histology (63.5% vs. 48.2%, p=0.005), lympho-vascular invasion (25.9% vs. 13.3%, p=0.001), submucosal invasion (63.5% vs. 48.3%, p=0.007), and trend of lymph node metastasis (17.6% vs. 10.8%, p=0.056) compared to MSS type. Lymph node metastasis and lymph-vascular invasion was not differed by MSI status in mucosal gastric cancer (3.2% vs. 2.3%, p=0.755 and 3.2% vs. 2.3%, p=0.755, respectively). In sumbucosal gastric cancer, however, lympho-vascular invasion was frequently observed in MSI-H tumor (38.9% vs. 25.0%, p=0.027) but there was no difference in lymph node metastasis (25.9% vs. 19.9%, p=0.298). When we compared the disease free survival by MSI status, the prognosis of MSI-H tumor was similar compared to that of MSS tumor (log-rank test p=0.797, adjusted Hazard ratio of MSI-H by age, sex, pTstage and number of metastatic LNs: 0.932 [95% confidence interval: 0.423-2.054, p=0.861]). Conclusions: MSI status could not be a useful biomarker in early gastric cancer to predict prognosis of it. However, frequent lympho-vascular invasion of MSI-H early gastric cancer would be a warning that careful patient's selection for endoscopic treatment or limited lymph node dissection for surgery is necessary. Citation Format: Yoon Young Choi, Dong Gyu Kim, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh. Clinical implication of microsatellite instability in early gastric 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 2650.
US National Trends in Violent and Unintentional Injuries, 2000 to 2016
Authors: Ryan A. Lawless, Ernest E. Moore, Mitchel J. Cohen, Hunter B. Moore, Angela Sauaia
Journal: JAMA Surgery (2018)

This study examines temporal patterns of injury fatalities in the United States from 2000 to 2016 by querying the WISQARS database for trends of fatal injuries, stratified by intent (homicides, suicides, or unintentional), major racial/ethnic groups, and injury mechanism.
Effect of Endothelin-1 on Actomyosin ATPase Activity
Authors: GeorgeMcClellan, AndreaWeisberg, SaulWinegrad
Journal: Circulation Research (1996)

Abstract Endothelin is a powerful inotropic peptide that increases isometric force in isolated papillary muscle and the extent of shortening in isolated single cardiac myocytes. Its mechanism of action has been variously attributed to increased Ca2+ activation, increased Ca2+ sensitivity of the contractile proteins, and increased intracellular pH, but the physiological function of the changes in cardiac performance remains obscure. In this study, the effects of endothelin-1 on both force development and the kinetics of contraction have been examined. Isometric force, actomyosin ATPase activity, and unloaded shortening velocity were measured. The effects were dose dependent. From 1 to 50 pmol/L endothelin-1 did not alter force development in isolated trabeculae with intact endothelial cells, but actomyosin ATPase activity was increased. Between 100 pmol/L and 10 nmol/L endothelin-1 raised isometric force, decreased actomyosin ATPase activity, and decreased unloaded shortening velocity. The reduction in ATP...
Abstract 19905: Comparative and Synergistic Effects of an Inhibitor of Integrin Outside-in Signaling With Clopidogrel and Aspirin in Inhibiting Arterial Thrombosis, and Their Different Effects on Hemostasis
Authors: XiangShen, AleksandraStojanovic-Terpo, BoShen, XiaopingDu
Journal: Circulation (2015)

Due to shared mechanisms of thrombosis and hemostasis, all current anti-thrombotic drugs in clinical use, including anti-coagulant and anti-platelet drugs, are associated with increased bleeding risks, which can be life-threatening. Thus, there is a need for developing new anti-thrombotics that minimally cause excessive bleeding. We have recently shown that integrin outside-in signaling, which plays an important role in occlusive thrombosis but is not required for primary platelet thrombus formation, is mediated via the interaction between integrin [[Unsupported Character - Symbol Font ]]3 subunit and heterotrimeric G protein, G[[Unsupported Character - Symbol Font ]]13. We have developed a novel inhibitor of integrin-G[[Unsupported Character - Symbol Font ]]13 interaction, mP6, which inhibits thrombosis without causing excessive bleeding in mouse models. In this study, we have directly compared effects of an improved formulation of mP6, M2mP6, with current anti-platelet drugs clop...
North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies
Authors: Urvi A. Shah, Elaine Y. Chung, Orsi Giricz, Kith Pradhan, Keisuke Kataoka, Shanisha Gordon-Mitchell, Tushar D. Bhagat, Yun Mai, Yongqiang Wei, Elise Ishida, Gaurav S. Choudhary, Ancy Joseph, Ronald Rice, Nadege Gitego, Crystall Parrish, Matthias Bartenstein, Swati Goel, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Adam Binder, Kira Gritsman, Noah Kornblum, Ira Braunschweig, Chirag Bhagat, Jeff Hall, Armin Graber, Lee Ratner, Yanhua Wang, Seishi Ogawa, Amit Verma, B. Hilda Ye, Murali Janakiram
Journal: Blood (2018)
First Human Experience With Pulmonary Vein Isolation Using a Through-the-Balloon Circumferential Ultrasound Ablation System for Recurrent Atrial Fibrillation
Authors: AndreaNatale, EnnioPisano, JeannieShewchik, DiannaBash, RaffaeleFanelli, DomenicoPotenza, PietroSantarelli, RobertSchweikert, RichardWhite, WalidSaliba, LoganKanagaratnam, PatrickTchou, MichaelLesh
Journal: Circulation (2000)

Background—Standard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. Methods and Results—Fifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the...
Role of the Ubiquitin Proteasome System in the Heart
Authors: JuliaPagan, TiffanySeto, MichelePagano, AntonioCittadini
Journal: Circulation Research (2013)

Proper protein turnover is required for cardiac homeostasis and, accordingly, impaired proteasomal function appears to contribute to heart disease. Specific proteasomal degradation mechanisms underlying cardiovascular biology and disease have been identified, and such cellular pathways have been proposed to be targets of clinical relevance. This review summarizes the latest literature regarding the specific E3 ligases involved in heart biology, and the general ways that the proteasome regulates protein quality control in heart disease. The potential for therapeutic intervention in Ubiquitin Proteasome System function in heart disease is discussed.
Abstract 3339: Modulating TAK1 expression through the inhibition of GSK3 impairs YAP/TAZ oncogenic functions in pancreatic cancer
Authors: Raffaela Santoro, Marco Zanotto, Geny Piro, Carmine Carbone, Giampaolo Tortora, Davide Melisi
Journal: Cancer Research (2018)

Abstract Background: Resistance to chemotherapeutic drugs poses one of the greatest challenges in pancreatic cancer (PC) treatment. TGFβ-activated kinase 1 (TAK1) has been demonstrated to drive chemoresistance in PC through the phosphorylation-dependent activation of the NF-κB transcription factor. The transcriptional regulators Yes Associated Protein (YAP) and transcriptional coactivator with a PDZ binding domain (TAZ) are central determinants of malignancy and have been identified as a critical oncogenic effectors of KRAS in PC. We hypothesized that TAK1 could drive PC aggressiveness by sustaining YAP and TAZ oncogenic activities. Methods: TAK1 expression was silenced by shRNA in AsPC1, Panc1, and MDA-Panc28 cell lines. GSK3 was targeted by using the small molecule inhibitor LY2090314. The expression of TAK1, YAP/TAZ and their target genes in PC cell lines was studied by both Western blot and qPCR. Cell migration was assessed by transwell assays, and stemness by both spheroid formation and percentage of cancer stem cells (CSC). SRB assays were used to assess the in vitro chemopotentiation of nab-paclitaxel, gemcitabine, oxaliplatin, and SN-38. In vivo activity of LY2090314 alone or in combination with nab-paclitaxel was evaluated in an orthotopic nude mouse model with luciferase-expressing AsPC1 tumors. Expression of YAP/TAZ target genes in tumor samples was measured by both qPCR and IHC. Results: knockdown of TAK1 resulted in inhibition of K48-linked ubiquitination and proteasomal degradation of YAP and TAZ, which was independent on TAK1 kinase activity. Significant reduction of proliferation, migration and chemoresistance of shTAK1 PC cell lines was also observed. Treatment with LY2090314 induced silencing of TAK1, as well as a remarkable reduction of the expression of both YAP and TAZ and their targets. In combination, the GSK3 inhibitor strongly potentiated the cytotoxic activities of chemotherapeutic agents in all three PC cell lines. In nude mice, i.p. admnistration of LY2090314 plus nab-paclitaxel significantly reduced tumor burden. Conclusions: Our study identified GSK3 and TAK1 as major modulators of YAP and TAZ stability and oncogenic activities, thus indicating that inhibition of TAK1 expression by modulating GSK3 activity could represent a valid approach to revert in vivo the intrinsic chemoresistance of PC. Citation Format: Raffaela Santoro, Marco Zanotto, Geny Piro, Carmine Carbone, Giampaolo Tortora, Davide Melisi. Modulating TAK1 expression through the inhibition of GSK3 impairs YAP/TAZ oncogenic functions in pancreatic 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 3339.
Influence of Deformability of Human Red Cells upon Blood Viscosity
Authors: HOLGERSCHMID-SCHöNBEIN, Roewells, Jerrygoldstone
Journal: Circulation Research (1969)

The viscosity of blood at high rates of shear is unusually low compared to other suspensions of similar concentration. The underlying mechanisms were studied by rotational viscometry, red cell filtration, viscometry of packed cells and direct microscopic observation of red cells under flow in a transparent cone plate viscometer. Deformability of red cells was altered osmotically or abolished by aldehyde fixation. The normal red cells under isosmotic conditions passed easily through filter pores (5 to 14 µ diameter). After osmotic crenation, deformability of cells in pore flow was reduced. Normal cells were deformed into a variety of shapes at high rates of shear, while crenated cells tumbled undeformed. Suspensions of these normal cells showed more pronounced shear thinning (reduction of viscosity with increasing shear rate) than suspensions of crenated cells. Suspensions of rigid cells showed greatly increased viscosity and a shear thickening as a function of shear rate and shear time. The physiological ...
Abstract 14645: Three Dimensional Ejection Fraction is More Strongly Determined by Strain Than by Torsion in a Cohort of Breast Cancer Patients Undergoing Anthracycline-Based Chemotherapy
Authors: Gaurav Gulati, Benjamin French, Kathleen W Zhang, Hari K Narayan, Akinyemi Bajulaiye, Carina Zhang, David Hyman, Bonnie Ky
Journal: Circulation (2015)

Introduction: Anthracycline cardiotoxicity affects approximately 10-20% of treated individuals, representing a significant health burden. Three dimensional (3D) echocardiographic measures of myocardial mechanics have the potential to improve our understanding of the functional changes that occur with anthracyclines, and may play an important role in cardiotoxicity risk prediction. Our objective was to define the relationships between 3D myocardial deformation parameters and left ventricular ejection fraction (LVEF) in a longitudinal, prospective cohort of patients with breast cancer. Methods: We performed 3D echocardiograms at standardized intervals in a longitudinal cohort of women with breast cancer undergoing doxorubicin therapy with or without trastuzumab. We acquired all 3D images at a minimum of 22 frames per second and excluded from analysis all images that had poor tracking of greater than 3 myocardial segments, dropout of the apex, or stitch artifact. Two readers used a vendor-independent analysis platform (TomTec Cardiac Performance Analyses, Unterschleissheim, Germany) to measure 3D LVEF and the following 3D deformation parameters: principal strain, global longitudinal strain (GLS), global circumferential strain (GCS), and left ventricular torsion. Spearman correlation analyses were performed to understand the relationships amongst these parameters. Results: We analyzed 270 total echocardiograms from 87 women (mean age 49). Conventional 3D strain parameters were highly correlated with 3D LVEF (principal strain, r=-0.95, p&lt;0.001; GLS, r=-0.85, p&lt;0.001; GCS r=-0.97, p&lt;0.001). In contrast, left ventricular torsion was only modestly correlated with 3D LVEF (r=0.51, p&lt;0.001). Conclusions: Three dimensional principal strain, GLS, and GCS were all strongly correlated with 3D LVEF. However, left ventricular torsion was only weakly correlated to LVEF, suggesting that LVEF is determined less by torsion than by 3D strain. With further study, 3D strain may play an important role in chemotherapy cardiotoxicity risk prediction.
Automatic Border Detection Identifies Subclinical Anthracycline Cardiotoxicity in Children With Malignancy
Authors: IkuoHashimoto, FukikoIchida, MasayoshiMiura, TakashiOkabe, HirokazuKanegane, Kei-ichiroUese, YujiHamamichi, TakuroMisaki, ShoichiKoizumi, ToshioMiyawaki
Journal: Circulation (1999)

Background—Anthracycline drugs for cancer therapy often cause functional myocardial impairment even in relatively low doses. We investigated the left ventricular function in asymptomatic anthracycline-treated children by automatic border detection (ABD) to assess its clinical usefulness for unmasking latent anthracycline-induced myocardial damage. Methods and Results—Thirty-four children (0.7 to 17.6 years old) during or after anthracycline chemotherapy (26 to 1100 mg/m2) for malignancy (Chemo group) were studied, and 40 children (2.8 to 15.6 years old) without cardiac involvement served as normal control subjects (Control group). All patients underwent complete echocardiographic examination, including M-mode, Doppler, and ABD. Conventional echocardiography disclosed no difference between groups with regard to ejection fraction and the ratio of early to late transmitral flow velocity. In marked contrast, an investigation using ABD revealed that the Chemo group appeared to have some anthracycline-induced m...
Abstract 5123: Changes of oral microbiome profiles associated with oral squamous cell carcinoma
Authors: Kengo Hashimoto, Shuji Nomoto, Sho Hirabayashi, Sei Ueda, Ichiro Oh-iwa, Toru Nagao, Kazuo Shimozato
Journal: Cancer Research (2018)

Abstract [Background] Oral squamous cell carcinoma (OSCC) is the most frequently occurring cancer among the head and neck SCCs worldwide. Despite significant efforts in OSCC research and advanced surgical treatments, radiotherapy, and chemotherapy, the 5-year overall survival rate has remained &amp;lt; 50% for the last few decades. OSCC prognosis remains poor due to late diagnosis. Therefore, clinically effective biomarkers for the early detection of OSCC can greatly improve the survival rate and prognosis. Approximately 15% of oral cancers cannot be explained by major risk factors, such as tobacco and alcohol use. A growing body of evidence supports an association between specific microorganisms, including those in the oral cavity, and various types of cancers. Because the role of bacteria in OSCC development has not been completely described, we investigated the changes in abundance of oral microbiota associated with OSCC. [AIMS] To identify the association between the oral microbiome and OSCC for the early detection and prevention. [Materials and methods] Unstimulated saliva samples were collected from 4 OSCC-free, 6 leukoplakia, and 6 OSCC subjects. Total bacterial genomic DNA from saliva was isolated, and 16S rRNA gene survey was performed by next-generation sequencing of the V4 region. The sequences were analyzed against reference sequences from the Human Oral Microbiome Database, and the relative abundance distribution for phylogenetic groups in 3 different libraries was compared. [Results] In total, 448 bacterial species from combined (OSCC-free, leukoplakia, and OSCC) libraries were detected, which were classified into 133 genera, 69 families, 41 orders, 26 classes, and 12 phyla. The frequency of phylum Bacteroidetes was more notably abundant in OSCC subjects compared with leukoplakia and OSCC-free subjects. In contrast, the abundances of genera Streptococcus and Rothia were significantly lower in OSCC subjects compared with leukoplakia and OSCC-free subjects using the Mann-Whitney U test. [Conclusion] This study revealed some OSCC-associated shifts in oral microbial communities. Salivary screening is suitable for the primary screening procedure because of its noninvasiveness and easy accessibility. Therefore, these changes in the saliva microbiome may have potential application as a useful diagnostic tool for the early detection of OSCC and malignant transformation of pre-cancerous regions. Citation Format: Kengo Hashimoto, Shuji Nomoto, Sho Hirabayashi, Sei Ueda, Ichiro Oh-iwa, Toru Nagao, Kazuo Shimozato. Changes of oral microbiome profiles associated with oral squamous cell 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 5123.
Functional Cooperation Between Smad Proteins and Activator Protein-1 Regulates Transforming Growth Factor-β–Mediated Induction of Endothelin-1 Expression
Authors: FernandoRodríguez-Pascual, MarianoRedondo-Horcajo, SantiagoLamas
Journal: Circulation Research (2003)

Endothelin-1 (ET-1) is a 21–amino-acid potent vasoconstrictor peptide that is mainly produced by vascular endothelial cells. Expression of the ET-1 gene is subject to complex regulation by numerous factors, among which transforming growth factor-β (TGF-β) is one of the most important. It has been widely documented that TGF-β increases ET-1 mRNA and peptide levels. We have explored the mechanism by which TGF-β upregulates ET-1 expression in endothelial cells. Transcriptional activation of the ET-1 promoter accounted for the TGF-β–induced increase in ET-1 mRNA levels. We have identified within the ET-1 promoter two DNA elements indispensable for TGF-β–mediated induction of ET-1: an activator protein-1 (AP-1) site at −108/−102, known to be important for constitutive and induced expression, and a novel regulatory sequence located at −193/−171, which constitutes a specific binding site for Smad transcription factors. Mutation of both elements abolished TGF-β responsiveness. Binding of Smad3/Smad4 and c-Jun to ...
Studies of Quantitative Ballistocardiography
Authors: Vincenzomasini, Paolorossi
Journal: Circulation (1953)

The speed of body displacement was calculated on 70 per cent of the ballistocardiograms recorded in 128 patients suffering from heart disease. Results show that the values are generally lower in cardliac patients than in normal subjects, with the exception of cases with high stroke volume. The diminution of the speed of body displacement is proportional to the severity of ballistic abnormalities and to the functional state of the heart. A tentative explanation of the findings is presented.