tbuckley/cabot-search huggingface dataset:
Comparison of Cardiopulmonary Adaptation During Exercise in Children After the Atriopulmonary and Total Cavopulmonary Connection Fontan Procedures
Authors: MarkRosenthal, AndrewBush, JohnDeanfield, AndrewRedington
Journal: Circulation (1995)

Background There are several potential physiological differences between the atriopulmonary (AP) and the total cavopulmonary connection (TCPC) Fontan circulations. Studies suggest that the TCPC reduces energy loss due to turbulence and may have more dependence on respiratory movement for pulmonary blood flow. We compared cardiopulmonary physiology during rest and exercise in patients who had undergone the AP Fontan procedure with those who had undergone the TCPC Fontan procedure. Methods and Results Forty-three children were studied more than 6 months after undergoing a Fontan procedure (23 AP and 20 TCPC); 106 healthy children were also studied as a control group. Measurements of effective pulmonary blood flow, stroke volume, arteriovenous oxygen difference, minute ventilation, heart rate, and oxygen and carbon dioxide consumption were made with an Innovision quadrupole mass spectrometer. Data from the control group allowed calculation of z scores for the Fontan groups matched for age, sex, pubertal stag...
Abstract 2168: Anti-cancer drug sensitivity assay using in vitro primary culture cells
Authors: Shiki Fujino, Norikatsu Miyoshi, Masayuki Ohue, Kazuhiro Saso, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
Journal: Cancer Research (2018)

Abstract Primary culture of cancer cells derived from an individual patient's tumor provides important information regarding the tumor character. We established a novel culture method for primary colorectal cancer (CRC) with phenotypic heterogeneity as a human tumor model, named isolated tumor-derived cancer cells (iCCs). The success rate of iCC growth in vitro was 100%, passage was 90%, and establishment of a xenograft model from iCC was 80%. The gene expression of the cultured cells was similar to the clinical tumors, and exhibited a ductal structure of the tumor in the xenograft model even after several passages. The present in vitro analyses allow us to predict the clinical efficacy of chemotherapeutic drugs. For this purpose, we examined the sensitivities of iCCs isolated from patients. In this study four patients with distant metastasis received FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) chemotherapy according to the treatment guidelines, and in vitro drug sensitivity was evaluated using the cultured cells, compared with each parental tumor in the individual clinical course. It is a model to predict the effect of chemotherapy to the individual tumor. Our results showed that the effect of chemotherapy was poor in three patients and good in one patient. In their clinical courses, the tumor size increased in two patients and decreased in two patients. In vitro drug sensitivity results reflected the clinical course in three of the four patients. In conclusion, our primary culture model is a novel tool for the prediction of anti-cancer drugs in the clinical courses. Citation Format: Shiki Fujino, Norikatsu Miyoshi, Masayuki Ohue, Kazuhiro Saso, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori. Anti-cancer drug sensitivity assay using in vitro primary culture cells [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 2168.
Abstract 4853: Regulation of proteolytic repair of Top2 covalent complexes
Authors: Yilun Sun, Karin C. Nitiss, John L. Nitiss
Journal: Cancer Research (2018)

Abstract DNA topoisomerases (topos) play an essential role in nuclear processes such as replication, transcription, and chromosome segregation. These enzymes regulate DNA topology by introducing transient breaks in DNA with formation of transient protein/DNA covalent complexes. These complexes can be trapped by aberrant DNA structures, and are also the basis for anti-cancer drugs that target topos. Since topos can be trapped on DNA, leading to strand breaks with protein adducts at the site of the breaks, cells require DNA repair pathways to process protein adducts. We have examined the repair of the type II topos (Top2) in yeast and mammalian cells. We developed a sensitive assay to detect ubiquitylation and other post-translational modifications (PTMs) of Top2 trapped on DNA in S. cerevisiae and have shown that the proteasome plays a key role in repair of Top2 damage induced by the anti-cancer drug etoposide. We demonstrated that sumoylation of Top2 is induced by etoposide, and that deletion of the SUMO ligase Siz2 prevents etoposide induced sumoylation. Deletion of either of the genes encoding the ubiquitin ligase Slx5/Slx8 led to decreased ubiquitylation of trapped Top2. The mammalian ortholog of Slx5/Slx8 is Rnf4, and it too plays a role in ubiquitylation and degradation of Top2 trapped by etoposide. A human cell line completely lacking Rnf4 is defective in ubiquitylation of Top2β, one of the two mammalian Top2 isoforms. Interestingly, repair of the Top2α isoform is unaffected in an Rnf4 knockout cell line. Proteolysis of trapped Top2 is also subject to negative regulation. The UBA domain protein UBAP2L, (also termed NICE4) is amplified in various cancers. Knockout of the UBAP2L increases proteolysis of trapped Top2. Levels of trapped Top2α and Top2β are decreased in the absence of UBAP2L, and the level of trapped Top2 returns to the wild type level when MG132 is added, indicating UBAP2L regulates the proteasome mediated degradation of Top2. UBAP2L physically interacts with Top2β as determined by co-immunoprecipitation, and the interaction is not seen in Rnf4 knockout cells. Finally, knockout of UBAP2L confers high level resistance to etoposide. Our results provide insights to the response of cancer cells to Top2 targeting agents. Citation Format: Yilun Sun, Karin C. Nitiss, John L. Nitiss. Regulation of proteolytic repair of Top2 covalent complexes [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 4853.
Abstract 2348: Low-cost and accurate human leukocyte antigen (HLA) class I typing of The Cancer Genome Atlas on the Seven Bridges Cancer Genomics Cloud
Authors: Raunaq Malhotra, Alexandar Krasnitz, Anurag Sethi, Erik Lehnert, Elizabeth H. Williams, Davis-Dusenbery N. Brandi
Journal: Cancer Research (2018)

Abstract The Cancer Genome Atlas (TCGA)network has generated more than2.5petabytes of genomic dataover the last decade, with petabyte-scale additions of dataexpected inthe coming years. Access and analysis of this informationonalocal compute environment is challenging due tothe volume of dataand lack of sufficient computing resources at many research organizations. The Cancer Genomics Cloud Pilot project from the National Cancer Institute (NCI)has helped indemocratizing access toTCGA by co-localizing datawith computational resources onthe cloud. Funded as part of this project, the SevenBridges Cancer Genomics Cloud (CGC)hosts nearly 5petabytes of public datafrom TCGA, the Simons Genome Diversity Project, the Therapeutically Applicable Research toGenerate Effective Treatments (TARGET)initiative, The Cancer Imaging Archive (TCIA), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The CGCprovides academic researchers with asecure, scalable, cloud-based cancer research platform that includes collaborative tools for accessing, uploading, analyzing, and visualizing data. The platform uses resource descriptionframeworks, dataharmonization, and metadatacurationtofacilitate effective querying, and bioinformatics tools are implemented onthe CGCusing the CommonWorkflow Language (CWL), an emerging standard for describing computational workflows, tosupport computational reproducibility. Since its launch in2016, the CGChas enabled researchers from around the world tounderstand humangenetics and cancer biology through the analysis of large public datasets and private datainacloud computing environment. Inthis poster, we present anexample of analysis of TCGAdataonthe CGC. The OptiType tool for HumanLeukocyte Antigenclass I typing was used toprofile 8,872RNA-Seq samples present inthe TCGAdataset. All samples were accurately processed within2days using arobust, fault-tolerant, and cost-efficient CWL descriptionof OptiType that enabled analysis for less than50cents per sample onaverage. This case study demonstrates how cloud computing resources canfacilitate the successful analysis of large cohorts of datausing custom pipelines in a robust, scalable, and reproducible manner. Citation Format: Raunaq Malhotra, Alexandar Krasnitz, Anurag Sethi, Erik Lehnert, Elizabeth H. Williams, Davis-Dusenbery N. Brandi. Low-cost and accurate human leukocyte antigen (HLA) class I typing of The Cancer Genome Atlas on the Seven Bridges Cancer Genomics Cloud [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 2348.
Abstract 314: A novel MDM2-p53 antagonist APG-115 induces p53-mediated apoptosis and enhances radiosensitivity in colorectal cancer
Authors: Han-Jie Yi, Xiang-Lei Yan, Qiu-Yun Luo, Luping Yuan, Baoxia Li, Wentao Pan, Lin Zhang, Miao-Zhen Qiu, Guangfeng Wang, Yifan Zhai, Da-Jun Yang
Journal: Cancer Research (2018)

Abstract Background: Colorectal carcinoma is the third leading cause of cancer-related mortality in China. MDM2-p53 inhibitor APG-115 is a novel potential anticancer agent. We aim to investigate the anticancer effect and radiosensitivity enhancement of APG-115 in colorectal cancer. Materials and methods: Human colorectal cancer cell lines (LOVO, HCT116, RKO, HT29, SW480 and SW620) were treated with the APG-115 alone or with radiation (0-8Gy). Transwell, clonogenic survival assays, CCK-8, flow cytometry, RT-qPCR, Western blot were used to assay cell invasion, cell survival, cell cycle progression, quantification of mRNA expression and DNA damage repair. In vivo, xenograft mouse models (RKO Cell line) were established to analyze the anticancer effect and radiosensitivity enhancement of APG-115. Results: In vitro, APG-115 not only inhibited invasion and proliferation of colorectal cell lines, but also induced cell-cycle arrest in G1/S phase. Meanwhile, APG-115 increased the mRNA and protein expression of p53 downstream targets dependent on MDM2-p53 signal pathway. The combination of APG-115 and radiation caused cells to accumulate in G2/M and resulted in the accumulation of H2AX-related DNA damage, indicating an increasing of radiosensitivity. In xenograft mouse models, single therapy with either radiation or APG-115 was equivalent in delaying tumor growth, although APG-115 slightly outperforming therapy with radiation alone. Combination therapy delayed tumor growth more significantly compared with either single agent therapy. By analyzing proliferation marker Ki67 in xenograft tumor specimens, we found that the number of proliferating cells significantly decreased in tumors receiving combination treatment of APG-115 and radiation compared with tumors receiving single agent treatment. These results strongly confirmed the enhanced antitumor capacity of APG-115 when combined with radiation. Conclusions: Our data strongly suggest that MDM2-p53 inhibitor APG-115 may serve not only as a stand-alone therapy, but also as an effective adjunct to current radiotherapeutic regimens for treating colorectal cancer dependent on MDM2-p53 axis. Citation Format: Han-Jie Yi, Xiang-Lei Yan, Qiu-Yun Luo, Luping Yuan, Baoxia Li, Wentao Pan, Lin Zhang, Miao-Zhen Qiu, Guangfeng Wang, Yifan Zhai, Da-Jun Yang. A novel MDM2-p53 antagonist APG-115 induces p53-mediated apoptosis and enhances radiosensitivity in colorectal 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 314.
Abstract 19312: Multiplexed Images of the Heart Provide Novel Functional Information to Guide Invasive Procedures: A Review of the Initial Case Series
Authors: Sabine Ernst, Richard S Underwood, Simona Ben-Haim
Journal: Circulation (2015)

Introduction: The novel, high sensitivity and dedicated cardiac camera (D-SPECT, Spectrum Dynamics) allows single or dual tracer studies to add functional information to 3D DICOM image information from CT or CMR. Information consists of either perfusion information (from (technetium-99m (Tc-99m) methoxyisobutylisonitrile (MIBI, for perfusion) and/or sympathetic nnervation information using meta-iodobenzylguanidine (mIBG). Merging these 3D images with invasive 3D electroanatomical maps (EAM) offers image integration on a function rather than geometrical level alone. These fused 3D images can be combined with EAM to guide ablation procedures for either atrial or ventricular arrhythmias. Methods: A total of 23 patients (15 male, mean age 59.9 yrs) underwent either single iodine-123 mIBG (n=10, for sympathetic innervation) or dual tracer (n= 13, mIBG+MIBI, for perfusion) imaging and the acquired information was fused with the 3D cCT or CMR using a custom-made software. Results: Twenty out of 23 patients underwent invasive electrophysiology studies which targeted either atrial or ventricular arrhythmias. During the atrial arrhythmia procedures, high uptake sites for mIBG was correlated to positive effect of high frequency stimulation (=transient prolongation of AV nodal conduction) and thereby confirming ganglionated plexi which were targeted in addition to the standard ablation. Patients with ventricular arrhythmia, low amplitude voltage mapping showed good correlation to the perfusion scar imaging, thereby serving as a substrate map even in patients with implantable devices. Interestingly, regions of mismatch where identified which proved to be pro-arrhythmogenic during EP study in the 4/6 patients who underwent ventricular tachycardia (VT) ablation. Conclusion: The combination of innervation (by mIBG) and perfusion (by MIBI) nuclear imaging in addition to the 3D cCT or CMR imaging provides a novel type of “road map” information for complex arrhythmia ablation by providing a region of mismatch of innervation and perfusion. This provides a novel substrate information even in the presence of implantable devices.
Abstract 5411: Micro-RNA expression in cemento-ossifying fibroma
Authors: Thais S. Pereira, André Luiz S. Guimarães, Carolina C. Gomes, Ricardo S. Gomez, Marina G. Diniz
Journal: Cancer Research (2018)

Abstract Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis and its treatment is associated with significant morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis. Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan® OpenArray® Human MicroRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath. Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p, hsa-miR-200c-3p) and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138-5p, hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant Kegg-pathways revealed by enrichment analysis were Proteoglycans in cancer, miRNAs in cancer, Pathways in cancer, p53, PI3K-Akt, FoxO, and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis. Dysregulation of miRNAs occurs in COF and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation. Supported by: CNPq, CAPES and FAPEMIG (Brazil). Citation Format: Thais S. Pereira, André Luiz S. Guimarães, Carolina C. Gomes, Ricardo S. Gomez, Marina G. Diniz. Micro-RNA expression in cemento-ossifying fibroma [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 5411.
Dissemination of Chest Compression–Only Cardiopulmonary Resuscitation and Survival After Out-of-Hospital Cardiac Arrest
Authors: TakuIwami, TetsuhisaKitamura, KosukeKiyohara, TakashiKawamura
Journal: Circulation (2015)

Background—The best cardiopulmonary resuscitation (CPR) technique for survival after out-of-hospital cardiac arrests (OHCAs) has been intensively discussed in the recent few years. However, most analyses focused on comparison at the individual level. How well the dissemination of bystander-initiated chest compression–only CPR (CCCPR) increases survival after OHCAs at the population level remains unclear. We therefore evaluated the impact of nationwide dissemination of bystander-initiated CCCPR on survival after OHCA. Methods and Results—A nationwide, prospective, population-based, observational study covering the whole population of Japan and involving consecutive OHCA patients with resuscitation attempts was conducted from January 2005 through December 2012. The main outcome measure was 1-month survival with favorable neurological outcome. The incidence of survival with favorable neurological outcome attributed to types of bystander CPR (CCCPR and conventional CPR with rescue breathing) was estimated. Am...
Acute Effects of Countershock Conversion of Atrial Fibrillation upon Right and Left Heart Hemodynamics
Authors: Attilioreale
Journal: Circulation (1965)

Right and left heart hemodynamics were studied in 12 patients with mitral valvular disease and atrial fibrillation before and immediately after external direct-current countershock resulting in restoration of normal sinus rhythm. The change of rhythm was accompanied by the following hemodynamic variations in the majority of cases: Systolic and mean pressures in the right and left ventricles and in the pulmonary and brachial arteries were not systematically altered, with a tendency, however, to a decrease in ejection pressures in the right heart and increase in the left heart. Mean right atrial and right ventricular end-diastolic pressures as well as left ventricular end-diastolic pressure decreased significantly. The behavior of the mean left atrial pressure appeared to be influenced by the degree of mitral valvular disease. Cardiac output and index and stroke volume and index increased; pulmonary vascular and systemic resistances decreased. The stroke work of the ventricles also increased in the majority...
Thyroid Hormone Targets Matrix Gla Protein Gene Associated With Vascular Smooth Muscle Calcification
Authors: YojiSato, RyoNakamura, MitsutoshiSatoh, KayokoFujishita, SatokoMori, SeiichiIshida, TeruhideYamaguchi, KazuhideInoue, TakuNagao, YasuoOhno
Journal: Circulation Research (2005)

Thyroid hormones have marked cardiovascular effects in vivo. However, their direct effects on vascular smooth muscle cells have been unclear. Because thyroid hormones play critical roles in bone remodeling, we hypothesized that they are also associated with vascular smooth muscle calcification, one of the pathological features of vascular sclerosis. To test this hypothesis, we examined the effects of 3′,3,5-triiodo-l-thyronine (T3) on the expression of calcification-associated genes in rat aortic smooth muscle cells (RAOSMCs). Quantitative RT-PCRs revealed that a physiological concentration of T3 (15 pmol/L free T3) increased mRNA level of matrix Gla protein (MGP), which acts as a potent inhibitor of vascular calcification in vivo, by 3-fold in RAOSMCs, as well as in cultured human coronary artery smooth muscle cells. In RAOSMCs transiently transfected with a luciferase reporter gene driven by the MGP promoter, T3 significantly stimulated luciferase activity. In addition, RNA interference against thyroid ...
Abstract 5906: EGFR and SOX2 crosstalk determines EGFR-TKI
Authors: An-Chun Lee, Chia-Cherng Yu, Yuan-Hung Wang, Yu-Ting Chou
Journal: Cancer Research (2018)

Abstract Activating mutations in the epidermal growth factor receptor (EGFR), while initiating lung tumorigenesis, render tumors susceptible to EGFR-tyrosine kinase inhibitors (TKIs). SOX2 functions as a cell fate determination factor in lung progenitor cells. However, how SOX2 expression affects TKI treatment and tumor invasion in lung cancer is obscure. Here we report that EGFR mutations crosstalk with SOX2 to maintain cell proliferation and barrier properties in lung cancer cells, some of which generate heterogeneity by switching off SOX2 expression, thus promoting TKI resistance and invasiveness. Downregulation of SOX2 expression by shRNA against SOX2 or TGF-beta treatment induced epithelial-to-mesenchymal transition (EMT) and endowed cell resistant to TKIs. TKI treatment selected EGFR-mutated lung cancer cells harboring low SOX2 expression with the EMT signature. TKI naïve EGFR-mutated lung cancer cells harboring low SOX2 expression exhibits intrinsic TKI resistance. Conversely, enhancing endogenous SOX2 expression reverses EMT and increases sensitivity to TKIs. Immunohistochemistry analysis revealed that low SOX2 expression predicts a poor survival in patients harboring EGFR mutations. Taken together, our findings show how cancer plasticity elicited by SOX2 expression and TKI selection generates distinct oncogenic properties and TKI sensitivity, providing critical insights into tumor progression in EGFR-mutated lung cancer. Citation Format: An-Chun Lee, Chia-Cherng Yu, Yuan-Hung Wang, Yu-Ting Chou. EGFR and SOX2 crosstalk determines EGFR-TKI [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 5906.