tbuckley/cabot-search huggingface dataset:
Abstract 19653: Therapeutic Potential of Long Ultrasound Tone Bursts in Microbubble-Ultrasound Mediated Therapeutics: Mechanistic Insights Using High Speed Imaging
Authors: Jianjun Wang, Xucai Chen, John Pacella, Flordeliza Villanueva
Journal: Circulation (2012)

Background: Microbubble (MB)-Ultrasound (US) assisted therapy has been shown to restore perfusion in myocardial infarction (sonothrombolysis). Due to a presumption that MBs under high acoustic pressure do not persist after long acoustic cycles, most schemes of US-assisted therapy utilize a very short US pulse (a few acoustic cycles) when a high US pressure is used. However, we have recently observed enhanced in vitro sonothrombolytic effect using MBs and very long US pulses, at high acoustic pressures. We therefore sought to explore the actual fate of MBs during a long acoustic cycle exposure by visual observation of MB acoustic behaviors at varying pulse lengths. Methods: MB behaviors were optically observed during long US tone burst excitation using an ultra-high speed imaging system that allows microscopic visualization of MB cavitation. The system is capable of capturing 128 frames at up to 25 million frames per second (Mfps). Long US tone bursts (up to 5,000 acoustic cycles) at 1 MHz and various pressures (0.25, 0.5, 1.0, and 1.5 MPa) were used to study the dynamic behavior of both lipid and polymer MBs in a 200-µm diameter cellulose tubing. Results: High speed movies of the MBs during long tone burst excitation showed that MBs first underwent inertial cavitation then formed gas-filled aggregates that continued to oscillate. The locations of the aggregates were random due to the dynamic nature of MB destruction. Figure 1 shows still frames of a high speed movie (5 Mpfs) of polymer MBs 1,000 acoustic cycles into a long tone burst at 1.5 MPa: MB aggregates continued to oscillate, break up, and new aggregates were formed. Conclusion: These data show for the first time that MBs survive as aggregates that continue to oscillate with large amplitude during a long tone burst, demonstrating the therapeutic potential for US-assisted therapy. This discovery suggests that long acoustic cycles have additional therapeutic effect for MB-US assisted therapies such as sonothrombolysis.
The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization
Authors: Jana Mehlich, Jörg Fischer, Christiane Hilger, Kyra Swiontek, Martine Morisset, Françoise Codreanu-Morel, Maximilian Schiener, Simon Blank, Markus Ollert, Ulf Darsow, Tilo Biedermann, Bernadette Eberlein
Journal: Journal of Allergy and Clinical Immunology (2018)
Prerequisite for Cardiac Aldosterone Action
Authors: MarcLombès, NadiaAlfaidy, EmmanuelEugene, AlessandroLessana, NicoletteFarman, Jean-PierreBonvalet
Journal: Circulation (1995)

Background It has been proposed that aldosterone exerts direct effects on heart function, most notably on the development of myocardial fibrosis during ventricular hypertrophy in rat. Initial events in aldosterone action entail its binding to mineralocorticoid receptor (MR). Because MR displays similar affinities for aldosterone and glucocorticoids, the in vivo aldosterone selectivity of MR requires the presence of an enzyme, 11β-hydroxysteroid dehydrogenase (11-HSD), which metabolizes glucocorticoids into inactive derivatives. Although evidence exists for the presence of MR in rodent heart, no data are available for humans; moreover, the existence of cardiac 11-HSD is controversial. Methods and Results The heart samples used originated from tissue removed during cardiac surgery in nontransplant patients or from endocavitary biopsies done for the follow-up of heart transplantation. The expression of MR was examined at the mRNA and protein level by in situ hybridization with cRNA probes specific for human ...
Abstract 17788: Impact of an Invasive Strategy on In-Hospital Outcomes in Nonagenarians With Acute Coronary Syndrome: Insights From the AMI-OPTIMA Study
Authors: Etienne L Couture, Paul Farand, Michel Nguyen, Catherine Allard, Jonathan Afilalo, Marc Afilalo, Erick Schampaert, Mark Eisenberg, Martine Montigny, Samer Mansour, Simon Kouz, Claude Lauzon, Jean-Claude Tardif, Thao Huynh
Journal: Circulation (2016)

Background: Nonagerians constitute a growing proportion of patients with acute coronary syndromes (ACS). Currently, little is known about their characteristics, prognosis and optimal management. We...
Abstract 20983: Size Based Microfluidic Enrichment of Human Inducedpluripotent Cell-derived Cardiomyocytes
Authors: Mahdokht Masaeli, Alexandre Ribeiro, Li-Chun Lin, Alex Dainis, Euan Ashley, Beth Pruitt
Journal: Circulation (2016)

While human induced pluripotent stem cell (iPSC)-derived CMs offer a tantalizing cellular model for drug discovery and understanding mechanisms underlying heart disease, current protocols yield highly heterogeneous populations [1,2]. The heterogeneity in iPSC-CM cultures suggests variation in the maturation, which has been correlated with cell size and shape [3-5]. This study offers a novel approach to enrich structurally mature-like iPSC-CMs, which would also address current inaccuracies in the assessment of properties of iPSC-CM cultures due to the cell-to-cell variations. We have used inertial microfluidics and have shown the feasibility of sorting live iPSC-CMs based on size and shape. Materials and Methods: Cells were differentiated using previously described methods and cultured on Matrigel-coated dishes. iPSC-CMs were then re-suspended in RPMI media at 2-5x105 cells/mL density. After passing through the microfluidic chip (Fig. 1A) at 60μL/min [6], sorted cells were either collected for RNA extracti...
Abstract 2027: P62/IMP2 promotes metastasis in hepatocellular carcinoma (HCC) by regulating EMT in different signaling pathway
Authors: Mengtao Xing, Jianxiang Shi, Jitian Li, Beibei Chen, Giulio Francia, Jianying Zhang
Journal: Cancer Research (2018)

Abstract Insulin- like growth factor 2 mRNA binding proteins (IMPs) Family contains three members: IMP1, IMP2 and IMP3. IMPs are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. Overexpressed IMPs have been reported in various types of cancers. They share similar protein structure in mammals and have similar functions: to bind specific mRNAs, stabilize and extend their half-life. IMP2 was first reported as a tumor-associated antigen in HCC. However, only a few research was done on what a role of p62/IMP2 plays on HCC progression. Previous studies show that IMP2 is overexpressed in HCC tissues and in several human HCC cell lines. Western blotting was performed for different HCC cells has a relatively low expression in SNU449 and higher expression in HepG2 and Hep3b. Stable IMP2 overexpression SNU449 cell line was made by IMP2 cDNA plasmid transfection; stable IMP2 knockout Hep3b and HepG2 cell lines was made by IMP2 Crispr-Cas9 KO plasmid transfection. Wound healing assay has shown that overexpression of p62/IMP2 can significantly enhance cell migration ability in SNU449 cells. On the contrary, the depletion of p62/IMP2 can reduce the migration ability in HepG2 and Hep3b cells (p&amp;lt;0.05). Furthermore, we analyzed HCC gene expression data from TCGA. Median count of IMP2 was used to separate HCC expression data into high and low IMP2 expression group to conduct differential gene expression analysis. Gene Ontology over-representation analysis shows differentially expressed genes (adjusted p&amp;lt;0.05) mainly enriched in membrane part and plasma membrane. The expression of several genes involved in EMT regulation such as CTNNB1, SMAD2, SNAI2, AKT2 shows significant difference (adjust p&amp;lt;0.05). Western blotting assay was performed to show whether IMP2 is involved in EMT regulation. Wnt/beta-catenin pathway and TGF-beta/SMAD pathway were both activated and further upregulated SNAIL, which is an E-cadherin inhibitor. Western blotting results showed that E-cadherin was inhibited in IMP2 overexpressed SNU449 cells, which is supportive to our hypothesis. Citation Format: Mengtao Xing, Jianxiang Shi, Jitian Li, Beibei Chen, Giulio Francia, Jianying Zhang. P62/IMP2 promotes metastasis in hepatocellular carcinoma (HCC) by regulating EMT in different signaling 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 2027.
Early Appearance of an Edematous Tissue Reaction During Left Atrial Linear Ablation Using Intracardiac Echo Imaging
Authors: RukshenWeerasooriya, PierreJaïs, PrashanthanSanders, ChristopheScavée, Li-FernHsu, MélèzeHocini, JacquesClementy, MichelHaïssaguerre
Journal: Circulation (2003)
Association of In Utero Exposure to Polybrominated Diphenyl Ethers With the Risk of Hypospadias
Authors: Shirley Poon, Gideon Koren, Amanda Carnevale, Katarina Aleksa, Juejing Ling, Jak Ozsarfati, Bhushan M. Kapur, Darius Bagli
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Polybrominated diphenyl ethers (PBDEs) are added to many consumer products as flame retardants, and their endocrine-disrupting properties are a growing health concern in pregnancy. <h3>Objective</h3> To investigate whether in utero PBDE exposure as measured in maternal hair is associated with increased risk for hypospadias. <h3>Design, Setting, and Participants</h3> In this case-control study, the setting was the urology clinic of a tertiary pediatric hospital between January 3, 2011, and April 1, 2013. Participants were children diagnosed as having hypospadias and their mothers and a control group of children without hypospadias and their mothers. Dates of data analysis were September 3, 2017, to December 28, 2017. <h3>Exposures</h3> Gestational exposure to 8 PBDEs as measured in the 3-cm segment closest to the skull of maternal hair by gas chromatography–mass spectroscopy as a proxy for in utero exposure. The mothers resided in the same household for the duration of their pregnancy. <h3>Main Outcomes and Measures</h3> Difference in total maternal hair PBDE levels between the hypospadias and control groups. <h3>Results</h3> Total PBDE levels were significantly higher among mothers of infants with hypospadias (n = 152) (total PBDE level, 51.4 pg/mg; interquartile range, 35.8-78.5 pg/mg) than among controls (n = 64) (total PBDE level, 35.8 pg/mg; interquartile range, 18.1-69.9 pg/mg) (<i>P</i> = .02). Of the 152 women with sufficient hair samples for analysis in the case group, 89 completed a questionnaire and were included in a multivariable analysis, and of the 64 women with sufficient hair samples for analysis in the control group, 54 completed a questionnaire and were included in a multivariable analysis. Adjusting for potential confounders, hypospadias was associated with a relative 48.2% (95% CI, 23.2%-65.4%) higher maternal level of total PBDE levels in the multivariable analysis. <h3>Conclusions and Relevance</h3> In this analysis, mothers of children with hypospadias were exposed during pregnancy to significantly higher levels of PBDEs. The results of this study suggest that level of exposure to PBDEs during gestation may have a role in the etiology of hypospadias.
Getting to the Heart of the Matter
Authors: AndrewLeask
Journal: Circulation Research (2015)

Fibrotic diseases are a significant global burden for which there are limited treatment options. The effector cells of fibrosis are activated fibroblasts called myofibroblasts, a highly contractile cell type characterized by the appearance of α-smooth muscle actin stress fibers. The underlying mechanism behind myofibroblast differentiation and persistence has been under much investigation and is known to involve a complex signaling network involving transforming growth factor-β, endothelin-1, angiotensin II, CCN2 (connective tissue growth factor), and platelet-derived growth factor. This review addresses the contribution of these signaling molecules to cardiac fibrosis.
Preventing Venous Thromboembolism in Medical Patients
Authors: AlainLeizorovicz, PatrickMismetti
Journal: Circulation (2004)

Given the increased number of patients hospitalized for acute medical illnesses and the associated risk of venous thromboembolism (VTE), the use of prophylaxis has become a public health matter. Thromboprophylaxis is not widely practiced in acutely ill medical patients, due in part to the heterogeneity of this group and the perceived difficulty in assessing those who would most benefit from treatment. Nevertheless, the results of recent well-conducted clinical trials support the evidence-based recommendations for more widespread systematic use of low-dose low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in this population. Three large well-controlled studies (MEDENOX, PREVENT, and ARTEMIS) in acutely ill medical patients confirm previous findings that different at-risk patient populations show a consistent 50% reduction in VTE events with LMWH and fondaparinux. A meta-analysis in nearly 5000 patients in internal medicine comparing UFH and LMWH revealed a trend for reduction of deep vein...
Abstract 1924: Role of CXCL16 and ADAM10 in ovarian cancer pathogenesis
Authors: Hina Mir, Neeraj Kapur, James W. Lillard, Shailesh Singh
Journal: Cancer Research (2018)

Abstract Ovarian cancer is the leading cause of death from gynecological malignancies. The five-year survival rate of ovarian cancer ranges from 30 to 92%, depending on the severity of the disease. Our laboratory has shown the role of chemokines and chemokines receptors in cancer, including ovarian cancer. In this study, we have shown higher expression of CXCR6, which is the only receptor of chemokine CXCL16, in ovarian cancer cell lines and clinical samples. We have tested the biological significance of CXCR6 and soluble CXCL16 (sCXCL16) using ovarian cancer cell lines in vitro. We show higher migratory and invasive potential of high CXCR6 expressing ovarian cancer cell lines in the response of sCXCL16. Migratory and invasive potential in response to sCXCL16 was significantly inhibited when CXCR6 and CXCL16 interaction was blocked using anti-CXCR6 monoclonal antibody. ADAM10 basal mRNA level was higher in cells with high migratory and invasive potential. Similar to cell lines, higher expression of CXCR6 and CXCL16, as well as ADAM10, was observed in tissue, which showed a positive correlation with tumor stage. These results suggest the clinical and biological significance of CXCR6-CXCL16 axis in the pathogenesis of ovarian cancer. Therefore, therapeutics directed to the CXCR6-CXCL16 axis may provide better therapeutic outcome and overall survival. Citation Format: Hina Mir, Neeraj Kapur, James W. Lillard, Shailesh Singh. Role of CXCL16 and ADAM10 in ovarian cancer pathogenesis [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 1924.
Abstract 4203: Alpha 9 nicotinic acetylcholine receptor promotes tumor progression in triple negative breast cancer
Authors: Yung-Che Kuo, Jan-Show Chu, Kha-Liang Lee, Hsiao-Feng Wang, Victor James Drew, Wei-Zhan Zhuang, Chi-Long Chen, Yuan-Soon Ho, Yen-Hua Huang
Journal: Cancer Research (2018)

Abstract Purpose: To assess the potential therapeutic target on the alpha 9 nicotinic acetylcholine receptor (α9-nAChR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR) for preventing distant metastasis in TNBC patients. Experimental Design: Expression levels of stemness-related genes, α9-nAChR and IGF-IR in clinical tissues (n = 67) were analyzed by RT-qPCR and the Pearson correlation analysis. The α9-nAChR, OCT4, IGF-1R, and p-IGF-1R protein in tissues were detected by immunohistochemical staining (n = 200). The effects of either α9-nAChR activation or IGF-1R transactivation on stemness expression in TNBC were examined using Western blot, ALDH activity assay with flow cytometry, shRNA silencing, wound closure/migration/invasion assay, as well as microCT scanning and IVIS assay for animal models. Results: A high positive correlation between the gene expression levels of OCT4/NANOG/CD24/CD44 and α9-nAChR/IGF-IR in human breast cancer tissues was observed. IGF-1R and OCT4 highly expressed in tumor part compared than that of in normal part. Moreover, IGF-1R positively correlated with OCT4 in tumor tissues. We also show that nicotine induced α9-nAChR activation trans-activates the expression of IGF-1R and pluripotent protein OCT4, which mediated stemness-related properties in TNBC cell lines. Our results reveal that knockdown α9nAChR and IGF-1R diminish the pernicious effects of nicotine, inhibit stemness activities, and suppress metastasis both in vitro and in vivo. Conclusions: A crosstalk between α9-nAChR and IGF-IR signal mediates the stemness-related properties and metastasis therefore convene poor prognosis in TNBCs. Citation Format: Yung-Che Kuo, Jan-Show Chu, Kha-Liang Lee, Hsiao-Feng Wang, Victor James Drew, Wei-Zhan Zhuang, Chi-Long Chen, Yuan-Soon Ho, Yen-Hua Huang. Alpha 9 nicotinic acetylcholine receptor promotes tumor progression in 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 4203.
The long non-coding RNA CYTOR drives colorectal cancer progression by interacting with NCL and Sam68
Authors: Xue Wang, Hongfei Yu, Wenjie Sun, Jianlu Kong, Lei Zhang, Jinlong Tang, Jingyu Wang, Enping Xu, Maode Lai, Honghe Zhang
Journal: Molecular Cancer (2018)

Long non-coding RNAs (lncRNAs) function as key molecules in cancer progression. The lncRNA CYTOR plays oncogenic roles in multiple types of cancer, yet the detailed molecular mechanisms of those roles remain unknown. The aim of this study was to investigate the clinical significance, biological function and interacting partners of CYTOR in colorectal cancer (CRC).A systematic and comprehensive analysis of CYTOR expression was performed in 138 CRC samples and in the TCGA and GEO databases. Biological function was investigated through knockdown and overexpression of CYTOR in vitro and in vivo. In addition, its protein binding partner was identified and validated using ChIRP-MS and RNA immunoprecipitation assays. Their key interaction sites on CYTOR were verified by CRISPR/Cas9 and a series of mutant constructs. Furthermore, the downstream targets of CYTOR were confirmed via immunoblotting and luciferase reporter assays.CYTOR was significantly up-regulated in CRC samples and associated with poor prognosis, promoting proliferation and metastasis in vitro and in vivo. NCL and Sam68 could recognize their specific motifs and directly bind to EXON1 of CYTOR. Moreover, EXON1 was the key functional site mediating the interaction of CYTOR with NCL and Sam68. NCL and Sam68 functioned as oncogenes to promote CRC progression. Furthermore, we confirmed that the heterotrimeric complex of CYTOR, NCL and Sam68 activated the NF-κB pathway and EMT to contribute to CRC progression.CYTOR plays important roles in CRC progression by interacting with NCL and Sam68 and may serve as a prognostic biomarker and/or an effective target for CRC therapies.
End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators
Authors: RQMigrino, JBYoung, SGEllis, HDWhite, CFLundergan, DPMiller, CBGranger, AMRoss, RMCaliff, EJTopol
Journal: Circulation (1997)

BACKGROUND: Left ventricular remodeling is an important sequela of myocardial infarction (MI). Although remodeling occurs soon after MI, the effect of early left ventricular dilatation on outcome is not established and may be useful for early risk stratification. We assessed whether end-systolic volume index (ESVI) at 90 to 180 minutes into thrombolytic therapy for MI is associated with adverse outcomes. METHODS AND RESULTS: In the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I study, 41021 patients with evolving MI received one of four thrombolytic regimens. At 90 or 180 minutes into reperfusion therapy, 1300 patients underwent left ventriculography. ESVI was measured and correlated with adverse outcomes: 30-day and 1-year mortality and in-hospital congestive heart failure, shock, and reinfarction. Clinical variables were also tested in a stepwise logistic regression analysis to determine predictors of left ventricular dilatation. ESVI was directly related to all ad...
Abstract 4835: UD-017, a novel highly selective and orally active CDK7 inhibitor, shows a significant anticancer activity in patient-derived cancers
Authors: Takashi Matsushita, Sayaka Ogi, Kazuhiro Onuma, Hidetoshi Sunamoto, Ayumi Ogawa, Toru Hasegawa, Yasunori Tokunaga, Yasuhiro Aga, Shigeru Ushiyama
Journal: Cancer Research (2018)

Abstract Background: Cyclin dependent kinase 7 (CDK7) is an attractive target for anticancer drugs due to its dual roles, cell cycle regulation and gene transcription/RNA processing. We synthesized UD-017, a small-molecule, highly selective, orally active CDK7 inhibitor with a novel chemotype. In this study, we characterized anticancer activities of UD-017 in vitro and in vivo using patient-derived (PD) cancer cells. Methods: We first evaluated an antiproliferative activity of UD-017 broadly in a panel of cancer cell assay including patient-derived 3-dimensional tumor clonogenic assay. To verify the potential of c-Myc expression as a biomarker, we investigated the correlation between c-Myc expression levels and anticancer activity in vitro and in vivo using a colorectal cancer cell. In the main part, anticancer efficacy of UD-017 was investigated in vivo in PD-xenograft (PDX) models using representative PD cancer cells. Results: In antiproliferative panel assays using over 100 cancer cell lines, UD-017 broadly inhibited a wide range of cancer cells from colon, breast, lung, kidney, blood, pancreas, osteosarcoma, sarcoma and urinary bladder cancers. Especially, UD-017 showed high sensitivity in solid tumor such as non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric, osteosarcoma and sarcoma cells with IC50s of 10-200 nM. UD-017 showed a good correlation of c-Myc expression levels with antiproliferative activity using colorectal cancer cells in vitro, and UD-017 reduced the intratumoral MYC mRNA levels by an administration at 100 mg/kg in a HCT-116 xenograft model in mice. In PDX models, UD-017 showed strong inhibition and even regression of tumor growth, and the tumors were almost disappeared on day 14 without body weight loss in non-small cell lung cancer (LXFL1121). In a pleuramesothelioma (PXF541) PDX model, UD-017 also showed regressive effect, and in gastric cancer (GXA3067) and sarcoma (SXFS117) PDX models, UD-017 completely inhibited the tumor growth. Conclusions: We propose UD-017 as a novel type of anticancer drug that shows complete antitumor responses in patient-derived xenograft models of diverse cancer types. c-Myc expression in cancer cells may be a biomarker for the antitumor effect of UD-017. These data support the rationale for further advancing towards clinical development. Citation Format: Takashi Matsushita, Sayaka Ogi, Kazuhiro Onuma, Hidetoshi Sunamoto, Ayumi Ogawa, Toru Hasegawa, Yasunori Tokunaga, Yasuhiro Aga, Shigeru Ushiyama. UD-017, a novel highly selective and orally active CDK7 inhibitor, shows a significant anticancer activity in patient-derived cancers [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 4835.
Breast-milk microbiome and risk of asthma by 6 years of age
Authors: I Hamynen, M. Taubel, A. M. Karvonen, L. Orivuori, O. Vaarala, E. Schmausser-Hechfellner, A. Hyvarinen, J. Riedler, C. Roduit, J. Dalphin, Erika von Mutius, S. Remes, J. Pekkanen, P. Kirjavainen
Journal: Allergy (2017)