tbuckley/cabot-search huggingface dataset:
Mast Cells Cause Apoptosis of Cardiomyocytes and Proliferation of Other Intramyocardial Cells In Vitro
Authors: MasatakeHara, AkiraMatsumori, KohOno, HiroshiKido, Myung-WooHwang, TadashiMiyamoto, AtsushiIwasaki, MasaharuOkada, KazukiNakatani, ShigetakeSasayama
Journal: Circulation (1999)

Background—Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure. However, their roles in pathogenesis of these diseases are unknown. Methods and Results—Cultured cardiomyocytes from neonatal rats were incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of ≈70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against rat mast cell chymase 1 (RMCP 1). RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes. In contrast, MCGs induced the proliferation of intramyocardial cells other than myocytes. RMCP ...
Abstract 2032: CXCR7 promotes the migration and invasion of head and neck squamous cell carcinoma through Smad2/Akt signaling
Authors: Nayoung Kim, Solbi Kim, Hyewon Ryu, Hyo Jin Lee
Journal: Cancer Research (2018)

Abstract Background: The chemokine receptor, CXCR7, has been shown to play an important role in the progression of several types of cancer. However, there have been few reports on the biological role of CXCR7 in head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the functional role of CXCR7 and the underlying molecular mechanism of disease progression in HNSCC. Methods: We characterized the expression of CXCR7 in tumor specimens from patients with HNSCC. The biological functions of CXCR7- and CXCR7-mediated signaling pathways were investigated in HNSCC cell lines with CXCR7 overexpression and treatment of SDF-1α, a major ligand of CXCR7, as well as knockdown of CXCR7. Results: CXCR7 was differentially expressed in human HNSCC patients. High expression of CXCR7 was associated with an aggressive tumor behavior. Overexpression of CXCR7 dramatically promoted cell migration and invasion in HNSCC cells, although it was not involved in cell proliferation and colony formation. CXCR7 knockdown using siRNA in HNSCC cells recovered the cell migratory and invasive behavior of HNSCC cells. CXCR7 overexpression also induced the epithelial-mesenchymal transition. Vimentin, Slug, and Twist were increased but E-cadherin and Ep-CAM were decreased by CXCR7 expression. Akt phosphorylation and Smad2 signaling activation were induced in HNSCC cells with CXCR7 overexpression. Treatment with a PI3K inhibitor reduced Slug and Twist levels while suppression of Smad2 signaling by siRNA reduced Akt phosphorylation, as well as Slug and Twist. Furthermore, inhibition of Smad2 decreased tumor cell migration and invasion in HNSCC. Conclusions: CXCR7 contributed to cell migration and invasion of HNSCC through the Smad2/Akt signaling axis, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC. Citation Format: Nayoung Kim, Solbi Kim, Hyewon Ryu, Hyo Jin Lee. CXCR7 promotes the migration and invasion of head and neck squamous cell carcinoma through Smad2/Akt signaling [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 2032.
Smoking, Surgery, and Venous Thromboembolism Risk in Women
Authors: SiânSweetland, LianneParkin, AngelaBalkwill, JaneGreen, GillianReeves, ValerieBeral
Journal: Circulation (2013)

Background—Evidence about the effect of smoking on venous thromboembolism risk, generally and in the postoperative period, is limited and inconsistent. We examined the incidence of venous thromboembolism in relation to smoking habits, both in the absence of surgery and in the first 12 postoperative weeks, in a large prospective study of women in the United Kingdom. Methods and Results—During 6 years’ follow-up of 1 162 718 women (mean age 56 years), 4630 were admitted to hospital for or died of venous thromboembolism. In the absence of surgery, current smokers had a significantly increased incidence of venous thromboembolism compared with never-smokers (adjusted relative risk 1.38, 95% confidence interval 1.28–1.48), with significantly greater risks in heavier than lighter smokers (relative risks 1.47 [95% confidence interval 1.34–1.62] and 1.29 [95% confidence interval 1.17–1.42] for ≥15 versus <15 cigarettes per day). Current smokers were also more likely to have surgery than never-smokers (relative ris...
A Role for p53 in the Adaptation to Glutamine Starvation through the Expression of SLC1A3
Authors: Mylène Tajan, Andreas K. Hock, Julianna Blagih, Neil A. Robertson, Christiaan F. Labuschagne, Flore Kruiswijk, Timothy J. Humpton, Peter D. Adams, Karen H. Vousden
Journal: Cell Metabolism (2018)

Highlights•p53 promotes cancer cell proliferation and survival under glutamine starvation•Aspartate metabolism supported by SLC1A3 is important under glutamine deprivation•SLC1A3 expression is induced by p53•Depletion of SLC1A3 impairs tumor growth in vivoSummaryNumerous mechanisms to support cells under conditions of transient nutrient starvation have been described. Several functions of the tumor-suppressor protein p53 can contribute to the adaptation of cells to metabolic stress and help cancer cell survival under nutrient-limiting conditions. We show here that p53 promotes the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine, and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation, and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition.Graphical abstract
Abstract 19924: National Cost Comparison of Trans Catheter Aortic Valve Replacement With Surgical Aortic Valve Replacement in Moderate to High Risk Patients With Severe Symptomatic Aortic Stenosis in New Zealand
Authors: SrijaBhattacharyya, MatthewRoskruge, SanjeevanPasupati, GerardDevlin, DavidSmyth, MarkWebster, PeterRuygrok
Journal: Circulation (2014)

Introduction: AS is a condition with an increasing prevalence in New Zealand (NZ). The natural history of severe AS is such that patients face a poor prognosis once the disease becomes clinically evident. Surgical aortic valve replacement (SAVR) is the standard of care, yet many are at high risk of poor outcomes due to comorbidity, frailty or anatomical limitations. Clinically TAVR may be an appropriate alternative treatment; however, at present it remains an expensive technology: the procurement cost of an Edwards Sapien trans catheter valve is NZD$30,000. Expansion of TAVR could have a major budget impact on the NZ public healthcare system. Conversely, the high cost of the transcatheter valve may be offset by intensive care unit stay and the cost of complications related to SAVR. Methods: To explore this further, we retrospectively compare index admission cost in AS patients with Euroscore 2 > 4 undergoing SAVR with those having TAVR. Patients were excluded if they had surgery outsourced to the private ...
Abstract 2132: Anti-vascular inflammatory nanoparticles inhibit tumor progression and metastasis through vascular normalization
Authors: Young Sun Choi, Soo Hyun Kang, Jong-Sup Bae, In-San Kim, You Mie Lee
Journal: Cancer Research (2018)

Abstract Vascular networks in cancer are structurally and functionally abnormal. Abnormal blood vessel development in cancer plays an important role in cancer growth and metastasis, and blocks delivery of chemotherapeutic drugs. Recent studies have revealed that the normalization of abnormal tumor vasculature is one of the promising approaches to treat cancer. Inflammatory microenvironment is one of the newly focused hallmarks of cancer, and tumor vasculature has similar features to that of inflammatory vessels. Thus, vascular inflammation is emerged as an attractive target for cancer treatment. We hypothesized that amelioration of vascular inflammation in tumor may induce vascular normalization leading to the inhibition of tumor progression and metastasis. Here, we investigated the function of ant-vascular nanoparticles in tumor growth and metastasis in LLC allograft tumor models and MMTV-PyMT, spontaneous breast tumor models using TFG and TFMG which are engineered a protein-cage nano-particle (ferritin) with both EPCR-targeting peptides (γ-carboxyglutamic acid (Gla) domain of protein C) and PAR-1-activating peptides (TRAP) of thrombin on its surface. As a result, tumor growth was significantly inhibited in the nanoparticle-injected group, and the lymph node metastasis was also decreased in both animal models. It has been found that the survival rate of the nanoparticle-injected group was prolonged. TFG and TFMG normalized abnormal tumor vasculature, that is, pericytes coverage in vasculatures was significantly increased but the hypoxic regions was decreased in the nanoparticle injected group. Furthermore, when the experiment was conducted by administering cisplatin and nanoparticles together in the LLC allograft tumor model, the tumor size was synergistically increased in the case of the nanoparticle and cisplatin combination administration compared to the cisplatin alone group. Taken together, anti-vascular inflammation nanoparticles with anti-vascular inflammatory properties normalized the abnormal blood vessels and inhibited tumor formation and metastasis. It is suggested that inducing normalization of cancer blood vessels by improving the inflammatory state of blood vessels may be a promising therapeutic method for effective cancer treatment. Citation Format: Young Sun Choi, Soo Hyun Kang, Jong-Sup Bae, In-San Kim, You Mie Lee. Anti-vascular inflammatory nanoparticles inhibit tumor progression and metastasis through vascular normalization [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 2132.
Excitation-Contraction Coupling of Isolated Cardiac Fibers with Disrupted or Closed Sarcolemmas: CALCIUM-DEPENDENT CYCLIC AND TONIC CONTRACTIONS
Authors: AlexandreFabiato, FrançoiseFabiato
Journal: Circulation Research (1972)

Single cells of adult rat ventricle were separated with 0.1% trypsin and 0.05-0.1% collagenase. Ten percent of these cells were tubular and striated, contracted spontaneously in the presence of 0.05 mM CaCl2 or after addition of 0.1-0.5 mM CaCl2, and developed contracture in 1 mM CaCl2. A resting potential of -30 to -50 mv and an action potential more than 100 msec in duration were recorded in some of the cells. These relatively intact cells were contrasted with myocardial fibers (10-100µ) obtained by homogenization. In the presence of 0.025 mM ethyleneglycol bis(β-aminoethylether)-N, N'-tetraacetic acid (EGTA), localized cyclic contractions with intracellular asynchrony were observed under the phase microscope in obviously disrupted areas of these mechanically separated fibers. These contractions were insensitive to the ratio of Na+ to K+, and neither resting potentials nor action potentials were observed. Thus, these disrupted fibers were considered skinned fibers of cardiac muscle; this assumption was ...
Abstract 2581: Plasma HPV cell free DNA as an earlier predictor of treatment response in advanced oropharyngeal cancer
Authors: Glenn J. Hanna, Julianna G. Supplee, Yanan Kuang, Kate Geary, Pasi A. Janne, Robert I. Haddad, Cloud P. Paweletz
Journal: Cancer Research (2018)

Abstract Purpose: Human papillomavirus (HPV) is associated with the majority of oropharyngeal squamous cell carcinomas (OPSCC), with a rising incidence of OPSCC predominantly among middle-aged men. Tumor-derived HPV cell-free (cf)DNA can be detected and quantified in circulation with high sensitivity and specificity. Although cfDNA has limited clinical application in monitoring locoregional spread of these tumors, up to 10% of HPV+ OPSCC patients present or recur with distant, metastatic disease. The potential of HPV DNA monitoring in this setting remains largely unexplored. Methods: We present a proof-of-concept prospective observational cohort of recurrent, metastatic (R/M) HPV+ OPSCC patients treated with standard systemic therapies. We utilized droplet digital (dd)PCR to identify and quantify HPV cfDNA (strains 16, 18, 31, 33 and 45) at multiple time points throughout treatment. We then compared HPV cfDNA concentration at various timepoints with clinical parameters such as disease burden and treatment response. Results: Clinicopathologic data from 12 R/M patients revealed a predominantly male cohort (11/12, 92%) with a median age of 55 at diagnosis. Eight (67%) were on immunotherapy treatments and the other four on standard chemotherapy during the study period (2.5 months). Plasma HPV cfDNA was detected in 6/12 (50%) samples (range 0-4460 copies/mL) in at least one timepoint during the study. All patients with undetectable HPV cfDNA had evidence of stable, low burden disease or no measurable lesions (near-complete response) on their current therapy. HPV cfDNA levels strongly correlated with both disease burden (p &amp;lt; 0.01) and distant disease sites (p &amp;lt; 0.01). In three cases, HPV DNA levels declined prior to contrast enhanced imaging findings which later confirmed treatment response (up to 14 days prior to planned imaging). Conclusion: Our results suggest that high sensitivity plasma HPV cfDNA levels can be an early indicator of treatment response. HPV cfDNA monitoring could significantly impact clinical decision-making and improve patient outcomes by informing treatment response or failure. Further studies are underway to validate these findings and determine how early cfDNA can detect metastatic disease. Citation Format: Glenn J. Hanna, Julianna G. Supplee, Yanan Kuang, Kate Geary, Pasi A. Janne, Robert I. Haddad, Cloud P. Paweletz. Plasma HPV cell free DNA as an earlier predictor of treatment response in advanced oropharyngeal 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 2581.
Abstract 4887: Mitochondrial SOD2 is the mainstay to protect the stemness-featured glioblastoma cells against drug-induced reactive oxygen stress
Authors: Kwang-Yu Chang, Chia-Hung Chien, Jui-Mei Chu, Pei-Hsuan Chung, Ming-Sheng Liu, Jian-Ying Chuang
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is a highly aggressive primary brain tumor with presence of stemness-featured cells that are prone to survive from cancer treatment. We reported Sp1-induced SOD2 was associated with the process to acquire temozolomide (TMZ) resistance that the significance remained to be elucidated. Resistant models were established through long-term coincubation with TMZ in GBM cell lines, which expressed significantly higher stemness properties in extreme limiting dilution analysis (ELDA) and serial transplantation. These cells also showed increased expression of SOD2. Enrichment of stemness-featured cells by spheroid culturing or by CD133-positive cells selection resulted in increased SOD2, suggesting their associations. The impact of the protein to glioma stem cells (GSCs) was then studied through SOD2 RNA interference (RNAi), displaying downregulated stemness features in the knockdown models. Functional studies of the resistant cells showed superior scavenging ability in TMZ- or H2O2-induced ROS that would be dysfunctioned in pretreatment with SOD2 RNAi. In addition, co-treatment with the reagents over the knockdown cells resulted in enhancement of apoptosis as well as inhibition in tumor spheroid culture and cell clonogenic formation, suggesting re-sensitization to the drug. By establishing in vivo model from patient derived xenograft implantation that was obtained from clinical resistant disease, the mouse receiving combination treatment with TMZ and SOD inhibitor had lower tumor proliferation comparing to those receiving TMZ alone. These data indicate that there was an association between SOD2 and the stemness features, suggesting the protein to play important roles in regulation of GSCs behavior. Down-regulation of SOD2 levels may thus be a potential therapeutic strategy for modulating stemness properties of GSCs, making these cells more susceptive to the chemo-therapeutic agent. Citation Format: Kwang-Yu Chang, Chia-Hung Chien, Jui-Mei Chu, Pei-Hsuan Chung, Ming-Sheng Liu, Jian-Ying Chuang. Mitochondrial SOD2 is the mainstay to protect the stemness-featured glioblastoma cells against drug-induced reactive oxygen stress [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 4887.
Analysis of Transcriptome Complexity Through RNA Sequencing in Normal and Failing Murine Hearts
Authors: Jae-HyungLee, ChenGao, GuangdunPeng, ChristopherGreer, ShuxunRen, YibinWang, XinshuXiao
Journal: Circulation Research (2011)

Rationale:Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac gene expression, current knowledge offers limited insights to the total complexity in cardiac transcriptome at individual exon level. Objective:To develop more robust bioinformatic approaches to analyze high-throughput RNA sequencing (RNA-Seq) data, with the focus on the investigation of transcriptome complexity at individual exon and transcript levels. Methods and Results:In addition to overall gene expression analysis, the methods developed in this study were used to analyze RNA-Seq data with respect to individual transcript isoforms, novel spliced exons, novel alternative terminal exons, novel transcript clusters (ie, novel genes), and long noncoding RNA genes. We applied these approaches to RNA-Seq data obtained from mouse hearts after pressure-overl...
Natural History of Very Severe Aortic Stenosis
Authors: RaphaelRosenhek, RobertZilberszac, MichaelSchemper, MartinCzerny, GeraldMundigler, SentaGraf, JuttaBergler-Klein, MichaelGrimm, HaraldGabriel, GeraldMaurer
Journal: Circulation (2010)

Background— We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. Methods and Results— We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67±16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) ≥5.0 m/s (average AV-Vel, 5.37±0.35 m/s; valve area, 0.63±0.12 cm2). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel ≥5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden dea...
Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer
Authors: Mercedes Herrera, Carlos Llorens, Marta Rodríguez, Alberto Herrera, Ricardo Ramos, Beatriz Gil, Antonio Candia, María Jesús Larriba, Pilar Garre, Julie Earl, Mercedes Rodríguez-Garrote, Trinidad Caldés, Félix Bonilla, Alfredo Carrato, Vanesa García-Barberán, Cristina Peña
Journal: Molecular Cancer (2018)

Exosome production from cancer-associated fibroblasts seems to be an important driver of tumor progression. We report the first in-depth biotype characterization of ncRNAs, analyzed by Next Generation Sequencing and Bioinformatics, expressed in established primary human normal and cancer-associated fibroblasts (CAFs) from cancer and normal mucosa tissues from 9 colorectal cancer patients, and/or packaged in their derived exosomes. Differential representation and enrichment analyses based on these ncRNAs revealed a significant number of differences between the ncRNA content of exosomes and the expression patterns of the normal and cancer-associated fibroblast cells. ncRNA regulatory elements are specifically packaged in CAF-derived exosomes, supporting a specific cross-talk between CAFs and colon cancer cells and/or other stromal cells, mediated by exosomes. These sncRNAs are potential biomarkers present in cancer-associated fibroblast-derived exosomes, which should thereby contribute to developing new non-invasive diagnostic, prognostic and predictive methods for clinical applications in management of cancer patients.
Left Main Coronary Artery to Left Atrial Fistula Causing Mild Pulmonary Hypertension
Authors: DimitrisTousoulis, StellaBrilli, KonstantinaAggelli, CostasTentolouris, ChristodoulosStefanadis, KostantinosToutouzas, AlexandraFrogoudaki, PavlosToutouzas
Journal: Circulation (2001)
The Hindsight Problem in Evaluating the Value of Ultrasonography in Cellulitis
Authors: Hyung J. Cho, Tuyet-Trinh N. Truong, Emma M. Loebel
Journal: JAMA Internal Medicine (2018)

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