tbuckley/cabot-search huggingface dataset:
Abstract P209: Gender Differences in Characteristics, Outcome at Discharge and 3-Month after Stroke in a National Acute Stroke Registry
Authors: Silvia Koton, David Tanne
Journal: Circulation (2013)

Introduction: Outcome of stroke has been reported poorer for women compared to men; however patients’ characteristics differ by gender, therefore adjusting for potential confounding effects is crucial for understanding the effect of gender on outcome after stroke. Hypothesis: We assessed the hypothesis that patients’ characteristics on admission, outcome at discharge and 3-months after stroke differ by gender. Methods: Data were derived from the triennial two-month national hospital-based Acute Stroke Israeli Registry (Feb-March 2004, March-April 2007, April-May 2010; the NASIS project). Unselected patients admitted to all hospitals (n=28) in Israel were included. Outcome at 3-month was assessed in a sub-sample of patients in the 2007 and 2010 periods. Logistic regression models were used in the study of gender as an independent risk factor for death and poor functional outcome. Results: In total, 5034 patients [ischemic stroke 4,452 (88.5%), ICH-485 (9.6%), undetermined stroke-97 (1.9%)] were included, of them 2285 (45.4%) women. Women were significantly older [mean (SD) 73.3 (13.1) years] than men [68.7 (12.9)] (p&lt;0.0001). The proportion of hypertension, atrial fibrillation, prior heart disease, peripheral artery disease and prior disability (mRS≥2) was higher in women, and they presented with more severe stroke than men. Rates of in-hospital death and poor functional outcome were higher for women compared with men. Following adjustment for age, NIHSS, risk factors and prior disability, risk estimates (ORs, 95%CI) were 0.7 (0.6-1.0) for in-hospital death, 1.4 (1.0-1.9) for discharge to a nursing home, and 1.0 (0.9-1.2) for disability. Follow-up at 3-month was completed for 1040 patients, 436 (41.9%) women. Rates of 3-month mortality, Barthel Index≤60, dependency by 2-simple questions and living in a nursing home were significantly higher for women compared with men. However, adjusted risk estimates were not higher: OR 1.0 (95%CI 0.5-1.8) for death at 3-months, 1.4 (1.0-2.0) for Barthel Index≤60, 1.2 (0.9-1.7) for dependency and 0.9 (0.6-1.4) for living in a nursing home. Conclusion: In conclusion, women are at increased risk of death and poor functional outcome after stroke mainly due to differences in age, risk factors, functional status prior to stroke and stroke severity compared with men.
Abstract 102: RUNX3 inhibits invasiveness and stemness through downregulation of Gli-1 in colon cancer cells
Authors: Bo Ram Kim, Yoo Jin Na, Jung Lim Kim, Soyeon Jeong, Seong Hae Park, Min Jee Jo, YoonA Jeong, Dae-Hee Lee, Sang Cheul Oh
Journal: Cancer Research (2018)

Abstract Disabled tumor suppressor genes and hyperactive oncogenes contribute considerably to cell fates during cancer development via genetic alterations such as somatic mutations. To date, little is known about how tumor suppressor genes react to diverse oncogenes during tumor progress. Our previous report showed that RUNX3 inhibits metastasis by preventing vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in colorectal cancer. Hedgehog signaling is crucial for the physiological maintenance and self-renewal of stem cells, and its deregulation is responsible for their tumor development. The mechanisms that inhibit this pathway during the proliferation are poorly understood. Here, we show that the tumor suppressor RUNX3 modulates tumorigenesis in response to cancer cells induced by inhibition by oncogene Gli-1 ubiquitination. Moreover, we demonstrated that RUNX3 and Gli-1 expression had inverse correlation in colorectal cancer cells and tissues. We observed a direct interaction between RUNX3 and Gli-1, promoting ubiquitination of Gli-1 at the intracellular level. The increased ubiquitination of Gli-1 was induced through the E3 ligase β-TrCP. This novel RUNX3-dependent regulatory loop may limit the extent and duration of Hedgehog signaling during extension of tumor initiation capacity. Base on this research, a search for agents that can induce RUNX3 might result in new and effective therapies for colorectal cancer. Citation Format: Bo Ram Kim, Yoo Jin Na, Jung Lim Kim, Soyeon Jeong, Seong Hae Park, Min Jee Jo, YoonA Jeong, Dae-Hee Lee, Sang Cheul Oh. RUNX3 inhibits invasiveness and stemness through downregulation of Gli-1 in colon cancer 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 102.
Peroxisome Proliferator-Activated Receptor Activators Inhibit Thrombin-Induced Endothelin-1 Production in Human Vascular Endothelial Cells by Inhibiting the Activator Protein-1 Signaling Pathway
Authors: PhilippeDelerive, FrançoiseMartin-Nizard, GiuliaChinetti, FrançoisTrottein, Jean-CharlesFruchart, JamilaNajib, PatrickDuriez, BartStaels
Journal: Circulation Research (1999)

Abstract—Endothelin-1 (ET-1), a 21-amino acid vasoactive peptide mainly produced by vascular endothelial cells, is involved in the regulation of vascular tone and smooth muscle cell proliferation. Peroxisome proliferator-activated receptors (PPARs), key players in lipid and glucose metabolism, have been implicated in metabolic disorders that are predisposing to atherosclerosis. Because of the potential role of ET-1 in vascular disorders such as hypertension and atherosclerosis, we investigated the regulation of ET-1 expression by PPAR activators. Western blot and reverse transcription–polymerase chain reaction analyses demonstrated that both PPARα and PPARγ are expressed in human coronary artery endothelial cells as well as in endothelial cell lines such as HMEC-1 and ECV304. In bovine aortic endothelial cells and HMEC-1 cells, both PPARα and PPARγ ligands inhibited thrombin-induced ET-1 secretion, whereas basal ET-1 secretion was only slightly suppressed. Reverse transcription–polymerase chain reaction e...
Abstract 12088: Low Computed Tomography Attenuation Value of Epicardial Fat is a Useful Marker for Coronary Stenosis
Authors: Aiko Sakamoto, Masae Uehara, Nobukazu Ishizaka, Jiro Ando, Ryozo Nagai, Issei Komuro
Journal: Circulation (2015)

Background: Epicardial fat volume (EFV) is recognized as an independent risk factor for coronary atherosclerosis. However, it remains unclear whether the computed tomography (CT) attenuation value of epicardial fat is associated with coronary stenosis. Methods: We analyzed the association of epicardial fat CT attenuation value (EFCTA) and EFV with obstructive coronary artery disease (CAD) in 355 patients (203 men; mean age, 68 ± 11 years) who underwent coronary CT angiography. EFCTA was calculated as the mean CT values of 5 regions of interest in epicardial fat. Results: A total of 200 (56.3%) patients were judged to have obstructive CAD. There was a strong correlation between EFCTA and EFV (R=-0.618, P&lt;0.001). EFCTA and EFV were significantly lower and higher, respectively, in patients with obstructive CAD (EFCTA, -93.0 HU [interquartile range, IR -101.0 - -84.6]; EFV, 110 mL [IR 83 - 146]) than in those without (EFCTA, -88.8 HU [IR -95.6 - -79.4], P&lt;0.001; EFV, 89 mL [IR 68 - 122], P&lt;0.001). In logistic regression analysis using age and gender as covariates, the lowest EFCTA quartile (&lt;-98.8 HU) was significantly associated with obstructive CAD (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.68 - 6.34, P&lt;0.001). Age- and gender-adjusted logistic regression analysis showed that the highest EFV quartile (≥138 mL) had a significant association with obstructive CAD (OR 2.59, 95% CI 1.35 - 4.96, P=0.004). When age, gender, body mass index, smoking, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, and quartiles of EFCTA and EFV were used as independent valuables, the association of the lowest EFCTA quartile, but not the highest EFV quartile, with obstructive CAD remained statistically significant (OR 2.48, 95% CI 1.05 - 5.85, P=0.038). Conclusions: Low EFCTA was significantly associated with obstructive CAD, independent of traditional cardiovascular risk factors, suggesting that EFCTA may be a novel marker for assessment of CAD.
Acceptability, Accuracy, and Safety of Disposable Transnasal Capsule Endoscopy for Barrett's Esophagus Screening
Authors: Sarmed S. Sami, Prasad G. Iyer, Prachi Pophali, Magnus Halland, Massimiliano di Pietro, Jacobo Ortiz-Fernandez-Sordo, Jonathan R. White, Michele Johnson, Indra Neil Guha, Rebecca C. Fitzgerald, Krish Ragunath
Journal: Clinical Gastroenterology and Hepatology (2018)

Background & AimsScreening for Barrett's esophagus (BE) with conventional esophagogastroduodenoscopy (C-EGD) is expensive. We assessed the performance of a clinic-based, single use transnasal capsule endoscope (EG Scan II) for the detection of BE, compared to C-EGD as the reference standard.MethodsWe performed a prospective multicenter cohort study of patients with and without BE recruited from 3 referral centers (1 in the United States and 2 in the United Kingdom). Of 200 consenting participants, 178 (89%) completed both procedures (11% failed EG Scan due to the inability to intubate the nasopharynx). The mean age of participants was 57.9 years and 67% were male. The prevalence of BE was 53%. All subjects underwent the 2 procedures on the same day, performed by blinded endoscopists. Patients completed preference and validated tolerability (10-point visual analogue scale [VAS]) questionnaires within 14 days of the procedures.ResultsA higher proportion of patients preferred the EG Scan (54.2%) vs the C-EGD (16.7%) (P < .001) and the EG Scan had a higher VAS score (7.2) vs the C-EGD (6.4) (P = .0004). No serious adverse events occurred. The EG Scan identified any length BE with a sensitivity value of 0.90 (95% CI, 0.83–0.96) and a specificity value of 0.91 (95% CI, 0.82–0.96). The EG Scan identified long segment BE with a sensitivity value of 0.95 and short segment BE with a sensitivity values of 0.87.ConclusionsIn a prospective study, we found the EG Scan to be safe and to detect BE with higher than 90% sensitivity and specificity. A higher proportion of patients preferred the EG Scan to C-EGD. This device might be used as a clinic-based tool to screen populations at risk for BE. ISRCTN registry identifier: 70595405; ClinicalTrials.gov no: NCT02066233.
Abstract 283: SGK1-Dependent Sirt3 Phosphorylation Regulates Mitochondrial Dynamics
Authors: Dallas Ellis, Takara Scott, Wei Zhong, Oguljahan Babayeva, Sharon C Francis
Journal: Circulation Research (2016)

Mitochondrial dynamics (i.e. fusion and fission) is impaired in models of obesity and can result in target organ dysfunction. However, the mechanisms that regulate mitochondrial dynamics in the setting of obesity are not completely understood. The objectives of this study are to examine a role for and determine the molecular mechanisms of serum and glucocorticoid-inducible kinase 1 (SGK1) in obesity-related mitochondrial dynamics in the vasculature. We recently reported that aortic expression of SGK1 is elevated in a model of diet-induced obesity (DIO) in vivo and by resistin; a fat-derived adipokine, in human aortic smooth muscle cells (SMC) in vitro . To directly examine the effects of SMC-derived SGK1 on mitochondrial dynamics, wildtype and SMC-specific SGK1 knockout mice were subjected to DIO for eight weeks. Our results indicate that SMC-specific deletion of SGK1 induced a fused, elongated mitochondrial phenotype in aortic SMC in vivo and attenuated obesity-mediated arterial mitochondrial fragmentation suggesting a role for SGK1 in stimulation of mitochondrial fission. To determine the molecular mechanism for this effect, we performed a proteomic screen for novel SGK1 substrates and identified the mitochondrial deacetylase SIRT3 as a novel SGK1 target. Mass spectrometry indicates SGK1 phosphorylates SIRT3 on serine103. Increasing doses of resistin augmented SIRT3-S103 phosphorylation and caused a concomitant decrease in total SIRT3 in rat aortic SMC in vitro . To examine whether SGK1-dependent SIRT3 phosphorylation regulates the mitochondrial fission protein machinery; we evaluated total and activated levels of Drp1, the mitochondrial fission regulator, in response to ectopic expression of SIRT3 wildtype, phospho-memetic (S103D) and phospho-deficient (S103A) mutants. SIRT3-S103D increased total Drp1 and activated Drp1 protein levels an effect inhibited by SIRT3-S103A. These findings implicate elevated resistin observed during obesity in stimulation of SGK1 and subsequent phosphorylation of SIRT3 leading to activation of Drp1 and stimulation of arterial mitochondrial fragmentation.
Abstract 2805: Combretastatins as highly cytotoxic natural compounds
Authors: Petr Dzubak, Jiři Rehulka, Sona Gurska, Uwe Riener, Marian Hajduch
Journal: Cancer Research (2018)

Abstract Combretastatins originally isolated from the South African willow tree Combretum cafrum are highly cytotoxic natural products, but their use is limited because of the cis/trans isomerization of the cis-stilbene moiety under physiological conditions. Herein we report the preparation of cis-restrained carbocyclic analogs of CA-4. The compounds, which differ by the size and hybridization of the carbocyclic ring have been evaluated for cytotoxic activity in vitro against a panel of human cancer and two non-tumor fibroblast cell lines and for their ability to inhibit tubulin polymerization. Biological data, supported by molecular docking studies, identified a cyclobutenyl derivative of the natural product as a promising drug candidate with selective nanomolar cytotoxic activity towards cancer cell lines, showing high potency against multidrug-resistant cells and inhibiting tubulin polymerization. This work was supported by Ministry of Health of the Czech Republic (15-31984A), internal grant of Palacky University (IGA_LF_2017_026) and by the Czech Ministry of Education, Youth and Sports LO1304, CZ-OPENSCREEN, (LM2015063) and EATRIS (LM2015064). Citation Format: Petr Dzubak, Jiři Rehulka, Sona Gurska, Uwe Riener, Marian Hajduch. Combretastatins as highly cytotoxic natural compounds [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 2805.
Expression of Costimulatory Molecules B7–1, B7–2, and CD40 in the Heart of Patients With Acute Myocarditis and Dilated Cardiomyopathy
Authors: YoshinoriSeko, NaoyukiTakahashi, ShigeruIshiyama, ToshiroNishikawa, TakeshiKasajima, MichiakiHiroe, ShinSuzuki, SugaoIshiwata, SachioKawai, MiyukiAzuma, HideoYagita, KoOkumura, YoshioYazaki
Journal: Circulation (1998)

Background—In patients with acute myocarditis and dilated cardiomyopathy (DCM), we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen-presenting cells (APCs) as well as the main signal provided by binding of T-cell receptors to the antigen. Methods and Results—To investigate the roles of the costimulatory molecules B7–1, B7–2, and CD40 in the development of acute myocarditis and DCM, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, because both killer lymphocytes are thought to damage B7–1–expressing APCs. We found that B7–1, B7–2, and CD40 were moder...
Abstract 500: A p53/miR-30a/ZEB2 axis controls basal-like/triple-negative breast cancer aggressiveness
Authors: Valentina Damiano, Alessandra di Gennaro, Giulia Brisotto, Michela Armellin, Tiziana Perin, Antonella Zucchetto, Michela Guardascione, Herman P. Spaink, Claudio Doglioni, Ewa Snaar-Jagalska, Manuela Santarosa, Roberta Maestro
Journal: Cancer Research (2018)

Abstract Inactivation of p53 plays a major role in the poor prognosis of basal-like /triple-negative breast cancers (TNBC). However, how p53 inactivation impinges upon TNBC aggressive phenotype is only partially defined. Here we report the identification of a novel axis involving p53, miR30a and ZEB2. We provide evidence that p53 affects the expression of ZEB2, a transcription factor involved in epithelial-mesenchymal transition (EMT), by relying on miR-30a. In particular, we found that p53 regulates miR-30a expression by direct promoter binding and that miR30a targets ZEB2. Finally, we provide evidence that the new p53/miR-30a/ZEB2 axis controls tumor cell invasion and migration and that reduced miR-30a expression correlates with p53 inactivation and dismal prognosis in human breast cancers. Overall, this study highlights the existence of a novel axis linking p53 to EMT via miR-30a, and adds a novel element to the complex network whereby p53 inactivation impinge upon tumor aggressiveness. Citation Format: Valentina Damiano, Alessandra di Gennaro, Giulia Brisotto, Michela Armellin, Tiziana Perin, Antonella Zucchetto, Michela Guardascione, Herman P. Spaink, Claudio Doglioni, Ewa Snaar-Jagalska, Manuela Santarosa, Roberta Maestro. A p53/miR-30a/ZEB2 axis controls basal-like/triple-negative breast cancer aggressiveness [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 500.
Abstract 12186: Correlations Between Sleep Disordered Breathing Indexes and Cardiac Functional Parameters in Patients With Chronic Heart Failure
Authors: TadamitsuNakashima, TomokoOhkusa, TomokoNao, NorikoHarada, YasuakiWada, TakeshiUeyama, ShigekiKobayashi, YasuhiroIkeda, HiroyukiSawatari, AkikoChishaki, Shin-ichiAndo, MasafumiYano
Journal: Circulation (2014)

Background and Purpose: High prevalence of sleep disordered breathing (SDB) in patients with chronic heart failure (CHF) was reported. In general, apnea hypopnea index (AHI) is used as a severity of SDB index. On the other hand, it was reported there was not good correlation between AHI and prognosis in CHF patients with SDB. The purpose of this study was to investigate the correlations between cardiac functional characteristics and indexes of SDB severity [AHI, 3% oxygen desaturation index (ODI), and averaged time desaturation summation index (TDSI)] in CHF patients. Methods: One hundred thirty-six consecutive CHF patients, who were hospitalized from June 2012 to March 2014, were screened at their stable phase. Sleep studies were performed by in-hospital overnight full polysomnograpy (PSG). The following equation was used to determine TDSI. TDSI=total sleep time x (100-mean oxygen saturation). Results: The mean age was 68±14 years, and 81 men. Underlying etiology was ischemic cardiomyopathy (ICM) in 33 p...
Decline in physical functioning in first 2 years after breast cancer diagnosis to predict survival in older women.
Authors: Mary Elizabeth Sehl, Xiang Lu, Rebecca A Silliman, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2012)

e11003 Background: Breast cancer patients often experience a decline in physical functioning following cancer diagnosis. Although most patients recover after treatment, some patients do not. These changes may be magnified in older women with comorbid conditions and could impact survival outcomes. Methods: We used longitudinal data from a prospective cohort study of women 65+ years of age, recruited shortly after diagnosis of early stage breast cancer, to examine changes in self-reported physical functioning measured with the Physical Function Index (PF-10) of the Medical Outcomes Study Short Form-36 (SF-36). Outcomes were constructed for small (0.2 SD), medium (0.5 SD), and large (0.8 SD) decline in the PF-10 measurement over two intervals 1) 3 to 15 months following cancer diagnosis, encompassing treatment and early recovery, and 2) 3 to 27 months following cancer diagnosis, in order to detect sustained recovery versus persistent decline. Cox-proportional hazards regression was used to examine association between survival and decline in PF-10 scores. Results: A large (&gt; 0.8 SD) decline in PF-10 scores from 3 to 27 months predicted shorter 10 year survival (HR=1.37, 95% CI 1.07-1.74). Persistent decline at 27 months was associated with less education, higher baseline PF-10, increased comorbidity, and lack of exercise at baseline. Conclusions: Older women with breast cancer who experience a large and persistent decline in PF-10 are at increased mortality risk. Future research should examine the value of clinical assessment of physical function as a marker for mortality and test interventions to prevent decline in physical function to improve post-treatment survival outcomes.
Abstract 1182: Exploring longitudinal intra-tumor heterogeneity in cancer using whole genome sequencing and RNA rescue
Authors: Rahul Parulkar, Steve Benz, Charlie Vaske, Amie Radenbaugh, Christopher Szeto
Journal: Cancer Research (2018)

Abstract We present a methodology for confidently characterizing subclonal exonic variants by pairing whole genome sequencing (WGS) with transcriptomics (RNAseq). We demonstrate the utility of this method by studying subclonal population changes in longitudinally collected samples. Detection of variants specific to minority subclones has ordinarily only been achievable with very high-depth sequencing obtained by whole exome (WES) or targeted sequencing, and most available tools for studying subclonality require WES data as input. Although WGS provides more coverage breadth than WES, identifying subclonal mutations by WGS alone is difficult due to reduced read support for each variant. Detecting minority variants in WGS data is made especially difficult when tumor purity is low and subclonality is high. RNAseq is typically performed at high-depth and may be useful for replacing WES in detecting subclonal variants. Our method has two steps: 1) Use WGS to establish a low-confidence preliminary set of variants present in the tumor, and 2) bolster the confidence in those variants by observing whether the variants are expressed in the RNAseq. We used this methodology to generate WES-like data from WGS+RNAseq in simulated data, and show that we can correctly identify subclonal populations using publicly available tools designed for WES data. Additionally, we demonstrate using this method to characterize the evolutionary lineage of the tumor population in a patient who was biopsied multiple times throughout several treatments, for whom only WGS and RNAseq data is available. Our proposed method resulted in 60% more confident variants than its WGS-only counterpart. As tumor tissue availability is low and cost of sequencing is substantial, the choice of which molecular characterizations to perform is difficult. Here we show that paired WGS and RNAseq can be leveraged to infer information typically only obtained from WES, in addition to providing intergenic and expression information. Citation Format: Rahul Parulkar, Steve Benz, Charlie Vaske, Amie Radenbaugh, Christopher Szeto. Exploring longitudinal intra-tumor heterogeneity in cancer using whole genome sequencing and RNA rescue [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 1182.