tbuckley/cabot-search huggingface dataset:
Abstract 450: Brg1 Attenuates Cardiac Dysfunction by Activating Sonic Hedgehog Pathway in Acute Myocardial Infarction
Authors: Ning Hou, Sujuan Li, Guanfeng Liang, Xiaoxia Qiu, Jiandong Luo
Journal: Circulation Research (2017)

Background: Brahma-related gene 1 (Brg1), the core ATPase subunit of a large chromatin remodeling complex, plays critical role in the regulation of gene expression during cardiac growth, differentiation. In adults, Brg1 is turned off in cardiomyocytes and reactivated by cardiac stress. How Brg1 in myocardial infarction (MI) is poorly understood. The sonic hedgehog (Shh) pathway was activated to protect the injured cardiomyocytes during the development of MI. However, by which Shh activation is mediated in MI still remains to be determined. Methods and results: Adult male C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery for MI model. We investigated Brg1 activation and how it regulated the gene expressions of Shh pathway in peri-infarct zone in MI mice. Our data demonstrated that in peri-infarct zone, the protein of Brg1 was significantly increased 7 days after MI compared with the sham group in control mice, accompanied by upregulation of shh, patched-1 (Ptch1), and glioma-associated oncogene-1(Gli1). We further revealed that with adenoviral intramyocardial injection, the Brg1 overexpression reduced the percentage myocardial infarct, improved cardiac dysfunction, decreased the number of apoptotic cells and upregulated the ratio of Bcl-2/Bax in MI mice. Conversely, shRNA-mediated knockdown of Brg1 enlarged the percentage myocardial infarct, exacerbated cardiac dysfunction, increased the apoptotic cells and downregulated the ratio of Bcl-2/Bax. More importantly, the Brg1 overexpression increased Shh, Ptch1 and Gli1 expressions, whereas Brg1 knockdown suppressed Shh, Ptch1 and Gli1 expressions. Chromatin immunoprecipitation confirmed that Brg1 were recruited to the regulatory elements of Shh, Ptch1 and Gli1. This recruitment was associated with transcriptional upregulation of these three genes. Conclusions: This study indicated that in MI mice, the myocardial Brg1 is upregulated and that the upregulated Brg1 contributes to protection of cardiac function and activation of Shh pathway. Strategies that are aimed at augment the Brg1-Shh pathway may offer useful means for preventing and treating cardiac dysfunction in patients with MI. Key words: Acute myocardial infarction, Brg1, Shh pathway
Natriuretic Peptides Predict Symptom-Free Survival and Postoperative Outcome in Severe Aortic Stenosis
Authors: JuttaBergler-Klein, UrsulaKlaar, MariaHeger, RaphaelRosenhek, GeraldMundigler, HaraldGabriel, ThomasBinder, RichardPacher, GeraldMaurer, HelmutBaumgartner
Journal: Circulation (2004)

Background— The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown. Methods and Results— B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70±12 years; mean gradient, 64±21 mm Hg; valve area, 0.64±0.15 cm2) who were followed up for 377±150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus ≥80 pmol/L was 100%, 88±7%, 88±7%, and 69±13% compared with 92±8%, 58±14%, 35±15%, and 18±15%, respectively (P<0.001). ...
Abstract 16: A wide-spectrum analysis of angiogenesis-related factors in ovarian cancer reveals a signature potentially for prognosis and therapeutic targeting
Authors: Chih-Lin Kuo
Journal: Cancer Research (2018)

Abstract Ovarian cancer is the first leading cause of death from woman gynecological malignancies worldwide. It is typically diagnosed at a late stage with a poor 5-year survival rate less than 30%. In the progress of ovarian cancer, angiogenesis-related factors not only induce neovascularization for supporting tumor growth but also accelerate ascites production, which helps the peritoneal metastasis and is associated with poor disease prognosis. Therefore, angiogenesis-related factors are thought to be particularly crucial in the persistence of ovarian cancer and have become key targets in clinical research. Although the expression of some angiogenesis-related factors in ovarian cancer has been sporadically reported, analysis of the profile of angiogenesis-related factors in a whole spectrum manner is needed to evaluate their cruciality and relationship. In our study, totally 104 angiogenesis-related factors were used to analyze their transcriptional changes along with ovarian cancer progression in the data of 601 patients obtained from TCGA datasets (AgilentG4502A_07_2 and AgilentG4502A_07_3). 33 candidates with significantly differential expression (p &amp;lt; 0.05) between normal and any stage were initially revealed. To narrow down the candidates, these factors were ranked by the significance of expressional changes between normal and all various stages and 13 factors with the most significant difference (p &amp;lt; 0.0001) were selected and their fold changes were further shown in a heat-map manner; these included MMP9, VEGFA, CXCL10, TIMP2, AGRP, MMP8, IGFBP-1, ENG, TEK, FGF7, CSF3, ANGPTL5, ANGPTL7. Moreover, Ingenuity Pathway Analysis (IPA) and DAVID database analysis were applied to analyze their functional categories in angiogenesis. In conclusion, we developed a signature of angiogenesis-related factors for patients with ovarian cancer. With appropriate validation, it can be applied as a prognostic index or used to select certain candidates for developing targeted therapies. Citation Format: Chih-Lin Kuo. A wide-spectrum analysis of angiogenesis-related factors in ovarian cancer reveals a signature potentially for prognosis and therapeutic targeting [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 16.
Omega-3 Polyunsaturated Fatty Acids Prevent Atrial Fibrillation Associated With Heart Failure but Not Atrial Tachycardia Remodeling
Authors: MasaoSakabe, AkikoShiroshita-Takeshita, AngeMaguy, ChloeDumesnil, AnilNigam, Tack-KiLeung, StanleyNattel
Journal: Circulation (2007)

Background— There is epidemiological evidence that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF), but clinical data are conflicting. The present study assessed the effects of PUFA on AF in experimental models. Methods and Results— We studied the effects of oral PUFA supplements in 2 experimental AF paradigms: electrical remodeling induced by atrial tachypacing (400 bpm for 1 week) and congestive heart failure–associated structural remodeling induced by ventricular tachypacing (240 bpm for 2 weeks). PUFA pretreatment did not directly change atrial effective refractory period (128±6 [mean±SEM] versus 127±2 ms; all effective refractory periods at 300-ms cycle lengths) or burst pacing–induced AF duration (5±4 versus 34±18 seconds). Atrial tachypacing dogs had shorter refractory periods (73±6 ms) and greater AF duration (1185±300 seconds) than shams (119±5 ms and 20±11 seconds; P<0.01 for each). PUFAs did not significantly alter atrial tachypacing effects on refractory...
Dietary Measures to Prevent Sudden Unexpected Death in Epilepsy—Reply
Authors: Orrin Devinsky, Philippe Ryvlin, Daniel Friedman
Journal: JAMA Neurology (2018)

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Abstract 18474: Iron Deficiency Independently and Strongly Predicts Risk of Cardiovascular Death and Myocardial Infarction in Patients With Acute Coronary Syndrome
Authors: Mahir Karakas, Christoph Waldeyer, Francisco Ojeda, Renate Schnabel, Karl Lackner, Stefan Anker, Dirk Westermann, Stefan Blankenberg, Tanja Zeller
Journal: Circulation (2016)

Objective: The clinical relevance of iron deficiency (ID) in acute coronary syndrome (ACS) remains unclear. We aimed to evaluate the prognostic value of ID in ACS. Methods: In the prospective AtheroGene study (n=836), levels of ferritin, iron and transferrin were measured. ID was defined as ferritin below 100 μg/L, or as ferritin between 100-299 μg/L, if the transferrin saturation was below 20%. The main outcomes were nonfatal myocardial infarction (MI) and cardiovascular (CV) death. Results: 29.3 % of the subjects were categorized as iron deficient. ID prevalence was higher in women (41.0 %), and in patients with anaemia (45.7 %). During a median follow-up of 4.0 years, 13.3 % suffered an endpoint. ID strongly predicted MI and CV death in multivariate Cox regression adjusted for sex, age, BMI, smoking, hypertension, diabetes, and dyslipidemia (HR 1.52 [95 % CI 1.03 - 2.26; p=0.037]) and remained significant (HR 1.73 [95 % CI 1.07 - 2.81; p=0.026]) after additional adjustment for NT-proBNP, troponin and h...
Fluid Shear Stress Transcriptionally Induces Lectin-like Oxidized LDL Receptor-1 in Vascular Endothelial Cells
Authors: TakatoshiMurase, NoriakiKume, RisaKorenaga, JojiAndo, TatsuyaSawamura, TomohMasaki, ToruKita
Journal: Circulation Research (1998)

Abstract—Fluid shear stress has been shown to modulate various endothelial functions, including gene expression. In this study, we examined the effect of fluid shear stress on the expression of lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for atherogenic oxidized LDL in cultured bovine aortic endothelial cells (BAECs). Exposure of BAECs to the physiological range of shear stress (1 to 15 dyne/cm2) upregulated LOX-1 protein and mRNA in a time-dependent fashion. LOX-1 mRNA levels peaked at 4 hours, and LOX-1 protein levels peaked at 8 hours. Inhibition of de novo RNA synthesis by actinomycin D totally abolished shear stress–induced LOX-1 mRNA expression. Furthermore, nuclear runoff assay showed that shear stress directly stimulates transcription of the LOX-1 gene. Chelation of intracellular Ca2+ with quin 2-AM completely reduced shear stress–induced LOX-1 mRNA expression; furthermore, the treatment of BAECs with ionomycin upregulated LOX-1 mRNA levels in a dose-dependent manner. Taken toget...
Abstract 10945: Impact of Natural or Postoperative Survival Patterns in Long-term Outcome of Adult Survivors With Congenital Heart Disease
Authors: Pastora Gallego, Jose M Oliver, Ana E Gonzalez Garcia, Diego Garcia Hamilton, Raquel Yotti Alvarez, Ignacio Ferreira Gonzalez, Francisco Fernandez Aviles
Journal: Circulation (2015)

Background: Life expectancy of adult survivors with congenital heart disease (CHD) is related to CHD complexity but impact of natural or postoperative survival patterns on long-term outcome have not been reported. Methods: In a prospective cohort of 3,334 adults (50.6% males) with CHD, followed up to 24 years in a single tertiary centre, we analyzed all-cause mortality, annual death rate, median age of survival (MAS) and standardized mortality ratio (SMR). Data provided by the Spanish national death index were used for mortality analysis. Lesions were classified into 3 groups according to CHD complexity: simple (1,647); moderate (1,283); and severe (404). Patients were then classified into 4 subgroups according to survival pattern: repaired in childhood (1,377); repaired in adulthood (759); CHD that did not require operation (1,035); and inoperable CHD (163). Results: Median age at first examination was 22 years (IQ range 18-39) and median follow-up time 10.6 years (1-18). At the end of the study 336 patients had died (prevalence 10%; annual death rate 0.89%). In inoperable patients the estimated MAS was significantly lower (48.9 yrs; 95% CI 44-53), but there were not significant differences in MAS between patients repaired in childhood (75.9 yrs), repaired in adulthood (76.0 yrs) or that did not require repair (77.5 yrs). SMR in this latter group was 1.70 (95% CI 1.3-2.1)] but patients repaired in adulthood, repaired in childhood or inoperable had an increased SMR of 2.06 (95% CI 1.7-2.5), 5.87 (95% CI 4.5-7.7) and 24.1 (95% CI 18-33) respectively. The table shows a classification of long-term outcome depending on CHD complexity and survival pattern. Conclusion: Adult survivors that do not require intervention and patients with repaired simple CHD have excellent life-long prognostic indexes. Excess mortality was demonstrated in repaired moderately complex CHD . Patients with CHD of great complexity have the worst prognosis, especially those that are inoperable.
Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography
Authors: Mélanie Deschasaux, Kristien E. Bouter, Andrei Prodan, Evgeni Levin, Albert K. Groen, Hilde Herrema, Valentina Tremaroli, Guido J. Bakker, Ilias Attaye, Sara-Joan Pinto-Sietsma, Daniel H. van Raalte, Marieke B. Snijder, Mary Nicolaou, Ron Peters, Aeilko H. Zwinderman, Fredrik Bäckhed, Max Nieuwdorp
Journal: Nature Medicine (2018)
Abstract 3835: Targeting loss of MTAP expression in glioblastoma multiforme with a combination of 2-fluoroadenine and methylthioadenosine
Authors: Baiqing Tang
Journal: Cancer Research (2018)

Abstract Methylthioadenosine Phosphorylase (MTAP) is a key enzyme in the purine and methionine salvage pathways that convert the polyamine byproduct 5′-deoxy-5′-methylthioadenosine (MTA) into adenine and methylthioribose-1-phosphate. Homozygous deletion of the MTAP gene is observed in 55% of all glioblastoma multiforme (GBM) tumors. Since MTAP is a house-keeping enzyme found in all normal tissues, the lack of MTAP in GBM makes MTAP-loss a potential therapeutic target. In this study, we explore a novel strategy to target MTAP-loss in GBM by combining 2-fluoroadenine (2FA), a highly toxic adenine analogue, with MTA. Because MTAP is expressed in all normal tissues, MTA will be converted to adenine, which will protect against 2FA toxicity. However, in tumor cells, the effects of 2FA will not be ameliorated because they lack MTAP. Here we show that there is undetectable expression of MTAP in A172 and U87 GBM cell lines by both western blot and MTAP enzyme activity assays. In vitro toxicity studies in which cells were cultured with either 2FA alone or 2FA plus MTA revealed that both cell lines were sensitive to 2FA with or without MTA. The LD50 of A172 cells was 110 nM (2FA) and 127 nM (2FA + 5 μM MTA), while for U87 cells it was 397 nM (2FA) and 323 nM (2FA + 5 μM MTA). This is in sharp contrast to MTAP+ NIH3T3 cells in which we observed a 44 fold shift in the ratio of the LD50 concentration in the presence and absence of MTA (160 nM versus 7000 nM). Addition of MTA protected normal tissues against 2FA toxicity in SCID mice. SCID mice subcutaneously injected with either A172 or U87 cells and then treated with 2FA(10 mg/kg) + MTA(50 mg/kg) showed significantly reduced tumor growth compared to vehicle treated controls. Our results indicated that 2FA+MTA might be effective in treating GBM. Citation Format: Baiqing Tang. Targeting loss of MTAP expression in glioblastoma multiforme with a combination of 2-fluoroadenine and methylthioadenosine [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 3835.
Clinical Consequences of Cardiomyopathy in Children With Biliary Atresia Requiring Liver Transplantation
Authors: Noelle M. Gorgis, Curtis Kennedy, Fong Lam, Kathleen Thompson, Jorge Coss‐Bu, Ayse Akcan Arikan, Trung Nguyen, Kathleen Hosek, Tamir Miloh, Saul J. Karpen, Daniel J. Penny, John Goss, Moreshwar S. Desai
Journal: Hepatology (2018)

Cirrhotic cardiomyopathy (CCM), a comorbidity of end‐stage cirrhotic liver disease, remains uncharacterized in children, largely because of a lack of an established pediatric definition. The aim of this retrospective cohort analysis is to derive objective two‐dimensional echocardiographic (2DE) criteria to define CCM associated with biliary atresia (BA), or BA‐CCM, and correlate presence of BA‐CCM with liver transplant (LT) outcomes in this population. Using receiver operating characteristic (ROC) curve analysis, optimal cut‐off values for left ventricular (LV) geometrical parameters that were highly sensitive and specific for the primary outcomes: A composite of serious adverse events (CSAE) and peritransplant death were determined. These results were used to propose a working definition for BA‐CCM: (1) LV mass index (LVMI) ≥95 g/m 2.7 or (2) relative wall thickness of LV ≥0.42. Applying these criteria, BA‐CCM was found in 34 of 69 (49%) patients with BA listed for LT and was associated with increased multiorgan dysfunction, mechanical and vasopressor support, and longer intensive care unit (ICU) and hospital stays. BA‐CCM was present in all 4 waitlist deaths, 7 posttransplant deaths, and 20 patients with a CSAE ( P &lt; 0.01). On multivariable regression analysis, BA‐CCM remained independently associated with both death and a CSAE ( P &lt; 0.01). Utilizing ROC analysis, LVMI was found to be a stronger predictor for adverse outcomes compared with current well‐established markers, including Pediatric End‐Stage Liver Disease (PELD) score. Conclusion: BA‐CCM is highly sensitive and specific for morbidity and mortality in children with BA listed for LT. 2DE screening for BA‐CCM may provide pertinent clinical information for prioritization and optimal peritransplant management of these children.
Abstract 1793: Gastrin-releasing peptide causes transactivation of the EGFR and HER2 in non-small cell lung cancer cells
Authors: Terry W. Moody, Irene Ramos Alvarez, Robert T. Jensen
Journal: Cancer Research (2018)

Abstract Gastrin releasing peptide (GRP) is a 27 amino acid peptide which is present in many lung cancer cell lines (Moody et al., Science 1981; 214: 1246). High expression of the GRP receptor (R) is associated with advanced non-small cell lung cancer (NSCLC) (Mattei et al., Arch Pathol Lab Med 2014; 138: 98). GRP stimulates but the GRPR antagonist PD176252 inhibits the proliferation of NSCLC cells (Moody et al., Eur J Pharmacol 2003; 474: 21). Here the effects of GRP on the transactivation of the EGFR and HER2 were investigated in NSCLC cells. Six of 8 NSCLC tested had GRP-R mRNA whereas all the NSCLC cells had EGFR and HER2 mRNA. Addition of GRP to NCI-H1299 cells elevated cytosolic Ca2+, increased tyrosine phosphorylation of the ERK, EGFR and HER2 and increased colony number. The effects of GRP were blocked by PD176252. The transactivation of the EGFR and HER2 was inhibited by gefitinib (EGFR tyrosine kinase inhibitor (TKI)), lapatinib (EGFR and HER2 TKI), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), N-acetylcysteine (anti-oxidant) and transforming growth factor TGF) α antibody. By ELISA, GRP increased secretion of TGFα from lung cancer cells. PD176252, gefitinib, lapatinib and trastuzumab inhibited NSCLC growth. Activation of the GRPR in NSCLC cells may facilitate the formation of EGFR homodimers and EGFR/HER2 heterodimers. Citation Format: Terry W. Moody, Irene Ramos Alvarez, Robert T. Jensen. Gastrin-releasing peptide causes transactivation of the EGFR and HER2 in non-small cell lung 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 1793.
Randomized Comparison of Antiarrhythmic Drug Therapy With Implantable Defibrillators in Patients Resuscitated From Cardiac Arrest
Authors: Karl-HeinzKuck, RiccardoCappato, JürgenSiebels, RudolfRüppel
Journal: Circulation (2000)

Background—We conducted a prospective, multicenter, randomized comparison of implantable cardioverter-defibrillator (ICD) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias. Methods and Results—From 1987, eligible patients were randomized to an ICD, amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents randomization ratio 1:3). Assignment to propafenone was discontinued in March 1992, after an interim analysis conducted in 58 patients showed a 61% higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months. The study continued to recruit 288 patients in the remaining 3 study groups; of these, 99 were assigned to ICDs, 92 to amiodarone, and 97 to metoprolol. The primary end point was all-cause mortality. The study was terminated in March 1998, when all patients had concluded a minimum 2-year follow-up. Over a mean follow-up of 57±34 months, the crude death rates were 36.4% (95% CI 26.9% to 46.6%)...
Abstract 14092: Physiological Balance Between Nitric Oxide and Endothelium-dependent Hyperpolarization Plays Important Roles in Microvascular Homeostasis in Mice
Authors: Shigeo Godo, Shuhei Tanaka, Akiyo Ito, Yosuke Ikumi, Hiroaki Shimokawa
Journal: Circulation (2016)

Introduction: Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel-size-dependent manner; NO...
Increased Collagen Deposition and Diastolic Dysfunction but Preserved Myocardial Hypertrophy After Pressure Overload in Mice Lacking PKCε
Authors: GunnarKlein, ArndSchaefer, DeniseHilfiker-Kleiner, DagmarOppermann, PraphullaShukla, AnjaQuint, EvaPodewski, AndresHilfiker, FrankSchröder, MichaelLeitges, HelmutDrexler
Journal: Circulation Research (2005)

Overexpression and activation of protein kinase C-e (PKCe) results in myocardial hypertrophy. However, these observations do not establish that PKCe is required for the development of myocardial hypertrophy. Thus, we subjected PKCe-knockout (KO) mice to a hypertrophic stimulus by transverse aortic constriction (TAC). KO mice show normal cardiac morphology and function. TAC caused similar cardiac hypertrophy in KO and wild-type (WT) mice. However, KO mice developed more interstitial fibrosis and showed enhanced expression of collagen Iα1 and collagen III after TAC associated with diastolic dysfunction, as assessed by tissue Doppler echocardiography (Ea/Aa after TAC: WT 2.1±0.3 versus KO 1.0±0.2; P<0.05). To explore underlying mechanisms, we analyzed the left ventricular (LV) expression pattern of additional PKC isoforms (ie, PKCα, PKCβ, and PKCδ). After TAC, expression and activation of PKCδ protein was increased in KO LVs. Moreover, KO LVs displayed enhanced activation of p38 mitogen-activated protein kin...