tbuckley/cabot-search huggingface dataset:
Association of Radiotherapy With Survival in Women Treated for Ductal Carcinoma In Situ With Lumpectomy or Mastectomy
Authors: Vasily Giannakeas, Victoria Sopik, Steven A. Narod
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Patients with ductal carcinoma in situ (DCIS) are treated with radiotherapy to reduce their risk of local invasive recurrence after breast-conserving surgery. However, the association of radiotherapy with breast cancer survival in patients with DCIS has not yet been clearly established. <h3>Objective</h3> To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in a large cohort of patients treated for DCIS, using a propensity score–based matching approach. <h3>Design, Setting, and Participants</h3> This cohort study of women who had first primary DCIS diagnosed between 1998 and 2014 used data from the Surveillance, Epidemiology, and End Results 18 registries database. Information on age and year of diagnosis, ethnicity, income, tumor size, tumor grade, estrogen receptor status, all treatments (surgery and radiation), and outcomes (invasive local recurrence and death from breast cancer) was abstracted for 140 366 women diagnosed with first primary DCIS. Three separate comparisons were performed using 1:1 matching: lumpectomy with radiation vs lumpectomy alone; lumpectomy alone vs mastectomy; and lumpectomy with radiation vs mastectomy. <h3>Exposures</h3> Use of radiotherapy and/or extent of surgery. <h3>Main Outcomes and Measures</h3> Crude and adjusted 15-year breast cancer–specific mortality. <h3>Results</h3> Of the 140 366 patients with DCIS in the cohort (109 712 [78.2%] white; mean [SD] age, 58.8 [12.3] years), 35 070 (25.0%) were treated with lumpectomy alone, 65 301 (46.5%) were treated with lumpectomy and radiotherapy, and 39 995 (28.5%) were treated with mastectomy. The actuarial 15-year breast cancer mortality rate was 2.33% for patients treated with lumpectomy alone, 1.74% for patients treated with lumpectomy and radiation, and 2.26% for patients treated with mastectomy. The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy vs lumpectomy alone (29 465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone vs lumpectomy alone (20 832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy vs mastectomy (29 865 propensity-matched pairs). <h3>Conclusions and Relevance</h3> In patients with DCIS, treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality compared with either lumpectomy alone or mastectomy alone. This suggests that the survival benefit of radiation is likely not due to local control, but rather to systemic effects.
Abstract 2540: TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma
Authors: Deguan Lv, Yanxin Li, Weiwei Zhang, Angel A. Alvarez, Jianming Tang, Bo Hu, Shi-Yuan Cheng, Haizhong Feng
Journal: Cancer Research (2018)

Abstract Aberrant amplification and mutations of epidermal growth factor receptor (EGFR) are the most common oncogenic events in glioblastoma (GBM), but the mechanisms by which they promote aggressive pathogenesis are not well understood. Here, we determine that non-canonical histone signature acetylated H3 lysine 23 (H3K23ac)-binding protein tripartite motif-containing 24 (TRIM24) is upregulated in clinical GBM specimens and required for EGFR-driven tumorigenesis. In multiple glioma cell lines and patient-derived glioma stem cells (GSCs), EGFR signaling promotes H3K23 acetylation and association with TRIM24. Consequently, TRIM24 functions as a transcriptional co-activator and recruits STAT3, leading to stabilized STAT3-chromatin interactions and subsequent activation of STAT3 downstream signaling, thereby enhancing EGFR-driven tumorigenesis. Our findings uncover a pathway in which TRIM24 functions as a signal relay for oncogenic EGFR signaling and suggest TRIM24 as a potential therapeutic target for GBM that are associated with EGFR activation. Citation Format: Deguan Lv, Yanxin Li, Weiwei Zhang, Angel A. Alvarez, Jianming Tang, Bo Hu, Shi-Yuan Cheng, Haizhong Feng. TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma [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 2540.
Expression of Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 in Human Atherosclerotic Lesions
Authors: HiroharuKataoka, NoriakiKume, SusumuMiyamoto, ManabuMinami, HideakiMoriwaki, TakatoshiMurase, TatsuyaSawamura, TomohMasaki, NobuoHashimoto, ToruKita
Journal: Circulation (1999)

Background—Oxidized LDL (Ox-LDL) seems to play key roles in atherogenesis. Lectinlike Ox-LDL receptor-1 (LOX-1) is a recently identified cell-surface receptor for Ox-LDL. The relationship of this novel receptor for Ox-LDL to atherogenesis, however, has not yet been clarified. In this study, we explored the expression of LOX-1 in the atherosclerotic lesions of human carotid arteries. Methods and Results—Using carotid endarterectomy specimens obtained from 21 patients and 2 samples of normal human aortas, we examined LOX-1 expression by reverse transcription–polymerase chain reaction and immunohistochemistry. In aortas without atherosclerosis, LOX-1 expression was undetectable by immunohistochemistry and negligible by reverse transcription–polymerase chain reaction. In carotid arteries, luminal endothelial cells covering early atherosclerotic lesions were more frequently positive for LOX-1 expression than those in advanced atherosclerotic lesions. Endothelial cells in the intimal neovasculature of advanced ...
Letter by Murzi and Glauber Regarding Article, “Extensive Primary Repair of the Thoracic Aorta in Acute Type A Aortic Dissection by Means of Ascending Aorta Replacement Combined With Open Placement of Triple-Branched Stent Graft: Early Results”
Authors: MicheleMurzi, MattiaGlauber
Journal: Circulation (2011)
Effect of Changes in Limb Posture on Peripheral Blood Flow
Authors: Peterbeaconsfield, Jeanginsburg
Journal: Circulation Research (1955)

Venous occlusion plethysmography was used to measure the effect of changes in limb position on the peripheral blood flow. The validity of the method with the limb dependent was investigated, and found to be reliable in the conditions of the experiment. The blood flow in the limb was found to be decreased when it was raised or lowered 45 degrees. At 15 degrees of elevation, the flow was increased. Similar changes were found in recently sympathectomized limbs. The reactions may therefore be regarded as local vascular responses to postural change.
Ian Alexander Ruthven-Stuart
Authors: Nicholas Ruthven-Stuart, Sarah Ruthven-Stuart, David Ruthven-Stuart, Peter Ruthven-Stuart, Sophie Ruthven-Stuart
Journal: BMJ (2018)

As a student Ian Alexander Ruthven-Stuart travelled to Vassar Brothers Hospital in Poughkeepsie, USA, where he found himself in nominal charge of a medical ward with acute poliomyelitis, some patients being in “iron lungs.” After returning to complete his final year in Edinburgh and winning the Watson Jones prize, he went on wto the Royal Infirmary under the guidance of Watty Mercer, professor of orthopaedics. This …
Relationships Between Low-Density Lipoprotein Particle Size, Plasma Lipoproteins, and Progression of Coronary Artery Disease
Authors: JuhaVakkilainen, GeorgeSteiner, Jean-ClaudeAnsquer, FrancoisAubin, StephanieRattier, ChristelleFoucher, AndersHamsten, Marja-RiittaTaskinen
Journal: Circulation (2003)

Background— The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes. We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease (CAD). Methods and Results— A total of 418 subjects with type 2 diabetes were randomly assigned to 200 mg micronized fenofibrate daily or placebo. The mean follow-up time was 39.6 months. LDL peak particle diameter (LDL size) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study. Progression of CAD was measured with quantitative coronary angiography. LDL size increased significantly more in the fenofibrate group than in the placebo group (0.98±1.04 versus 0.32±0.92 nm, P<0.001). In the combined group, small LDL size was significantly associated with progression of CAD measured as the...
MicroRNAs and Stem Cells
Authors: Eva-MarieHeinrich, StefanieDimmeler
Journal: Circulation Research (2012)

Stem cells hold great promise for regenerative medicine and the treatment of cardiovascular diseases. The mechanisms regulating self-renewal, pluripotency, and differentiation are not fully understood. MicroRNAs (miRs) are small noncoding RNAs controlling gene expression, either by inducing mRNA degradation or by blocking mRNA translation. The expression of miRs was shown to regulate various aspects of stem cell functions, including the maintenance and induction of pluripotency for reprogramming. In addition, some miRs control cell fate decisions. This review summarizes the role of miRs in reprogramming and embryonic stem cell self-renewal, and specifically addresses the regulation of cardiovascular cell fate decisions by miRs.
Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis
Authors: Patrick E. Nyman, Darya Buehler, Paul F. Lambert
Journal: Clinical Cancer Research (2018)

Head and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption, and high-risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC. NOTCH1 is among the most frequently mutated genes in both HPV-positive and HPV-negative HNSCC. These mutations are predicted to inactivate the function of Notch. Other studies have argued the opposite-Notch signaling is increased in HNSCC.To assess the role of Notch signaling in HPV-positive and HPV-negative HNSCC, we utilized genetically engineered mouse (GEM) models for conventional keratinizing HNSCC, in which either HPV16 E6 and E7 oncoproteins or a gain-of-function mutant p53 are expressed, and in which we inactivated canonical Notch signaling via expression of a dominant negative form of MAML1 (DNMAML1), a required transcriptional coactivator of Notch signaling.Loss of canonical Notch signaling increased tumorigenesis in both contexts and also caused an increase in nuclear β-catenin, a marker for increased tumorigenic potential. When combined with loss of canonical Notch signaling, HPV oncogenes led to the highest frequency of cancers overall and the largest number of poorly differentiated (high-grade) cancers.These findings inform on the contribution of loss of canonical Notch signaling in head and neck carcinogenesis.
Abstract 17457: Does Additional Complex Fractionated Atrial Elecrogram Guided Ablation After Linear Ablation Improve Clinical Outcome of Catheter Ablation for Longstanding Persistent Atrial Fibrillation? A Prospective Randomized Study
Authors: Tae-Hoon Kim, Jae-Sun Uhm, Jong-Youn Kim, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2015)

Introduction: Although long-lasting circumferential pulmonary vein isolation (CPVI) is a corner stone of catheter ablation for atrial fibrillation (AF), it is not clear whether additional linear or complex fractionated atrial electrogram (CFAE)-guided ablations improve clinical outcome in patients with long-standing persistent AF (L-PeAF). Hypothesis: The purposes of this study were to compare CFAE maps before and after linear ablation, and to test whether additional CFAE ablation after linear ablation improves clinical outcome of L-PeAF. Methods: This study enrolled 119 consecutive L-PeAF patients (male 72.8%, 61.7±10.6 years old) who underwent RFCA. After baseline CFAE mapping, we conducted CPVI and linear ablations (posterior box lesion and anterior line). If AF maintained after linear ablation, we mapped CFAE again, and randomly assigned the patients to linear ablation group (Line, n=45) and additional CFAE ablation group (CFAE+Line, n=48). The patients whose AF terminated or changed to AT were excluded from randomization and classified as AF-Stop group (n=26). We compared pre- and post-linear ablation CFAE maps and clinical outcomes of CFAE+Line, Line, and AF-Stop groups. Results: 1. Mean CFAE-cycle length (CL) was significantly prolonged (203.65±40.35 ms to 264.17±39.03 ms, p&lt;0.001) and CFAE area was reduced (15.49±14.95% to 7.95±9.36%, p&lt;0.001) after linear ablation. Post-linear ablation CFAE was mainly located at left atrial (LA) appendage, septum, and posterior inferior LA. 2. There were no differences in total procedure time (p=0.441), ablation time (p=0.144), and procedure-related complication rate (p=0.955) among three groups. 3. During 17.4±10.5 month follow-up period, clinical recurrence rates were 30.4% in CFAE+Line group, 12.8% in Line group, and 16.7% in AF-Stop groups, respectively (Log rank, p=0.138). 4. Additional CFAE ablation after linear ablation did not improve clinical outcome of catheter ablation at all in patients with L-PeAF (HR 2.11, 95% CI 0.91 - 4.89, p=0.082). Conclusions: Linear ablation prolonged CFAE-CL and localized CFAE area in patients with L-PeAF. However, CFAE guided ablation in addition to linear ablation and CPVI did not improve clinical outcome of catheter ablation.
Immune checkpoint inhibitor treatment of advanced age metastatic melanoma (MM) patients.
Authors: Upendra P. Hegde, Phil Kerr, Sophie Masternak, Bruce Mark Brenner, Jane grant-Kels
Journal: Journal of Clinical Oncology (2017)

e14603 Background: Immune checkpoint inhibitor (ICI) treatment has become effective method of treating mm including in those over 65 years of age. Increasing number of advanced age mm patients (pts.) are eligible for ICI treatment but not much is known about its efficacy and safety in relation to senescent immune system. We are reporting our updated experience of ICI treatment of advanced age mm pts. from a single Institute. Methods: Between 2011 and 2016, 32 eligible pts. diagnosed with mm were treated at the University of Connecticut with ICI including anti CTLA-4 antibody Ipilimumab, anti PD-1 antibody Pembrolizumab or combination of Ipilimumab and Nivolumab at their FDA approved doses on a standard protocol. Pts. were monitored for immune related adverse events (irAE) that were graded and managed with standard immune suppressive regimens Results: 12 out of 32 mm pts. were over 70 years of age (median 82.5 years, range 73-88 years). Nine pts. were treatment naïve, two had previously failed Ipilimumab treatment and one anti-BRAF and anti- MEK targeted therapy. Clinical benefit occurred in 5 out of 12 pts. (Complete response (CR) 3, partial response 1 and stable disease 1). Nine out of 12 pts. developed irAE that included three grade II (fatigue, diarrhea, hypopituitarism each) and 6 grade IV events (skin rash-1, colitis-1, encephalopathy-1, myasthenia gravis-1, and pneumonitis in 2 pts. each respectively). Of note, an 87-year-old male developed polymyalgia rheumatica after second dose of anti PD-1 treatment that responded to steroids, but developed autoimmune diabetes mellitus and pneumonitis following third dose. Two pts. died from irAE that included an 87-year-old woman from treatment refractory myasthenia gravis and 77-year-old male who suffered sudden death during steroid treatment of pneumonitis. Six pts. died of progressive disease including sudden death in a 77-year old woman and a 87-year-old male following five and two anti PD-1 treatments respectively. One pt. died from pulmonary embolism and four pts. are alive, 2 in CR and two with disease. Conclusions: Our experience indicate advanced age mm pts. respond to ICI treatment but have heightened risk of developing serious irAEs.
Abstract 13016: Tissue Mitral Annular Displacement (TMAD) Predicts Long-term Prognosis in Heart Failure Patients Receiving Cardiac Resynchronization Therapy
Authors: KatsuomiIwakura, AtsunoriOkamura, YasushiKoyama, MotooDate, KoichiInoue, HiroyukiNagai, YukoToyoshima, KojiTanaka, TakafumiOka, NobuakiTanaka, YukoYamanaka, TomohiroYamasaki, TomoakiOkada, YoheiSotomi, KoheiAzuma, YoshiyukiOrihara, SatoshiKameda, MutsumiIwamoto, YoshihiroOta, KenshiFujii
Journal: Circulation (2014)

Introduction: Assessment of left ventricular (LV) dyssynchrony by echocardiography has only a limited ability to predict response to cardiac resynchronizing therapy (CRT) because of high variability of the measurement.Tissue mitral annular displacement (TMAD) is a rapid and robust method for the assessment of left ventricular (LV) longitudinal deformity. We previously reported that TMAD predicts good responders to CRT among patients with severe heart failure (AHA scientific meeting 2012). In the present study, we investigated whether TMAD could predict the long-term prognosis after CRT implantation. Methods: We performed echocardiography study in 41 patients with dilated cardiomyopathy (DCM) before and at 6 month of CRT, using iE33 (Philips Medical Systems). TMAD was measured on an apical 4-chamber image using QLAB software (Philips Medical Systems) to assess the movement of septal- and lateral part of mitral annulus toward apex. We measured the interval between QRS complex to peak of displacement on both...
Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility
Authors: IstvánSzokodi, PasiTavi, GáborFöldes, SariVoutilainen-Myllylä, MikaIlves, HeikkiTokola, SampsaPikkarainen, JarkkoPiuhola, JaanaRysä, MiklósTóth, HeikkiRuskoaho
Journal: Circulation Research (2002)

The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, the functional importance of apelin in the cardiovascular system is not known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L) induced a dose-dependent positive inotropic effect (EC50: 33.1±1.5 pmol/L). Moreover, preload-induced increase in dP/dtmax was significantly augmented (P<0.05) in the presence of apelin. Inhibition of phospholipase C (PLC) with U-73122 and suppression of protein kinase C (PKC) with staurosporine and GF-109203X markedly attenuated the apelin-induced inotropic effect (P<0.001). In addition, zoniporide, a selective inhibitor of Na+-H+ exchange (NHE) isoform-1, and KB-R7943, a potent inhibitor of the reverse mode Na+-Ca2+ exchange (NCX), significantly suppressed the response to apelin (P<0.001). Perforated patch-clamp recordings showed that apelin did not modulate L-type Ca2+ current or voltage-activated K+ currents in iso...
Abstract 11063: Evaluation of Different Energy Drinks and Coffee on Endothelial Function
Authors: John C Somberg, Janos Molnar
Journal: Circulation (2015)

Background: Endothelial function is an important component of vascular health. There have been differing reports on the effect of energy drink on endothelial function. The aim of this study was to evaluate the effect of 3 commonly consumed energy drinks on endothelial function. As the main active ingredient of energy drinks is caffeine, a comparison was made to coffee, a drink with substantial caffeine content. The hypothesis tested was that energy drinks differ in effect on endothelial function due to differing ingredients. Methods: Endothelial function was evaluated in 16 healthy volunteers employing an EndoPAT device (Itamar Medical, Israel) that measures digital peripheral arterial tonometry and reports endothelial function as the Reactive Hyperemia Index (RHI). Volunteers (Age: 25±5 years, 7 females, 9 male, weight: 72±11 kg, height: 169±10 cm, systolic blood pressure: 121±7 mmHg, and diastolic blood pressure: 80±6 mmHg) received the energy drink sequence (3) or coffee (16). Energy drink or coffee were given at least 2 days apart. Drinks studied were 250 mL Red Bull containing 80 mg caffeine, 57 mL “5-hour Energy” containing 230 mg caffeine, a can of 355 mL “NOS” energy drink containing 120 mg caffeine and a cup of 473 mL coffee containing 240 mg caffeine, taken in a random order. Studies were performed before drink (baseline) at 1.5 and 4 hrs. post drink. Results: Two of the energy drinks (Red Bull and 5-hour Energy) significantly improved endothelial function at 4 hrs. post drink, while one (NOS) as well as coffee did not change endothelial function significantly. RHI increased by 40±7% (p=0.01) and 48±12% (p=0.019) following 5-hour Energy and Red Bull respectively. RHI decreased following NOS by 13±8% (p=0.101) and increased by 7±30% (p=1.000) following coffee. Conclusion: Improvement in endothelial function as measured by RHI is seen with some but not all energy drinks. Coffee does not show a significant improvement in endothelial function as measured by RHI.
Aldosterone Production Is Activated in Failing Ventricle in Humans
Authors: YujiMizuno, MichihiroYoshimura, HirofumiYasue, TomohiroSakamoto, HisaoOgawa, KiyotakaKugiyama, EisakuHarada, MasafumiNakayama, ShotaNakamura, TeruhikoIto, YukioShimasaki, YoshihikoSaito, KazuwaNakao
Journal: Circulation (2001)

Background—Recent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart. Methods and Results—Plasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysfunction (LVDD), and 23 control subjects. Aldosterone levels were significantly higher in AIV and CS than Ao in LVSD (98±10 versus 72±9 pg/mL, P<0.001, and 97±11 versus 72±9 pg/mL, P<0.001, respectively) and LVDD (87±10 versus 71±9 pg/mL, P<0.01, and 84±10 versus 71±9 pg/mL, P<0.01, respectively) groups, but no differences were observed in levels for these sites in the control group. Levels of ACE activity and BNP also were higher in AIV than Ao in both LV dysfunction groups. The difference in aldosterone levels betwe...
Effects of a K+ Channel Opener to Reduce Transmural Dispersion of Repolarization and Prevent Torsade de Pointes in LQT1, LQT2, and LQT3 Models of the Long-QT Syndrome
Authors: WataruShimizu, CharlesAntzelevitch
Journal: Circulation (2000)

Background—This study examines the effects of nicorandil, a K+ channel opener, on transmural dispersion of repolarization (TDR) and induction of torsade de pointes (TdP) under conditions mimicking the LQT1, LQT2, and LQT3 forms of the congenital long-QT syndrome (LQTS). Methods and Results—Transmembrane action potentials of epicardial, M, and endocardial cells were recorded simultaneously from an arterially perfused wedge of canine left ventricle together with a transmural ECG. Chromanol 293B (30 μmol/L) was used to block IKs (LQT1 model). Isoproterenol (50 to 100 nmol/L) was used to mimic an increase in β-adrenergic tone, d-sotalol (100 μmol/L) to block IKr (LQT2 model), and ATX-II (20 nmol/L) to augment late INa (LQT3 model). Isoproterenol+chromanol 293B, d-sotalol, and ATX-II produced preferential prolongation of the action potential duration at 90% repolarization (APD90) of the M cell, an increase of TDR, and spontaneous as well as stimulation-induced TdP (LQT1, 3/6; LQT2, 3/6; LQT3, 5/6). Nicorandil ...