tbuckley/cabot-search huggingface dataset:
The Anti-HER3 mAb Seribantumab Effectively Inhibits Growth of Patient-Derived and Isogenic Cell Line and Xenograft Models with Oncogenic <i>NRG1</i> Fusions
Authors: Igor Odintsov, Allan J.W. Lui, Whitney J. Sisso, Eric Gladstone, Zebing Liu, Lukas Delasos, Renate I. Kurth, Exequiel M. Sisso, Morana Vojnic, Inna Khodos, Marissa S. Mattar, Elisa de Stanchina, Shawn M. Leland, Marc Ladanyi, Romel Somwar
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Oncogenic fusions involving the neuregulin 1 (NRG1) gene are found in approximately 0.2% of cancers of diverse histologies. The resulting chimeric NRG1 proteins bind predominantly to HER3, leading to HER3-HER2 dimerization and activation of downstream growth and survival pathways. HER3 is, therefore, a rational target for therapy in NRG1 fusion–driven cancers. Experimental Design: We developed novel patient-derived and isogenic models of NRG1-rearranged cancers and examined the effect of the anti-HER3 antibody, seribantumab, on growth and activation of signaling networks in vitro and in vivo. Results: Seribantumab inhibited NRG1-stimulated growth of MCF-7 cells and growth of patient-derived breast (MDA-MB-175-VII, DOC4-NRG1 fusion) and lung (LUAD-0061AS3, SLC3A2-NRG1 fusion) cancer cells harboring NRG1 fusions or NRG1 amplification (HCC-95). In addition, seribantumab inhibited growth of isogenic HBEC cells expressing a CD74-NRG1 fusion (HBECp53-CD74-NRG1) and induced apoptosis in MDA-MB-175-VII and LUAD-0061AS3 cells. Induction of proapoptotic proteins and reduced expression of the cell-cycle regulator, cyclin D1, were observed in seribantumab-treated cells. Treatment of MDA-MB-175-VII, LUAD-0061AS3, and HBECp53-CD74-NRG1 cells with seribantumab reduced phosphorylation of EGFR, HER2, HER3, HER4, and known downstream signaling molecules, such as AKT and ERK1/2. Significantly, administration of seribantumab to mice bearing LUAD-0061AS3 patient-derived xenograft (PDX) and OV-10-0050 (ovarian cancer with CLU-NRG1 fusion) PDX tumors induced regression of tumors by 50%–100%. Afatinib was much less effective at blocking tumor growth. Conclusions: Seribantumab treatment blocked activation of the four ERBB family members and of downstream signaling, leading to inhibition of NRG1 fusion–dependent tumorigenesis in vitro and in vivo in breast, lung, and ovarian patient-derived cancer models.
The safety of maximal exercise testing.
Authors: LGibbons, S NBlair, H WKohl, KCooper
Journal: Circulation (1989)

Previous reports on the safety of exercise testing have been based on surveys from different testing facilities with a variety of testing protocols and patient types. From 1971 through 1987, 71,914 maximal exercise tests conducted in a population with a low prevalence of known coronary heart disease under uniform conditions at a single medical facility resulted in six major cardiac complications including one death. No complications have occurred in the past 10 years in 45,000 maximal tests. The overall cardiac complication rate in men and women is 0.8 complications per 10,000 tests with 95% confidence intervals of 0.3-1.9 complications per 10,000 tests. Maximal exercise testing appears safer than some previously published reports have suggested and seems to be getting safer with time.
Focus on the Number of Radiation Oncology Trials or on Clinical Relevance?
Authors: Cyrus Chargari, Christophe Massard, Eric Deutsch
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Lung Cancer in Republic of China
Authors: Yung-Hung Luo, Chao-Hua Chiu, Chih-Hsi Scott Kuo, Teh-Ying Chou, Yi-Chen Yeh, Han-Shui Hsu, Sang-Hue Yen, Yuan-Hung Wu, James Chih-Hsin Yang, Bin-Chi Liao, Te-Chun Hsia, Yuh-Min Chen
Journal: Journal of Thoracic Oncology (2021)
A computer graphic-based angiographic model for normal left ventricular contraction in man and its application to the detection of abnormalities in regional wall motion.
Authors: T HShepertycki, B CMorton
Journal: Circulation (1983)

Analyzing the digitized left ventricular cineangiograms of 70 patients with no demonstrable heart disease (NDHD), we derived an angiographic model for normal contraction in the intact heart as viewed in the 30 degree right anterior oblique projection. This model was verified statistically by comparing the predicted regional stroke volumes with the measured volumes for the NDHD group. A wall motion system based on this model was compared with four other systems by examining the ventriculograms of 141 patients, all suffering from coronary artery disease but with normal volumes and ejection fractions (greater than 0.61). Of these, 60 had normally contracting ventricles and 81 exhibited mild regional abnormalities according to two experienced angiographers. Using Cochrane's Q test, we found significant differences among the five methods (Q = 29.5;p less than .001). The new approach showed significantly better agreement with the subjective assessment than the next best method (Q = 5.3;p less than .05). On a re...
Catecholamines in coronary sinus and peripheral plasma during pacing-induced angina in man.
Authors: LSchwartz, M JSole, E FVaughan-Neil, N MHussain
Journal: Circulation (1979)

We measured aortic and coronary sinus dopamine (DA), epinephrine (E), and norepinephrine (NE) in eight patients with cardiac ischemia (I) and eight control subjects (C). Samples were taken at rest (73 +/- 3 beats/min in C and 68 +/- 3 beats/min in I) and during coronary sinus pacing to peak rates (144 +/- 4 beats/min in C and 136 +/- 6 beats/min in I). Arterial NE was higher in the ischemic patients at rest (254 +/- 25 pg/ml in C and 324 +/- 21 in I; p less than 0.05). There were no differences in arterial E and DA. Neither pacing nor angina affected peripheral catecholamine concentrations. Resting myocardial NE flux was similar for both groups. With pacing, coronary sinus flow and net myocardial NE release increased significantly in both groups. The maximum relative increase in net myocardial NE release was less in the ischemic patients than in the controls (575 +/- 145% in C and 255 +/- 40% in I; p less than 0.05). Thus, angina induced by pacing does not augment peripheral sympathetic activity. Furtherm...
Comparative evaluation of the IBM (12-lead) and Royal Infirmary (orthogonal three-lead) ECG computer programs.
Authors: P WMacfarlane, D IMelville, M RHorton, J JBailey
Journal: Circulation (1981)

A comparison of two computer programs for ECG interpretation was undertaken. Twelve-lead ECGs from 300 patients with various clinical abnormalities were interpreted at the National Institutes of Health using version 1 of the IBM program and corresponding orthogonal three-lead ECGs were analyzed by the Glasgow Royal Infirmary (GRI) program. Interpretations were compared with respect to the clinical documentation, wherever possible, and with each other directly in the case of diagnostic statements for which non-ECG documentation was not available. The two programs had a similar performance in determining abnormalities such as myocardial infarction and ventricular hypertrophy. However, with respect to conduction defects and ST-T-wave statements, certain discrepancies between the two program performances were revealed. There were 222 disagreements between various diagnostic statements. GRI was judged correct in 119 of these disagreements and IBM in 70. In these 189 cases the disagreement could most often be a...
Tubuloglomerular Feedback Synchronization in Nephrovascular Networks
Authors: Tayyaba Zehra, William A. Cupples, Branko Braam
Journal: Journal of the American Society of Nephrology (2021)

To perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by the generic myogenic response and the kidney-specific tubuloglomerular feedback (TGF) mechanism. The central theme of this paper is that, to achieve autoregulation, nephrons do not work as single units to manage their individual blood flows, but rather communicate electrically over long distances to other nephrons via the vascular tree. Accordingly, we define the nephrovascular unit (NVU) to be a structure consisting of the nephron, glomerulus, afferent arteriole, and efferent arteriole. We discuss features that require and enable distributed autoregulation mediated by TGF across the kidney. These features include the highly variable topology of the renal vasculature which creates variability in circulation and the potential for mismatch between tubular oxygen demand and delivery; the self-sustained oscillations in each NVU arising from the autoregulatory mechanisms; and the presence of extensive gap junctions formed by connexins and their properties that enable long-distance transmission of TGF signals. The existence of TGF synchronization across the renal microvascular network enables an understanding of how NVUs optimize oxygenation-perfusion matching while preventing transmission of high systemic pressure to the glomeruli, which could lead to progressive glomerular and vascular injury.
No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon.
Authors: RSchulz, B DGuth, GHeusch
Journal: Circulation (1991)

BACKGROUNDThe hypothesis that increases in coronary perfusion increase ventricular performance independently from providing enhanced oxygen supply (Gregg phenomenon) remains controversial.METHODS AND RESULTSTo study the physiological significance of changes in coronary perfusion on global and regional myocardial function in situ, the left anterior descending coronary artery of isoflurane-anesthetized swine was cannulated, and perfusion was varied. In one group of swine (n = 5), coronary arterial pressure was increased in four steps from 88 +/- 11 to 186 +/- 11 mm Hg by increasing the speed of the pump circuit providing coronary blood flow. No changes in left ventricular end-diastolic pressure, peak pressure, or maximum left ventricular dP/dt were observed. Subendocardial blood flow (by radiolabeled microspheres) increased from 0.96 +/- 0.27 to 2.04 +/- 0.73 ml/min/g without any increase in systolic wall thickening (by sonomicrometry) or myocardial oxygen consumption of the anterior myocardium. In a seco...
Chronic one-kidney hypertension in rabbits. II. Evidence for a new factor.
Authors: L TSkeggs, J RKahn, MLevine, F EDorer, K ELentz
Journal: Circulation Research (1976)

The arterial pressure of rabbits with chronic one-kidney hypertension can be lowered to normotensive levels by direct immunization with preparations made from the cortex of hog kidneys. Hypertensive rabbits that are immunized with large amounts of renin may develop high plasma antirenin titers without affecting their blood pressure. Removal of renin by chromatography on columns of immobilized antirenin yields preparations with little or no renin. Such preparations may be effective in lowering blood pressure although they do not elicit the formation of plasma antirenin and the rabbits remain sensitive to challenging doses of rabbit renin. The evidence suggests that an unknown substance is responsible for the development of a cross-reacting antibody that neutralizes an unknown factor that is essential for the maintence of an elevated blood pressure level in rabbits with chronic one-kidney hypertension.
Quantitation of absolute area of a coronary arterial stenosis: experimental validation with a preparation in vivo.
Authors: JWiesel, A MGrunwald, CTobiasz, BRobin, M MBodenheimer
Journal: Circulation (1986)

The absolute cross-sectional area of a coronary stenosis measured by quantitative coronary angiography correlates well with its hemodynamic significance. We evaluated a combined approach using edge detection applied to the normal segment and videodensitometry applied to the stenosis to determine the absolute cross-sectional area of the stenosis (videodensity method). The results were then compared with those with the edge detection method applied directly to the stenosis. The area of the stenosis by the edge detection method was calculated by analyzing two orthogonal projections for irregular stenoses and with use of the formula for the area of an ellipse (ellipse method). The accuracy of both these techniques was assessed by analyzing digital angiograms acquired from closed-chest dogs in which 10 plastic cylinders with precisely machined circular and irregular lumina were inserted into the coronary arteries. Angiograms of irregular stenoses were acquired in two orthogonal views. The ellipse method applie...
Re: Apoptosis and Growth Inhibition in Malignant Lymphocytes After Treatment With Arsenic Trioxide at Clinically Achievable Concentrations
Authors: J. Huff, M. Waalkes, A. Nyska, P. Chan
Journal: JNCI Journal of the National Cancer Institute (1999)

Zhu et al.(1) indicated that "As 2 O 3 may prove useful in the treatment of malignant lymphoproliferative disorders" in general, and Kroemer and de The ´(2) concluded with the statement that "irrespective of the molecular details, it appears that arsenic constitutes a welcome addition to the clinician's armamentarium for the chemotherapy of leukemia."Their major theme centers on the mechanism of arsenic trioxide in eradicating acute promyelocytic leukemia (APL).This is a major cancer chemotherapeutic advance if proven correct.However, we believe that the use of arsenicals must be tempered by toxicologic realities (3,4).
The effects of overdrive pacing and lidocaine on atrioventricular junctional rhythm in man: the role of abnormal automaticity.
Authors: JTenczer, LLittmann, MRohla, TFenyvesi
Journal: Circulation (1985)

The effects of overdrive pacing and lidocaine were studied in 22 patients with atrioventricular (AV) junctional rhythms. Based on the responses to cardiac pacing and lidocaine, patients were divided into two groups. AV junctional rhythms in group I (17 patients) were suppressed by overdrive pacing, and their rates were decreased by lidocaine. Lidocaine also prolonged the junctional recovery time in these patients. AV junctional rhythms in group II (five patients) were not suppressed by overdrive pacing. In contrast, the rate increased after overdrive pacing. Lidocaine did not alter the basic cycle lengths or the recovery times of the AV junctional rhythms in this group of patients. The data suggest that AV junctional rhythms in group I were caused by normal automaticity, while those in group II were probably due to abnormal automaticity.
Shall The Journal be Removed to Washington?
Authors: W. W. Hester
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I am opposed to the proposition made to move the publication office and management ofThe Journalof the Association to Washington City. I voteChicagoto be continued as its permanent home because it is most central and has unexcelled mail facilities to all parts of the country, and because it is now and will continue to be nearer the centre of population, and destined to be the greatest medical centre of the United States. I would formulate a ballot and distribute to every member of the Association, requesting his vote on location, with signature and P. O. address, to be returned to the committee having the question of location in charge. This seems to be the legitimate way to satisfactorily settle the issue. 3640 Cottage Grove Ave., Chicago, Jan. 16, 1891.
Kinetics of thallium exchange in cultured rat myocardial cells.
Authors: DMcCall, L JZimmer, A MKatz
Journal: Circulation Research (1985)

The kinetics of thallium exchange in cultured rat myocardial cells were studied and compared to those of potassium in the same tissue. Studies were carried out using low concentrations (10 nM to 5 microM) of thallium-204, approximating those likely to be encountered during clinical myocardial scintigraphy. Both thallium uptake and release could be described by a single exponential with a half-time of exchange which was approximately half that of potassium and which was largely independent of extracellular thallium concentration. Some 60% of thallium uptake occurred via an  or ouabain-inhibitable mechanism which, in the absence of extracellular potassium, could be activated by low concentrations (10 nM to 5 microM) of thallium. The apparent Km for thallium on this active transport mechanism was 2-7 microM. Increasing extracellular potassium from 0-10 mM caused significant, concentration-dependent decreases in both the total and the active component of the thallium influx. Similarly nonradioactive t...
Comparison of angioplasty and surgery for unoperated coarctation of the aorta.
Authors: R EShaddy, M MBoucek, J ESturtevant, H DRuttenberg, R BJaffe, L YTani, V EJudd, L GVeasy, E CMcGough, G SOrsmond
Journal: Circulation (1993)

BACKGROUNDThe use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion.METHODS AND RESULTSThirty-six patients were prospectively randomized to either angioplasty (20 patients) or surgery (16 patients). Immediate results and patient follow-up, including physical examination, angiograms, and magnetic resonance imaging, were compared between groups. Reduction in peak systolic pressure gradient across the coarctation was similar (86%) immediately after both balloon coarctation angioplasty and surgery. On follow-up, aneurysms were seen only in the angioplasty group (20%) and not in the surgery group (0%). No aneurysms have shown progression or required surgery. The incidence of other complications was similar in both groups, although two patients experienced neurological complications after surgery. Although not statistically differen...
Rapid reduction of plasma atrial natriuretic peptide levels during percutaneous transvenous mitral commissurotomy in patients with mitral stenosis.
Authors: FIshikura, SNagata, YHirata, KKimura, SNakatani, JTamai, MYamagishi, FOhmori, SBeppu, MTakamiya
Journal: Circulation (1989)

To clarify the direct contribution of the left atrial pressure to secretion of human atrial natriuretic peptide (hANP), we have attempted to study the relations between plasma hANP levels, neurohumoral factors, and hemodynamic changes in 13 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). After PTMC, the left atrial pressure fell from 14.7 +/- 1.9 (mean +/- SEM) to 6.5 +/- 0.7 mm Hg in all patients studied (p less than 0.0005), whereas there were no remarkable changes in either the right atrial pressure, mean arterial pressure, or heart rate. Plasma immunoreactive hANP levels obtained from the pulmonary artery decreased from 278 +/- 51 to 137 +/- 31 pg/ml after PTMC (p less than 0.0005). There was a significant correlation between the decrement of hANP levels and that of left atrial pressure (r = 0.72, p less than 0.005). Neither plasma renin activity nor norepinephrine levels changed. In contrast, plasma aldosterone concentrations significantly increased fro...
Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding.
Authors: A MFeldman, E OWeinberg, P ERay, B HLorell
Journal: Circulation Research (1993)

Left ventricular hypertrophy (LVH) is associated with reinduction of the fetal program of gene expression. It is unclear whether this pattern of cardiac gene expression changes with the development of left ventricular decompensation and failure. To answer these questions, we quantified steady-state levels of mRNA by the polymerase chain reaction in the left ventricular myocardium of rats 8 and 20 weeks after ascending aortic banding. Clinical and hemodynamic assessment identified two distinct groups of animals 20 weeks after aortic banding. The first group (20-week nonfailed LVH) demonstrated substantial LVH but no depression in systolic developed pressure per gram left ventricular weight compared with the age-matched control group. In contrast, a second group of rats exhibited clinical signs of congestive failure as well as a marked diminution in left ventricular developed pressure per gram. Assessment of the levels of mRNA encoding a panel of cardiac proteins demonstrated a greater than twofold increase...
Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential.
Authors: M JGardner, T JMontague, C SArmstrong, B MHoracek, E RSmith
Journal: Circulation (1986)

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each m...
Experimental balloon valvuloplasty of fibrotic and calcific mitral valves.
Authors: NReifart, BNowak, DBaykut, PSatter, W DBussmann, MKaltenbach
Journal: Circulation (1990)

This study evaluated the mechanism of valvular area expansion during single- and double-balloon valvuloplasty in fibrotic and calcific mitral valves. Special interest was focused on the morphological features of the valves treated. Mitral valves that appeared unsuitable for commissurotomy were excised in toto at the time of mitral valve replacement in 15 patients. The excised valves were mounted in a fluid-filled chamber with a window for photographic evaluation. The chamber was perfused continuously to ensure maximal valvular opening. The valve was photographed, and the orifice area was measured before and after balloon expansion. In addition, the specimens were examined macroscopically and radiographically with regard to calcium content and degree and localization of fibrosis. These data were correlated with splitting of commissures and with rupture of leaflets. Nine valves were fibrotic, and six were calcific. Dilatation was performed first with a single-balloon catheter (diameter, 2 cm) and then with ...