tbuckley/cabot-search huggingface dataset:
Emerging mechanisms and targeted therapy of ferroptosis in cancer
Authors: Haiyan Wang, Yan Cheng, Chao Mao, Shuang Liu, Desheng Xiao, Jun Huang, Yongguang Tao
Journal: Molecular Therapy (2021)

Ferroptosis is an iron- and lipid reactive oxygen species (ROS)-dependent form of programmed cell death that is distinct from other forms of regulatory cell death at the morphological, biological, and genetic levels. Emerging evidence suggests critical roles for ferroptosis in cell metabolism, the redox status, and various diseases, such as cancers, nervous system diseases, and ischemia-reperfusion injury, with ferroptosis-related proteins. Ferroptosis is inhibited in diverse cancer types and functions as a dynamic tumor suppressor in cancer development, indicating that the regulation of ferroptosis can be utilized as an interventional target for tumor treatment. Small molecules and nanomaterials that reprogram cancer cells to undergo ferroptosis are considered effective drugs for cancer therapy. Here, we systematically summarize the molecular basis of ferroptosis, the suppressive effect of ferroptosis on tumors, the effect of ferroptosis on cellular metabolism and the tumor microenvironment (TME), and ferroptosis-inducing agents for tumor therapeutics. An understanding of the latest progress in ferroptosis could provide references for proposing new potential targets for the treatment of cancers. Ferroptosis is an iron- and lipid reactive oxygen species (ROS)-dependent form of programmed cell death that is distinct from other forms of regulatory cell death at the morphological, biological, and genetic levels. Emerging evidence suggests critical roles for ferroptosis in cell metabolism, the redox status, and various diseases, such as cancers, nervous system diseases, and ischemia-reperfusion injury, with ferroptosis-related proteins. Ferroptosis is inhibited in diverse cancer types and functions as a dynamic tumor suppressor in cancer development, indicating that the regulation of ferroptosis can be utilized as an interventional target for tumor treatment. Small molecules and nanomaterials that reprogram cancer cells to undergo ferroptosis are considered effective drugs for cancer therapy. Here, we systematically summarize the molecular basis of ferroptosis, the suppressive effect of ferroptosis on tumors, the effect of ferroptosis on cellular metabolism and the tumor microenvironment (TME), and ferroptosis-inducing agents for tumor therapeutics. An understanding of the latest progress in ferroptosis could provide references for proposing new potential targets for the treatment of cancers.
Matching between ventricle and arterial load. An evolutionary process.
Authors: GElzinga, NWesterhof
Journal: Circulation Research (1991)

The hemodynamic properties of the ventricle are related to those of the arterial load. However, the precise nature of this relation is not known. At least three different matching criteria have been described in the literature: optimization of heart rate, of power output, and of external efficiency. Although these suggestions are based on experimental findings, there is little understanding of the underlying principles. We now suggest that the balance between the ventricle and its load is a result of the evolutionary process. To support our view, three simple assumptions are proposed regarding the evolutionary determinants underlying the relation between ventricle and arterial load: 1) Arterial pressure and flow to be generated by the ventricular pump under normal (control) conditions are set by the demands of the body. 2) Mechanical properties of contractile machinery and arterial wall material are given. 3) The heart and arterial system should have minimum size. On the basis thereof, we argue that heart...
Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines.
Authors: F ERademakers, M BBuchalter, W JRogers, E AZerhouni, M LWeisfeldt, J LWeiss, E PShapiro
Journal: Circulation (1992)

BACKGROUNDEfficient early diastolic filling is essential for normal cardiac function. Diastolic suction, as evidenced by a decreasing left ventricular pressure during early filling, could result from restoring forces (the release of potential energy stored during systolic deformation) dependent on myofilament relaxation. Although these restoring forces have been envisioned within individual myofibers, recent studies suggest that gross fiber rearrangement involving the connective tissue network occurs easy in diastole. This may lead to the release of potential energy stored during systole and suction-aided filling.METHODS AND RESULTSTo establish precisely the timing and extent of restoration of the systolic torsional deformation of the left ventricle with respect to early filling at baseline and with enhanced relaxation, we studied untwisting during control conditions and with catecholamine stimulation. Using noninvasive and nondestructive magnetic resonance tagging, torsional deformation of the left ventr...
Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.
Authors: M RBristow, J BO'Connell, E MGilbert, W JFrench, GLeatherman, N EKantrowitz, JOrie, M LSmucker, GMarshall, PKelly
Journal: Circulation (1994)

BACKGROUNDSmall-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade in a heart failure population that includes ischemic dilated cardiomyopathy (ISCD).METHODS AND RESULTSBucindolol is a nonselective beta-blocking agent with mild vasodilatory properties. One hundred forty-one subjects with class II or III heart failure, left ventricular ejection fraction (LVEF) < or = 0.40, and background therapy of angiotensin-converting enzyme inhibitors, digoxin, and diuretics were given an initial challenge dose of bucindolol 12.5 mg. One hundred thirty-nine subjects (99 with IDC, 40 with ISCDC) tolerated challenge and were randomized to treatment with placebo or bucindolol 12.5 mg/d (low dose), 50 mg/d (medium dose), or 200 mg/d (high dose). At the end of 12 weeks, left ...
Working Under Pressure - Insufflation-Induced Gastric Barotrauma During Esophageal ESD
Authors: D Persyn, D Dewulf, R Bisschops
Journal: Endoscopy (2021)

A 64-year-old female underwent endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (cT1N0M0). During follow-up a stricture developed, managed with sequential balloon dilation. We also identified two metachronic lesions for which a second ESD was performed immediately after dilatation of the esophageal stricture.
Left-to-right atrial shunting after percutaneous mitral valvuloplasty. Incidence and long-term hemodynamic follow-up.
Authors: ACequier, RBonan, ASerra, IDyrda, JCrépeau, MDethy, DWaters
Journal: Circulation (1990)

To assess the incidence and long-term evolution of left-to-right atrial shunting (AS) after the performance of percutaneous mitral valvuloplasty (PMV), venovenous indicator dilution curves and right heart oximetric measurements were obtained in 68 consecutive patients before and after successful PMV. The procedure increased the mitral valve area (p less than 0.0001) and decreased the mitral gradient (p less than 0.0001). No AS was detected before PMV, but it was detected immediately after PMV. Oximetry identified AS in 17 patients (25%), and dilution curves identified AS in an additional 25 (total, 62%). The ratio of mean pulmonary to systemic blood flow (Qp/Qs) was 1.31 +/- 0.2, and in six patients (9%), the ratio was 1.5 or greater. Among nine clinical, 20 hemodynamic, and six procedural variables, stepwise logistic regression analysis selected the following as independent predictors of AS: smaller increases in valve area (p = 0.01) after PMV, absence of previous surgical commissurotomy (p = 0.02), mitr...
Vector mapping of myocardial activation.
Authors: A HKadish, J FSpear, J HLevine, R FHanich, CProod, E NMoore
Journal: Circulation (1986)

A custom-made probe, consisting of four electrodes arranged so that two orthogonal bipolar electrograms could be recorded from a single site, was used to record epicardial activity during atrial and ventricular pacing in five normal and five anesthetized open-chest mongrel dogs with myocardial infarction. Unfiltered bipolar electrograms recorded with a 2 mm interelectrode distance averaged 36 +/- 15 mV in amplitude and 16 +/- 5 msec in duration in normal areas and 14 +/- 11 mV and 23 +/- 12 msec in infarcted areas (p less than .01 infarct vs normal). The bipolar electrograms were vector summed so that a vector loop could be generated at each site. The direction of epicardial impulse propagation as determined by multipoint isochronal activation mapping was compared with that indicated by maximum x,y deflection of the vector loop. At 203 sites (141 normal and 62 infarcted) there was a median error of only 13 degrees and an excellent correlation by linear regression (r2 = .95). In normal myocardium vector lo...
Prevention of nifedipine of abnormal coronary vasoconstriction in patients with coronary artery disease.
Authors: SGunther, LGreen, J EMuller, G HMudge, WGrossman
Journal: Circulation (1981)

The hemodynamic and myocardial metabolic responses to the cold pressor test were studied in 15 patients with coronary artery disease and stable exertional angina. Every patient had abnormal coronary vasoconstriction during a control cold pressor test, even though 14 were receiving propranolol and 12 were receiving long acting nitrates. Mean coronary vascular resistance for the group increased 18 +/- 6% (SD) (from 0.80 +/- 0.12 to 0.94 +/- 0.20 mm Hg/ml/min, p less than 0.05); coronary sinus blood was unchanged, and the arterial-coronary sinus oxygen difference widened significantly (from 11.5 +/- 1.2 to 12.3 +/- 1.2 ml/100 ml, p less than 0.05). Four patients developed angina, accompanied in each instance by a negative arterial-coronary sinus lactate difference. After the administration of nifedipine (10 mg buccally) in 10 patients, the coronary vascular responses to a repeat cold pressor test were normal in each patient. Mean coronary sinus blood flow increased 27 +/- 12% (from 122 +/- 32 to 153 +/- 35 m...
Female Genital Mutilation
Authors: Ronald M. Davis
Journal: JAMA (1995)

Female genital mutilation is the medically unnecessary modification of female genitalia. Female genital mutilation typically occurs at about 7 years of age, but mutilated women suffer severe medical complications throughout their adult lives. Female genital mutilation most frequently occurs in Africa, the Middle East, and Muslim parts of Indonesia and Malaysia, and it is generally part of a ceremonial induction into adult society. Recent political and economic problems in these regions, however, have increased the numbers of students and refugees to the United States. Consequently, US physicians are treating an increasing number of mutilated patients. The Council on Scientific Affairs recommends that US physicians join the World Health Organization, the World Medical Association, and other major health care organizations in opposing all forms of medically unnecessary surgical modification of the female genitalia. (<i>JAMA</i>. 1995;274:1714-1716)
Comparable Quality of Bowel Preparation With Single‐Day Versus Three‐Day Low‐residue Diet: A Randomized Controlled Tria
Authors: S Machlab, E Martínez-Bauer, P López, V Puig-Diví, F Junquera, A Lira, L Hernández, E Brullet, A Selva, P García-Iglesias, J Vives, A Soria, P Pedregal, G Grau, X Calvet, R Campo
Journal: Endoscopy (2021)

Aims There is controversy about the length of low‐residue diet (LRD) for colonoscopy preparation. The aim of the study was to compare one‐day vs. three‐day LRD associated to standard laxative treatment for achieving an adequate colonoscopy preparation in average risk subjects with positive fecal immunochemical test undergoing screening colonoscopy.
8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes.
Authors: A MShah, H ASpurgeon, S JSollott, ATalo, E GLakatta
Journal: Circulation Research (1994)

The role of cGMP in myocardial contraction is not established. Recent reports suggest that nitric oxide, released by endothelial cells or within myocytes, modifies myocardial contraction by raising cGMP. We studied the effects of 8-bromo-cGMP (8bcGMP, 50 mumol/L) on contraction (cell shortening) and simultaneous intracellular Ca2+ transients (indo 1 fluorescence ratio) in intact adult rat ventricular myocytes (0.5 Hz and 25 degrees C) 8bcGMP reduced myocyte twitch amplitude and time to peak shortening (-19.6 +/- 4.2% and -17.6 +/- 1.3%, respectively) and increased steady-state diastolic cell length (+0.6 +/- 0.1 microns, mean +/- SEM, n = 8; all P < .05) but had no effect on shortening velocity, systolic or diastolic fluorescence ratio, or time to peak fluorescence ratio (all P = NS). In 7 of 13 myocytes, this negative inotropic effect was preceded by a transient positive inotropic effect, with small increases in twitch amplitude, shortening velocity, and cytosolic Ca2+ transient. Analysis of 8bcGMP effec...
Nuclear uptake of sex steroid hormones in the cardiovascular system of the baboon.
Authors: H CMcGill, P JSheridan
Journal: Circulation Research (1981)

Cardiac and arterial tissues of six male and six female adult baboons were examined for nuclear uptake of tritiated 5-alpha-dihydrotestosterone (3H-DHT) or tritiated estradiol-17 beta (3H-E2) by autoradiography. 3H-DHT uptake occurred in nuclei of most atrial and ventricular myocardial fibers, no cardiac interstitial tissues, some arterial endothelial cells, most smooth muscle cells of the intima and inner arterial media, and a few smooth muscle cells of the outer arterial media. 3H-E2 uptake occurred in nuclei of a few atrial and ventricular myocardial fibers, many cardiac interstitial cells, occasional arterial endothelial cells, a few smooth muscle cells of the intima and inner arterial media, smooth muscle cells of the outer arterial media, and nearly all adventitial cells. These observations are consistent with other autoradiographic and biochemical findings which indicate that the heart and major arteries of several mammalian species contain androgen and estrogen receptors in distinctive patterns of...
Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates.
Authors: F WSellke, M LArmstrong, D GHarrison
Journal: Circulation (1990)

Atherosclerosis impairs endothelium-dependent relaxation of large conduit arteries. Because coronary resistance vessels are spared from the development of overt atherosclerosis, endothelium-dependent responses were examined in these vascular segments. Malaysian cynomolgus monkeys (n = 6) were made atherosclerotic by being fed a 0.7% cholesterol diet for 18 months. Control monkeys (n = 6) were fed a standard diet. Coronary microvessels (122-220 microns) were studied in a pressurized (20 mm Hg), no-flow state using a video-imaging apparatus. Relaxations of microvessels, preconstricted with the thromboxane analogue U46619, were determined in response to acetylcholine, bradykinin, the calcium ionophore A23187, adenosine, and sodium nitroprusside. Microvascular relaxations to bradykinin and A23187 were reduced in atherosclerotic monkeys compared with controls, whereas acetylcholine produced additional contraction in atherosclerotic monkeys. Responses of preconstricted microvessels to adenosine and sodium nitro...
Functional mitral stenosis in patients with massive mitral annular calcification.
Authors: L EOsterberger, SGoldstein, FKhaja, J BLakier
Journal: Circulation (1981)

Mitral insufficiency with mitral annular calcification occurring predominantly in elderly females has been described. We studied six patients with mitral diastolic obstruction associated with mitral annular calcification without stenosis of the mitral leaflets. Three were males and three were females, aged 43-77 years. All had significant diastolic gradients across the mitral valve (mean gradient 16 mm Hg) recorded at catheterization. Two patients had aortic and three had mitral valve replacement. No patient had retraction of the mitral leaflets, diffuse thickening or fusion of the commissures at surgery or pathologic examination. Three patients had severe mitral insufficiency, one associated with voluminous prolapsing mitral leaflets and one as a result of ruptured chordae tendineae. The left ventricle was dilated in three patients, two with mitral regurgitation and one with mixed aortic valve disease. Active mitral annular motion is a normal event and is necessary for normal valvular function; severe ca...
Echographic assessment of atrial transport, mitral movement, and ventricular performance following electroversion of supraventricular arrhythmias.
Authors: A NDeMaria, J ELies, J FKing, R RMiller, E AAmsterdam, D TMason
Journal: Circulation (1975)

Controversy attends the extent and temporal sequence of improvements in hemodynamic function resulting from the return of atrial contraction following cardioversion of supraventricular arrhythmias. Thus, mitral, left atrial (LA) and left ventricular (LV) echograms were obtained before and one hour after conversion of supraventricular arrhythmias to normal sinus rhythm by direct current countershock in patients with chronic coronary disease or cardiomyopathies without valvular dysfunction. The duration of the rhythm disturbance varied from one day to five years in 22 patients and was indeterminate in 13. Atrial systole immediately produced prominent mitral A waves with anterior valve excursion of 7.5 mm (range 3 to 12) in 33 of the 35 patients (94%). The two patients with atrial electromechanical dissociation reverted to atrial fibrillation within one week. Cardioversion caused a decline in LA diameter (3.5 to 3.2 cm, P less than .001) and a rise in LV end-diastolic dimension (5.2 to 5.5 cm, P less than ...
Abstract 1013: Role of mitochondria and glutamine metabolism in therapy resistance: Combined targeting of estrogen receptor alpha and exportin 1 in endocrine resistant breast cancers
Authors: Eylem Kulkoyluoglu Cotul, Brandi Patrice Smith, Hua Chang, Yosef Landesman, Kevin Duong, Zeynep Madak Erdogan
Journal: Cancer Research (2019)

Abstract Majority of breast cancer specific deaths in women with ERα (+) tumor occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to prevent or delay recurrence of ERα (+) tumors. The objective of this study was to elucidate the role of mitochondrial pathways that are activated in the presence of single therapies and undermine therapy effectiveness in ER (+) breast cancers. In our previous studies, we identified Exportin 1 (XPO1), a nuclear export protein, as an important player in endocrine resistance progression. Selinexor (SXR), an XPO1 antagonist, has been evaluated in multiple later stage clinical trials in patients with relapsed and /or refractory hematological and solid tumor malignancies. Using a combination of transcriptomics, kinase arrays, metabolomics and metabolic flux experiments, we identified glutamine metabolism pathways to be rewired during endocrine resistance. In limited media conditions mimicking nutrient deprived tumor microenvironment, endocrine resistant cells were more dependent on mitochondria for energy production. Their glucose and fatty acid dependency decreased in the presence of SXR and cells were more dependent on glutamine. The effect of glutamine was dependent on conversion of the glutamine to glutamate and mitochondrial complex 1 activity. In order to examine metabolites that might result in the observed phenotype we performed GC/MS whole metabolite profiling and identified aminoacid metabolism pathways to be upregulated when cells were treated with SXR. We demonstrated that combined targeting of XPO1 and ERα rewires metabolic pathways and shuts down both glycolytic and mitochondrial pathways that would eventually lead to autophagy. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine-resistant breast tumors is novel, and given the need for better strategies for improving therapy response of relapsed ERα (+) tumors, our findings show great promise for uncovering the role ERα-XPO1 crosstalk plays in reducing cancer recurrences. Citation Format: Eylem Kulkoyluoglu Cotul, Brandi Patrice Smith, Hua Chang, Yosef Landesman, Kevin Duong, Zeynep Madak Erdogan. Role of mitochondria and glutamine metabolism in therapy resistance: Combined targeting of estrogen receptor alpha and exportin 1 in endocrine resistant breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1013.
Clinical course of patients with normal or slightly or moderately abnormal coronary arteriograms: 10-year follow-up of 521 patients.
Authors: W LProudfit, V GBruschke, F MSones
Journal: Circulation (1980)

The clinical course was followed for 10 years in 521 patients whose coronary arteriograms did not show any severe obstruction. Coronary disease had been suspected in all patients before arteriography. Two of 357 patients thought to have normal arteriograms died from coronary disease and two of 101 patients died who had less than 30% estimated narrowing of at least one coronary artery. Ten deaths ascribed to coronary disease occurred in 63 patinets who had 30-50% narrowing of at least one major coronary artery. The difference in death rates between the normal or mildly diseased groups and the group that had moderate narrowing was significant (p < 0.01). Coronary events (death from coronary disease, subsequent myocardial infarction, or arteriographic evidence of progression of coronary obstruction) occurred in 2.1% of those who had normal arteriograms, 13.8% of the group with mild lesions, and 33% of those with moderate degree of coronary arterial narrowing.
Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.
Authors: B DMyers, W MDeen, B MBrenner
Journal: Circulation Research (1975)

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP. Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases ...