TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies.

Unlabelled: Oncology therapies targeting the immune system have improved patient outcomes across a wide range of tumor types, but resistance due to an inadequate T-cell response in a suppressive tumor microenvironment (TME) remains a significant problem. New therapies that activate an innate immune response and relieve this suppression may be beneficial to overcome this hurdle. TAK-676 is a synthetic novel stimulator of interferon genes (STING) agonist designed for intravenous administration.

Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route.

Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route.

MAP3K11/GDF15 axis is a critical driver of cancer cachexia.

Background: Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome.

Decreased left atrial strain parameters are correlated with prolonged total atrial conduction time in lone atrial fibrillation.

To investigate left atrium (LA) strain properties of patients with lone atrial fibrillation (LAF) and to assess relationships between LA strain parameters and total atrial conduction time measured with tissue Doppler imaging (PA-TDI). The study population consisted of 53 patients with LAF. The control group was comprised of 50 normal volunteers.

A rare case of tricuspid valve thrombus with acute pulmonary embolism.

The development of thrombus on the tricuspid valve is very rare. This report describes a case of acute pulmonary embolism (PE) with a mass on the tricuspid valve in a normal heart, detected by bedside transthoracic echocardiography (TTE). After successful surgical management, the histopathological examination revealed the mass from the tricuspid valve to be mixed thrombus.

Cardiac fibrosis in diabetic rats: regulation and mechanism of activation of the PPARgamma signal pathway.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily which affects organic fibrosis. The aims of the study were to approach the effects of activation of the PPARgamma signal pathway on cardiac fibrosis in diabetic rats, and also the effects on cardiac remodeling and function. Type 1 diabetic models were used in the study.

[Effect of spironolactone on L-arginine/iNOS/NO pathway of aortic adventitia in spontaneously hypertensive rats].

Objective: Adventitia plays an important role in vascular injury diseases. Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is involved in many cardiovascular diseases. iNOS/NO pathway is activated in aorta of spontaneously hypertensive rats (SHRs).

Optimal time for human umbilical cord blood cell transplantation in rats with myocardial infarction.

Background: Cell therapy for cardiac regeneration is still under investigation. To date there have been a limited number of studies describing the optimal time for cell injection. The present study aimed to examine the optimal time for human umbilical cord blood cells (HUCBCs) transplantation after myocardial infarction (MI).

Relationship between integrated backscatter and atrial fibrosis in patients with and without atrial fibrillation who are undergoing coronary bypass surgery.

Objective: The purpose of this study was to investigate the relationship between the integrated backscatter (IBS) and atrial fibrosis, with and without atrial fibrillation (AF), in patients who are undergoing coronary bypass grafting (CABG).

Methods: A total of 74 patients (18 preoperative AF, 56 sinus rhythm [SR]) with coronary artery disease undergoing CABG were included. The IBS of the left atrium (LA) posterior wall was acquired from transthoracic echocardiographic examination before surgery.

Down-regulation of the expression of angiotensin II type 1 receptor in neonatal rat cardiac fibroblast by activation of PPARgamma signal pathway.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is one of the hormone nuclear receptors. Recent data have shown that activation of PPARgamma signal pathway has many positive effects on cardiovascular system. The goals of this study were to determine whether PPARgamma activator affects cardiac fibrosis and the possible mechanisms.

Relation of Hemoglobin A1c to myocardial acoustic densitometry and left ventricular diastolic function in patients with Type 2 diabetes mellitus and without evident heart disease.

Aim: The aim of the study was to detect the echocardiographic sensitive indexes for prediction of the subclinical cardiac dysfunction and to evaluate the relation between Hemoglobin A1c (HbA1c) and myocardial acoustic densitometry as well as cardiac function.

Methods: Fifty DM2 patients (48.5+/-8.

[Effects of carvedilol and metoprolol on cardiac fibrosis in rats with experimental myocardial infarction].

Objective: To investigate the effects of carvedilol and metoprolol on cardiac fibrosis in rats with experimental myocardial infarction (MI).

Methods: MI was induced in male Sprague-Dawley rats by ligating the left coronary artery. Rats randomly received saline, carvedilol (10 mg.

[The effect of radial artery on coronary bypass surgery in patients aged 65 years and older].

Objective: To investigate the effect of autologous radial artery (RA) on coronary artery bypass grafting (CABG) in the elderly aged 65 years and older.

Methods: Three hundreds and twenty-two patients aged 65 years and older underwent CABG with autologous RA from January 2000 to March 2007. Peri-operative complication and mortality were observed and follow-up was performed.

Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent.

Purpose: To prospectively evaluate a gadolinium-based collagen-targeting contrast agent, EP-3533, for in vivo magnetic resonance (MR) imaging of myocardial fibrosis in a mouse model of healed myocardial infarction (MI).

Materials And Methods: All procedures were performed in accordance with protocols approved by the animal care and use committee. MI was induced in eight mice by means of occlusion of the left anterior descending coronary artery followed by reperfusion.

[Efficacy of intravenous aspirin use in patients with acute coronary syndrome].

Objective: To compare the efficacy of intravenous versus oral aspirin use in patients with acute coronary syndrome (ACS).

Methods: ACS patients were randomly treated with intravenous aspirin (300 mg/d, IA, n = 30), low oral aspirin (100 mg/d, OA1, n = 32) or high oral aspirin (300 mg/d, OA2, n = 33). Aspirin sensitivity was tested by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA).

[Effects of aldosterone on inducible nitric oxide synthase/nitric oxide pathway in aortic adventitia].

Objective: To evaluate the effect and related mechanisms of aldosterone (ALD) on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production in aortic adventitia.

Methods: Aortic adventitias from SD rats were incubated for 6 hours with various protocols: buffer alone (control), ALD (10(-8) mol/L - 10(-6) mol/L), ALD + spironolactone (10(-5) mol/L, ALD + SP), ALD + RU486 (10(-5) mol/L), LPS 10 ng/ml (LPS), ALD + LPS (10 ng/ml), ALD + LPS + SP (10(-5) mol/L), and ALD + LPS + RU486. Nitrate/nitrite (NOx), an index of NO production, was measured by Greiss Reaction.

[Protective effects of dexamethasone on myocardium in rats with sepsis].

Objective: To investigate the changes in heart function and myocardial mechanics in murine sepsis model, and the mechanism of the protective effect of dexamethasone on heart.

Methods: Wistar rats were randomly divided into control group, lipopolysaccharide (LPS) group (4 mg/kg LPS intravenously), LPS+dexamethasone group (4 mg/kg LPS+2 mg/kg dexamethasone intravenously), with 32 rats in each group. A catheter was passed through right common carotid artery to the left cardiac ventricle.