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Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs).
Front Pharmacol
January 2025
Department of Cardiovascular Center, First Affiliated Hospital of Huzhou University, Huzhou, China.
The emergence of targeted anti-tumor drugs has significantly prolonged the lifespan and improved the prognosis of cancer patients. Among these drugs, vascular endothelial growth factor (VEGF) inhibitors, particularly novel small molecule tyrosine kinase inhibitors (TKIs), are extensively employed as VEGF inhibitors; however, they are also associated with a higher incidence of complications, with hypertension being the most prevalent cardiovascular toxic side effect. Currently, it is widely accepted that TKIs-induced hypertension involves multiple mechanisms including dysregulation of the endothelin (ET) axis, reduced bioavailability of nitric oxide (NO), imbalance in NO-ROS equilibrium system, vascular rarefaction, and activation of epithelial sodium calcium channels; nevertheless, excessive activation of ET system appears to be predominantly responsible for this condition.
View Article and Find Full Text PDFAberrant DNA methylation of EDNRB, MGMT and TIMP3 gene promoters in saliva of head and neck carcinoma patients as a diagnostic tool.
Mol Biol Rep
January 2025
Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
Background: Differential DNA methylation in the promoter region of tumour suppressor genes leads to gene function silencing.
Materials And Methods: In this study, we aimed to evaluate the salivary promoter methylation of EDNRB, MGMT and TIMP3 genes in H&NC patients (n = 100), premalignant lesions patients (n = 25) and healthy controls (n = 50). Blood and saliva samples were collected from all three groups and 20 concomitant tumour tissues were collected from the H&NC patients.
Aprocitentan for Blood Pressure Reduction in Black Patients.
Hypertension
January 2025
John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA (K.C.F.).
Background: Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).
Methods: Patients with confirmed resistant hypertension were randomized to aprocitentan 12.
Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy.
BJC Rep
January 2025
Université Paris-Saclay, CEA, INRAE, Médicaments et Technologies pour la Santé (MTS), SPI, Laboratoire d'Etude de l'Unité Neurovasculaire et Innovation Thérapeutique (LENIT), Gif-sur-Yvette, France.
Background: Endothelin 1 receptors are one of the drivers of tumor progression in many cancers. Inhibition of their signaling pathways with antagonist drugs has been the subject of numerous clinical trials, but the results have not met expectations probably due to the high endothelin concentrations in the tumor microenvironment and their unusually high affinity for their receptors.
Methods: We previously reported the rendomab B49 antibody (RB49) exhibiting a preferential affinity for the activated conformation of human endothelin B receptor (ET), not displaced by high endothelin levels, and without any pharmacological properties that could inhibit the division of melanoma cells.
Repurposing the familiar: Future treatment options against chronic kidney disease.
J Pharm Pharmacol
January 2025
Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, 333031, Rajasthan, India.
Objectives: Chronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that are available against CKD are not uniformly effective and often come with significant side effects.
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