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Adverse effect of trastuzumab deruxtecan in solid tumours: A systematic review and meta-analysis.

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) is approved for use in numerous solid tumours. Here we summarize its safety and tolerability pr … disease (ILD) and grade≥ 3 ILD were 13.2 % and 2.3 % respectively, and 2 % had febrile neutropenia. Cardiotoxicity was rare. Treatment- and ILD- related deaths were reported in 5 % and ILD 1.4 %, respectively. Compared to chemotherapy, T-DXd had higher odds of AEs and treatment discontinuation. Higher dose, non-Caucasian ethnicity and cancer sites other than bre …

Virtual Screening, Toxicity Evaluation and Pharmacokinetics of Erythrina Alkaloids as Acetylcholinesterase Inhibitor Candidates from Natural Products.

PURPOSE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options, necessitating the development … ics simulations. The toxicity predictions indicated a low risk of mutagenicity, hepatotoxicity, and cardiotoxicity. Pharmacokinetic assessments indicated good absorption, moderate blood-brain barrier penetration, and favorable metabolic and excretion profiles, supporting its potential as an orally active drug candidate. CONCLUSION: 8-Oxoerythmelanthine (128) ex …

Синергистические механизмы традиционной китайской медицины и протеиновых ингибаторов в многократной терапии миеломы: всеобъемлющий обзор.

Множественная миелома (ММ) — клональная плазменная порча клеток, характеризующаяся инфильтрацией костного мозга, производством моноклонального иммуноглобулина и многосистемным повреждением. Протеозные ингибиторы (ИП), такие, как бортезомиб, карфилзомиб и иксазомиб, значительно улучшили без прогрессии и общее выживание пациентов с ОМ. Однако резистентность к лекарственным препаратам и неблагоприятные последствия, включая периферическую нейропатию и кардиотоксичность, по-прежнему являются основными ограничениями для долгосрочного контроля за заболеваниями. Цель настоящего обзора заключается в вс

Совпадение в аннотации оригинала
BackgroundMultiple myeloma (MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration, monoclonal immunoglobulin prod … al in MM patients. However, drug resistance and adverse effects-including peripheral neuropathy and cardiotoxicity-remain major limitations to long-term disease control.ObjectiveThis review aims to comprehensively evaluate the synergistic mechanisms and therapeutic potential of Traditional Chinese Medicine (TCM) in combination with PIs for the treatment of MM, f …

Druggability Studies of Benzene Sulfonamide Substituted Diarylamide (E3) as a Novel Diuretic.

Background/Objectives: Urea transporters (UTs) play an important role in the urine-concentrating mechanism and have been regarded as a novel … model. Importantly, E3 did not induce acute oral toxicity, subacute oral toxicity, genotoxicity, or cardiotoxicity. Conclusions: Our study confirms that E3 exerts a diuretic effect by specifically inhibiting UTs and has good druggability, which offers potential for E3 to be developed into a new diuretic for the treatment of hyponatremia.

Cancer-Induced Cardiac Dysfunction: Mechanisms, Diagnostics, and Emerging Therapeutics in the Era of Onco-Cardiology.

Cancer-induced cardiac dysfunction has become a major clinical challenge as advances in cancer therapies continue to extend patient survival. Once regarded as a secondary concern, cardiotoxicity is now recognized as a leading contributor to morbidity and mortality among cancer patients and survivors. Its pathophysiology is multifactorial, involving systemic inflammation (e.g., TNF-α, IL-6), oxidative stress driven by reactive oxygen species (ROS), neurohormonal imbalances (e.g., angiotensin II, endothelin-1), and metabolic disturbances. These mechanisms collectively promote cardiomyocyte apopt…

Spatial metabolomics revealed multi-organ toxicity and visualize metabolite changes induced by borneol in zebrafish.

This study focuses on the potential hazards of borneol (BO) to aquatic organisms and human health. BO has antibacterial, anti-inflammatory a … d induce morphological abnormalities (swim-bladder loss, spinal curvature, body-length shortening), cardiotoxicity (decreased heart rate, increased SV-BA distance), hepatotoxicity (reduced liver area index), and neurotoxicity (impaired behavioral ability, and dopamine neuron development deficits), but there was no renal toxicity observed in zebrafish. Additional …

Evaluation of serum tumor markers in assessing the efficacy of TP (Paclitaxel plus Carboplatin) chemotherapy combined with trastuzumab and pertuzumab dual target therapy in HER2-positive breast cancer.

This study aims to evaluate the efficacy of TP (paclitaxel plus carboplatin) chemotherapy combined with trastuzumab and pertuzumab dual-targ … the two groups in terms of liver function abnormalities, hemoglobin reduction, platelet reduction, cardiotoxicity, gastrointestinal symptoms, and joint muscle pain (P > 0.05). Evaluating the efficacy of TP (paclitaxel plus carboplatin) chemotherapy combined with trastuzumab and pertuzumab dual-target therapy for HER2-positive breast cancer using serum tumor mar …

Nonylphenol exposure and cardiovascular toxicity: Mechanistic insights and integrated risk assessment from experimental models.

Nonylphenol (NP), a widespread environmental endocrine-disrupting chemical, has been extensively studied for its reproductive and neurologic … d genes, with abnormal activation of the relaxin signaling pathway potentially mediating NP-induced cardiotoxicity. Further TRAEC-based risk assessment classified NP as a medium-risk compound (score: 6.50), significantly higher than other alkylphenols such as butylphenol (2.43) and octylphenol (2.95), underscoring its heightened environmental and regulatory conc …

Role of antimalarials in lupus nephritis: a narrative review.

Lupus nephritis (LN) is a severe and common kidney complication of patients with systemic lupus erythematosus (SLE). The manifestations of L … Q is safe and well tolerated, although monitoring for ocular toxicities, skin hyperpigmentation and cardiotoxicity is recommended. Nevertheless, some uncertainties persist regarding the nature, quality, and quantity of the evidence on HCQ, its optimal use, long-term safety, and efficacy across different patient populations. Monitoring HCQ blood levels may furthe …

Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifies MMP16 and KCTD15 as risk loci.

BACKGROUND: Anthracyclines are a widely used and effective class of chemotherapy. However, a major limitation for their use is cardiotoxicity, manifesting as systolic dysfunction, congestive heart failure (HF) and arrhythmias. OBJECTIVE: Identify genes and genetic risk variants for doxorubicin-induced arrhythmia. METHODS: We performed genome-wide association studies (GWAS) and meta-analysis across two independent non-overlapping, genetically homogenous datasets from the Molecular Epidemiology Resource (MER, cases N=77, controls, N=1,184) and Tapestry, (cases N=13, controls, N=172). Doxorubic…

Real-world incidence and risk factors of bortezomib-related cardiovascular adverse events in patients with multiple myeloma.

BACKGROUND: Although most studies on the cardiovascular toxicity of proteasome inhibitors have focused on carfilzomib, the risk of cardiotoxicity associated with bortezomib remains controversial. This study aimed to evaluate the incidence and risk factors of cardiovascular adverse events (CVAEs) associated with bortezomib in patients with multiple myeloma in a real-world setting. METHODS: This cross-sectional study included patients who were treated with bortezomib at a tertiary hospital in South Korea. CVAEs, defined as hypertension, arrhythmia, heart failure, myocardial infarction, pulmonar…

Doxorubicin concentrations in bone tumour-relevant tissues after bolus and continuous infusion: a randomized porcine microdialysis study.

PURPOSE: Doxorubicin is a widely used chemotherapeutic drug that can be administered intravenously as both a bolus infusion and a continuous infusion. The latter is believed to lower the risk of cardiotoxicity, which is a critical long-term complication of doxorubicin treatment. The local tissue concentrations of doxorubicin will be reflected in both treatment efficacy and toxicity, but very limited information is available. The aim of this study was to measure the concentration of doxorubicin after continuous and bolus infusion in tissue compartments around a typical location of a bone tumour…

A Closed Circulation Langendorff Heart Perfusion Method for Cardiac Drug Screening.

Cardiovascular diseases represent an economic burden for health systems accounting for substantial morbidity and mortality worldwide. Despite timely and costly efforts in drug development, the cardiovascular safety and efficacy of the drugs are not always fully achieved. These lead to the drugs' withdrawal with adverse cardiac effects from the market or in the late stages of drug development. There is a growing need for a cost-effective drug screening assay to rapidly detect potential acute drug cardiotoxicity. The Langendorff isolated heart perfusion technique, which provides cardiac hemodyna…

NADPH oxidase 2 inhibitor GSK2795039 prevents doxorubicin-induced cardiac atrophy by attenuating cardiac sympathetic nerve terminal abnormalities and myocyte autophagy.

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every …

The role of the natural compound naringenin in AMPK-mitochondria modulation and colorectal cancer inhibition.

BACKGROUND: Although AMP-activated protein kinase (AMPK) has been extensively studied in cellular processes, the understanding of its substr … tion and mitochondrial fusion in CRC. Naringenin combined with 5-fluorouracil significantly reduces cardiotoxicity and liver damage induced by 5-fluorouracil in nude mice bearing subcutaneous CRC tumors, and attenuates colorectal injuries in azoxymethane/DSS dextran sulfate (AOM/DSS)-induced CRC. The combination of these two drugs alters mitochondrial function b …

Deconvoluting and derisking QRS complex widening to improve cardiac safety profile of novel plasmepsin X antimalarials.

Quinoline-related antimalarial drugs have been associated with cardiotoxicity risk, in particular QT prolongation and QRS complex widening. In collaboration with Medicines for Malaria Venture, we discovered novel plasmepsin X (PMX) inhibitors for malaria treatment. The first lead compounds tested in anesthetized guinea pigs (GPs) induced profound QRS widening, although exhibiting weak inhibition of NaV1.5-mediated currents in standard patch clamp assays. To understand the mechanism(s) underlying QRS widening to identify further compounds devoid of such liability, we established a set of in vit…

Stranded heavy fuel oil exposure causes deformities, cardiac dysfunction, and oxidative stress in marine medaka Oryzias melastigma using an oiled-gravel-column system.

Heavy fuel oil (HFO) stranded on the coastline poses a potential threat to the health of marine fish after an oil spill. In this study, an o … nd pericardial edema. Moreover, the treatments (800, 1600, and 3200 µg oil/g gravel) induced severe cardiotoxicity, characterized by significant bradycardia and reduced stroke volume with an overt decrease in cardiac output. Additionally, the antioxidant enzyme activities, including catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) were signi …

Association of pre-existing cardiovascular disease with administration of fluoropyrimidine chemotherapy in patients with gastrointestinal malignancies.

OBJECTIVE: Fluoropyrimidine chemotherapy is a first-line treatment for many gastrointestinal (GI) cancers, however, cardiotoxicity concerns may limit administration in patients with pre-existing cardiovascular disease (CVD). This study investigated the association of pre-existing CVD with use of fluoropyrimidine chemotherapy in tumour-eligible GI cancer patients. METHODS AND ANALYSIS: National cancer registry data from the Virtual Cardio-Oncology Research Initiative from England between 2014 and 2018 was used to identify GI cancer patients eligible to receive fluoropyrimidine chemotherapy. Li…

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm.

BACKGROUND Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. CASE REPORT We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but su…

Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and th … P3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.