Роль полиморфных вариантов генов цитохромов Р450, а также генов GSTP1 и MDR1 в развитии токсических осложнений при проведении программной противоопухолевой лекарственной терапии у пациентов с классической лимфомой Ходжкина

Clinical oncohematology, Journal Year: 2024, Volume and Issue: 17(2), P. 141 - 153

Published: April 1, 2024

Background. Although considerable progress has been achieved in the treatment of classical Hodgkin lymphoma (cHL), toxic complications program drug chemotherapy remain an issue. Standard cytostatic agents used cHL therapy are metabolized liver by enzymes with Р450 cytochrome and GSTP1 gene-controlled synthesis. At same time, excretion active metabolites antitumor drugs is mediated MDR1 coded P-glycoprotein. Polymorphisms[1] these genes may change processes biotransformation their metabolite excretion. Additionally, they result organo-toxic complications, disablement patients, even death. Aim. To assess role polymorphisms as well organ toxicity dynamics during (CT) patients. Materials & Methods. The study enrolled 122 patients treated first-line regimens (ABVD, BEACOPP) chemotherapy. were aged 18–78 years (median 35 years); there 67 (54.9 %) women 55 (45.1 men. In compliance NCCN CTC (2003) criteria hepatotoxicity practical recommendations for correcting cardiovascular (2021), signs heart damage assessed all patients. PCR was to analyze MDR1, association CT analyzed. Results. Drug-induced on identified 80 % increasing from cycle 1 6 both ABVD BEACOPP. Complications grade 3/4 observed only BEACOPP recipients. Significant (p < 0.05) associations found between hepatotoxic increased cytolytic (AST, ALT) cholestatic (ALP) values polymorphic variants MDR1. reduction left ventricle myocardium contractility associated Т-allele presence genotypes CYP2D6*10 (rs1065852), CYP2C9*2 (rs1799853) A-allele deletion genotype CYP2D6_3 (rs4986774). Conclusion. identification genetic predictors effects at baseline examination can minimize risks chemotherapy-related adverse events allow maintain a satisfactory quality life. [1] Gene polymorphism structural difference alternative gene. Alternative mutations.

Language: Английский

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Potential of primary drug prevention of cardiotoxicity in the context of anticancer therapy

Russian Journal of Cardiology, Journal Year: 2023, Volume and Issue: 27(12), P. 5258 - 5258

Published: Jan. 5, 2023

Aim . To search early signs of cardiotoxicity in patients receiving anticancer therapy and evaluate the effectiveness cardioprotection with an angiotensin-converting enzyme inhibitor, beta-blocker myocardial cytoprotector. Material methods The study included 98 high very risk according to Mayo Clinic scale (USA). Cancer hypertension were offered cardioprotective treatment a fixed-dose combination perindopril bisoprolol, concomitant coronary artery disease additionally trimetazidine. divided into 2 following groups: experimental group (n=50), where prescribed therapy, control (n=48), which consisted who refused or had contraindications cardioprotection. All underwent examination, including collection complaints anamnesis, physical electrocardiography echocardiography assessment left ventricular (LV) global longitudinal strain before chemotherapy 1, 3, 6, 9 12 months after initiation therapy. Results. In group, by end follow-up, atrial volume index LV end-diastolic significantly increased. main these indicators did not change significantly. final visit, ejection fraction decreased comparison initial value first group. After months, there was significant decrease while this indicator remained within normal range. mortality rate higher (15% vs 2% group). cardiotoxic complications occurred 28%, — 78% patients. Conclusion. demonstrated importance cardiac monitoring primary drug prevention A sig nificant deterioration systolic function shown receive its efficiency

Language: Английский

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Cardiovascular complications in patients with cancer: focus on anthracycline-induced cardiotoxicity

CARDIOVASCULAR THERAPY AND PREVENTION, Journal Year: 2021, Volume and Issue: 20(2), P. 2583 - 2583

Published: March 28, 2021

The article describes prevalence and risk factors of cardiovascular in patients with cancer. problems anthracycline-induced cardiotoxicity, the deleterious effects doxorubicin on heart, as well cardioprotective beta-blockers agents acting renin-angiotensin-aldosterone system pathway are discussed. By cardiotoxicity is implied development various adverse events against background drug therapy for cancer patients. Depending severity myocardial damage, there type I (anthracycline-mediated damage irreversible) II (trastuzumab-mediated dysfunction reversible) cardiotoxicity. Anthracycline-induced turn, divided into acute, early-onset chronic late-onset chronic. At same time, main mechanisms anthracycline cytotoxicity relation to healthy cardiomyocytes stimulation intracellular oxidative stress, a decrease reduced glutathione concentration, inhibition cell redox potential, change iron metabolism. discusses detail (age, hypertension, diabetes, asymptomatic left ventricular dysfunction, documented diseases, heart failure, etc.), treatment anthracycline-mediated

Language: Английский

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A first approach to identifying cardiotoxic effects of breast cancer chemotherapeutic treatment in Kazakhstan

Journal of Clinical Medicine of Kazakhstan, Journal Year: 2022, Volume and Issue: 19(1), P. 28 - 35

Published: Feb. 24, 2022

As known, the clinical efficacy of chemotherapy is limited by cardiotoxicity drugs used. The study aimed to clarify cardiotoxic complications from Aktobe Medical Center database for 2018-2019. Material and methods: We performed a register on essential parameters oncological process, used, duration chemotherapy, types complications, outcomes, including survival. Results: found total 305 breast cancer cases. Chemotherapy was completed without in 65.9% patients; treatment interrupted due - 10.5%; 6.2% cardiovascular were identified. two groups patients, EchoCG + -, showed significant difference number detected CV (p<.001) but no survival rate (p .814). patients with documented 28.1 months vs. 34.3 group ones (p.005). those who 34.9 17.6 individuals whose (p<.001). detailed review four cases fatal outcomes. Conclusion: analysis indicates absence systematic approach recording crucial information regarding cardiotoxicity. There lack concordance actions cardiologists oncologists management BC patients. presence lethal outcomes an established cause cardiac death need revise standpoint cardio-oncology. In general, there develop local protocols screening monitoring undergoing radiation therapy.

Language: Английский

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The Use of Electrical Impedance Research Method to Assess the Heart Response to Drug Treatment

2020 Ural Symposium on Biomedical Engineering, Radioelectronics and Information Technology (USBEREIT), Journal Year: 2020, Volume and Issue: 5 3, P. 48 - 50

Published: May 1, 2020

The article discusses the possibility of using multichannel precordial electro-impedance method for studying heart activity phase structure to assess effect various medical therapeutic drugs on in treatment patients with lymphomas. As a result, it was found that after 3-4 days start course, drug has significant human heart. most responsive indicators are durations atria and ventricles pre-ejection periods. But influence chemotherapy some cases can lead an improvement certain parameters structure. considered electrical impedance research be informative tool control treatment. However, at this stage, there is not enough data about changes during course form informed opinion effect.

Language: Английский

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Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes

Biomeditsinskaya Khimiya, Journal Year: 2020, Volume and Issue: 66(5), P. 357 - 371

Published: Jan. 1, 2020

The manifestation of the side cardiotoxic effect anthracycline antibiotics limits their use in treatment malignant processes some patients. review analyzes main causes susceptibility cardiomyocytes to damaging anthracyclines, primarily associated with an increase free radical oxidation. Currently, research is widely carried out find ways reduce cardiotoxicity, particular, cardioprotective agents complex tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown improve function and metabolism cardiovascular system under various pathological impacts, therefore, it proposed them complications chemotherapy. Statins exhibit direct (hypolipidemic) pleiotropic effects due blockade mevalonic acid synthesis downward biochemical cascades that determine properties. point intersection pharmacological activity anthracyclines statins ability both regulate functioning small GTPase from Rho family, this regard opposite. influence on modification membrane dislocation proteins mediates indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. mechanism statin inhibition doxorubicin DNA-topoisomerase complex, which may be important preventing damage during chemotherapy, discussed. At same time, should noted can accompanied by adverse effects: a provocation increased insulin resistance glucose tolerance, often canceled patients impaired carbohydrate metabolism, so further studies are needed here. also data antitumor statins, sensitize tumor cytostatic drug. It has relationship between characterized not only antagonism, but cases synergism. Despite effects, one most promising cardio- vasoprotectors for cardiomyopathy.

Language: Английский

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Ischemic stroke as the first manifestation of anthracycline cardiomyopathy

Bulletin of the Medical Institute REAVIZ (REHABILITATION DOCTOR AND HEALTH), Journal Year: 2022, Volume and Issue: 12(6), P. 127 - 133

Published: Nov. 13, 2022

This article is devoted to the discussion of cardioembolic complications anthracycline cardiomyopathy. The describes a clinical case cardiotoxicity caused by aggressive neoadjuvant chemotherapy in patient with breast cancer and complicated development ischemic stroke.

Language: Английский

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Changes in the level of cardiomarkers in the development of acute myocardial infarction on the background of chemotherapy of a patient with tongue cancer

South Russian Journal of Cancer, Journal Year: 2021, Volume and Issue: 2(3), P. 48 - 54

Published: Sept. 8, 2021

Cancer is one of the leading causes death and disability worldwide. Timely diagnosis introduction new effective treatments, including intensive radiation chemotherapy regimens, have significantly improved survival forecasts in recent years. At same time, use these types treatment increases risk complications, which includes chemotoxic cardiopathies. In this regard, timely detection complications from cardiovascular system patients receiving courses combination with surgical methods important. This paper presents an assessment significance cardiomarkers early acute myocardial infarction that developed during a patient tongue cancer complicated cardiac history. Patient M., 45 years old, was admitted for St. IVA, T4aN1M0, cl. gr. 2. Planned laboratory instrumental studies were performed. Contraindications not identified. A preoperative course performed, against background patient's condition worsened symptoms cardiopathy. second ECG urgently as result increase ST segment III, aVF established, well study concentration cardiomarkers: highly sensitive troponin I, N-terminal propeptide natriuretic hormone, creatine phosphokinase MB, myoglobin, dynamics changes level indicated development coronary syndrome. The complex application diagnostic procedures, determination cardiomarkers, made it possible to diagnose type 1 on chemotherapy. When analyzing entire array clinical data, initiating factor played decisive role case was, our opinion, polychemotherapy paclitaxel carboplatin, cardiotoxicity. Thus, category initial unfavorable background, due common malignant process presence history cardiodisfunction, requires more careful preparation polychemotherapy, cardiotropic therapy mandatory monitoring main cardiomarkers. most significant levels recorded first hours infarction. An association found between I electrocardiogram.

Language: Английский

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Experimental study of the possibility of reducing the cardiotoxic effects of “Mitomycin C” using an immobilized form of “Mitomycin C” and cytoprotector

Человек и его здоровье, Journal Year: 2021, Volume and Issue: 25(1), P. 45 - 53

Published: Dec. 29, 2021

The objective of this work was to investigate in experiments on laboratory rats the possibility reducing cardiotoxicity anticancer drug Mitomycin C by mixing it with Mesogel before injection and using Mexicor® as a cardioprotective agent. Materials methods. To carry out study, 70 male Wistar were used. body weight animals at beginning experimental study ranged from 180 220 grams. Intraperitoneal administration dose 4 mg/kg once start When administered together Mesogel, drugs combined under aseptic conditions intraperitoneal administration, volume 10.7 ml/kg. form intramuscular injections 60 per day for 14 days. Results. After "Mitomycin C" mg / kg, noticeable decrease contractility rat myocardium during exercise tests observed only 14th day. use mixed "Mesogel" had positive effect, but did not completely exclude manifestation cardiotoxic effects C". greatest efficiency demonstrated groups that received mixture cytoprotective "Mexicor®". Conclusion. combination immobilisation "Mexicor®" found eliminate extent.

Language: Английский

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Cardiovascular toxicity induced by chemotherapy and target drugs: mechanisms, diagnostic and preventive approaches

Человек и его здоровье, Journal Year: 2021, Volume and Issue: 24(4), P. 24 - 33

Published: Jan. 1, 2021

The article aims at presenting the review of literature data concerning mechanisms, diagnostic methods, and preventive approaches for cardiovascular toxicity induced by chemotherapy target drugs. is devoted to currently important issue cardiotoxicity with antineoplastic therapy. Modern cytostatic agents cause clinically significant myocardial damage, which definitely impair quality life decrease expec-tancy in oncological patients. Compared traditional chemotherapy, cancer therapy a new strategy inhibits key molecules signal pathways participating carcinogenesis tumor spread. Target characterized lesser unfavorable effects on normal cells considered future chemotherapy. However, sometimes becomes critical patients administered novel agents. Cardiac oncology sphere medicine comes under scrutiny experts despite fact that many mechanisms complications have not been thoroughly studied. current presents state-of-the-art information monitoring problems safety, contemporary view preventing

Language: Английский

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