Hepatotoxicity of chemotherapeutic agents: current state of the problem

2016 ◽  
Vol 21 (6) ◽  
pp. 325-333
Author(s):  
M. T Vatutin ◽  
E. V Sklyannaya ◽  
Mariam A. El-Khatib ◽  
S. V Starchenko ◽  
M. V Makarova
Keyword(s):  
Kinase Inhibitors ◽  
Antitumor Agents ◽  
Opportunistic Infections ◽  
Alkylating Agents ◽  
Chemotherapeutic Agents ◽  
Protein Kinase Inhibitors ◽  
Drug Induced ◽  
Anthracycline Antibiotics ◽  
Current State ◽  
High Level

This review is devoted to the actual for the present day problem of the hepatotoxicity of chemotherapeutic agents. Liver is the most important organ essential for the maintaining of the body’s internal environment. For the present time there is observed the high level of the morbidity and mortality rate against the background of drug-induced liver lesions due to, in the first instance, the lack ofproper manner for the substitution of the liver function but transplantation. Liver deteriorations due to the administration of antitumor agents have no pathognomonic clinical or histological features that significantly embarrasses the execution of the differential diagnosis with liver disorders against the background of administration of other preparations, either associated with opportunistic infections or the progression of previously acquired pathology of the liver. In the article there is described the toxic influence on the liver of most often used in oncology chemotherapeutic agents - antimetabolites, alkylating agents, platinum compounds, epothilones, taxanes, vinca alkaloids, monoclonal antibodies, anthracycline antibiotics, topoisomerase and protein kinase inhibitors is described in this article. In the review there are summarized results of recent studies of etiology, pathogenesis, clinical features, diagnosis, prevention and treatment of chemotherapy induced hepatotoxicity. The special attention is given to recent discoveries in the area of pathogenesis of chemotherapy induced hepatotoxicity. However many moments remain to be still not studied completely, that offers perspectives for further research in this field.

scholarly journals CARDIOVASCULAR COMPLICATIONS OF ANTICANCER THERAPY: CLINICAL FEATURES, DIAGNOSIS, TREATMENT, PREVENTION (PART II)

2018 ◽  
Vol 23 (1) ◽  
pp. 43-49
Author(s):  
N. T Vatutin ◽  
E. V Sklyannaya ◽  
Mariam A. El-Khatib ◽  
G. G Taradin
Keyword(s):  
Clinical Features ◽  
Kinase Inhibitors ◽  
Alkylating Agents ◽  
Cardiovascular Complications ◽  
Chemotherapeutic Agents ◽  
Left Ventricular ◽  
Protein Kinase Inhibitors ◽  
Anthracycline Antibiotics ◽  
Treatment And Prevention ◽  
The Given

The given review is devoted to the problem of the cardiotoxicity of chemotherapeutic agents. Many of chemotherapeutic agents can cause cardiovascular complications such as left ventricular dysfunction and heart failure development, myocardial ischemia, arterial hypertension, thromboembolism, QT prolongation and arrhythmias. The toxic influence of the most often used chemotherapeutic agents on heart (such as antimetabolites, alkylating agents, platinum compounds, taxanes, vinca alkaloids, monoclonal antibodies, anthracycline antibiotics, topoisomerase and protein kinase inhibitors, immunomodulatory agents and cytokines) has been described. The results of recent studies on etiology, pathogenesis and clinical features of chemotherapy-induced cardiotoxicity were present in the first part of review. The clinical features, diagnosis, treatment and prevention of the cardiotoxicity of chemotherapeutic agents, are described in the second part of the review

scholarly journals CARDIOVASCULAR COMPLICATIONS OF ANTICANCER THERAPY: DEFINITION, ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, CLASSIFICATION (PART I)

2017 ◽  
Vol 22 (6) ◽  
pp. 345-350
Author(s):  
N. T Vatutin ◽  
E. V Sklyannaya ◽  
Mariam A. El-Khatib ◽  
G. G Taradin
Keyword(s):  
Kinase Inhibitors ◽  
Alkylating Agents ◽  
Cardiovascular Complications ◽  
Chemotherapeutic Agents ◽  
Left Ventricular ◽  
Protein Kinase Inhibitors ◽  
Anthracycline Antibiotics ◽  
Oncological Patients ◽  
Clinically Significant ◽  
Myocardial Injuries

The given review is devoted to the problem of the cardiotoxicity of chemotherapeutic agents. Modern cytostatics cause clinically significant manifestations of cardiotoxicity - myocardial injuries, reducing both quality and life expectancy of oncological patients. Many of chemotherapeutic agents can cause cardiovascular complications such as the development of the left ventricular dysfunction and heart failure, myocardial ischemia, arterial hypertension, thromboembolism, QT prolongation and arrhythmias. The toxic influence of the most often used chemotherapeutic agents on heart (antimetabolites, alkylating agents, platinum compounds, taxanes, vinca alkaloids, monoclonal antibodies, anthracycline antibiotics, topoisomerase and protein kinase inhibitors, immunomodulatory agents and cytokines) has been described. The results of recent studies on etiology, epidemiology, classification and pathogenesis are presented in the first part of review. Most attention is paid to recent research in pathogenesis of chemotherapy induced cardiotoxicity. Given the numerous aspects of cardiotoxicity are not completely studied yet, obviously the further researches are needed in this field.

scholarly journals N-Alkylation of Anthracycline Antibiotics by Natural Sesquiterpene Lactones as a Way to Obtain Antitumor Agents with Reduced Side Effects

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 547
Author(s):  
Margarita Neganova ◽  
Alexey Semakov ◽  
Yulia Aleksandrova ◽  
Ekaterina Yandulova ◽  
Sergey Pukhov ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Sesquiterpene Lactones ◽  
Chemotherapeutic Agents ◽  
Human Organism ◽  
Antitumor Antibiotics ◽  
Anthracycline Antibiotics ◽  
Healthy Environment ◽  
Rat Heart Mitochondria ◽  
First Time ◽  
Potential Antitumor

Anthracycline antitumor antibiotics are one of the promising classes of chemotherapeutic agents for cancer treatment. The main deterrent to their use is high toxicity to a healthy environment, including cumulative cardiotoxicity. In our work, bipharmacophore molecules containing in their structure a fragment of the known anthracycline antibiotics daunorubicin and doxorubicin and natural sesquiterpene lactones were obtained for the first time. When studying the biological activity of the synthesized compounds, it was found that with equal and, in some cases, higher cytotoxicity and glycolysis inhibition by anthracycline antibiotics conjugates with sesquiterpene lactones in comparison with doxo- and daunorubicin, a reduced damaging effect on the functioning of rat heart mitochondria was observed. The results obtained allow us to confirm the assumption that the chemical modification of the anthracycline antibiotics molecules doxo- and daunorubicin by natural sesquiterpene lactones can be a promising strategy for creating potential antitumor chemotherapeutic drugs with a pronounced cytotoxic effect on tumor cells and a reduced damaging effect on healthy cells of the human organism.

scholarly journals The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 532
Author(s):  
Patrizia Leone ◽  
Antonio Giovanni Solimando ◽  
Rossella Fasano ◽  
Antonella Argentiero ◽  
Eleonora Malerba ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Chemotherapeutic Agents ◽  
Protein Kinase Inhibitors ◽  
Great Promise ◽  
Chronic Injury

Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials.

scholarly journals Protein kinase inhibitors--potential chemotherapeutic agents.

1995 ◽  
Vol 42 (4) ◽  
pp. 405-418 ◽  
Author(s):  
D Shugar
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Chemotherapeutic Agents ◽  
Protein Kinase Inhibitors ◽  
Donor And Acceptor ◽  
Catalytic Sites ◽  
Competitive Inhibitors ◽  
Preclinical Trials ◽  
Antiviral Chemotherapy

Protein kinase inhibitors, widely exploited for elucidation of the biological functions of kinases, have more recently come under active consideration as potential chemotherapeutic agents for tumour and other diseases. A brief overview is presented of diverse approaches to the design and development of selective protein kinase inhibitors, and related problems such as donor and acceptor specificities, stereochemical aspects, emerging relationships between protein, sugar and nucleoside kinases. In particular, and contrary to popular belief that ATP-competitive inhibitors cannot be selective because of the close homology of the ATP catalytic sites, numerous examples are presented of such inhibitors which are both potent and selective for a given kinase or class of kinases. Some of these are undergoing preclinical trials. Attention is also directed to the role of cellular and viral protein kinases in the life cycle of viruses, and the potential of these enzymes, especially those encoded by, and essential for replication of, a given virus as targets for antiviral chemotherapy.

scholarly journals Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Zhiqiang Ma ◽  
Liqun Xu ◽  
Dong Liu ◽  
Xiaoyan Zhang ◽  
Shouyin Di ◽  
...  
Keyword(s):  
Side Effects ◽  
Alkylating Agents ◽  
Protective Role ◽  
Chemotherapeutic Agents ◽  
Future Research ◽  
Drug Induced ◽  
Protective Actions ◽  
Age Related ◽  
Comprehensive Reference

Persistent senescence seems to exert detrimental effects fostering ageing and age-related disorders, such as cancer. Chemotherapy is one of the most valuable treatments for cancer, but its clinical application is limited due to adverse side effects. Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy. In this review, we first summarize the mitochondrial protective role of melatonin in the context of chemotherapeutic drug-induced toxicity. Thereafter, we tabulate the protective actions of melatonin against ageing and the harmful roles induced by chemotherapy and chemotherapeutic agents, including anthracyclines, alkylating agents, platinum, antimetabolites, mitotic inhibitors, and molecular-targeted agents. Finally, we discuss several novel directions for future research in this area. The information compiled in this review will provide a comprehensive reference for the protective activities of melatonin in the context of chemotherapy drug-induced toxicity and will contribute to the design of future studies and increase the potential of melatonin as a therapeutic agent.

scholarly journals Atrial Fibrillation Associated with Anticancer Drugs

2020 ◽  
Vol 8 (4) ◽  
pp. 178-190
Author(s):  
O. D. Ostroumova ◽  
M. S. Chernyaeva ◽  
A. I. Kochetkov ◽  
D. I. Bakhteeva ◽  
S. N. Ivanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Adverse Reaction ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Anticancer Agents ◽  
Alkylating Agents ◽  
Protein Kinase Inhibitors ◽  
Drug Induced ◽  
Pathophysiological Mechanisms

Atrial fibrillation is a serious adverse reaction associated with the use of anticancer drugs. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, and risk factors of anticancer drug-induced atrial fibrillation, ways of its prevention and treatment. The results of the study showed that the incidence of drug-induced atrial fibrillation varies depending on a specific anticancer drug and ranges from 1 to 86%. It is associated with the use of herbal anticancer agents, alkylating agents, protein kinase inhibitors, monoclonal antibodies, immunosuppressants, antitumor antibiotics, antimetabolites, hormonal anticancer agents, hormone antagonists, etc. Most often, atrial fibrillation develops following the use of such drugs as gemcitabine (in combination with vinorelbine), cisplatin, melphalan, ibrutinib, cetuximab, trastuzumab, alemtuzumab, and doxorubicin. It was demonstrated that the pathophysiological mechanisms underlying the development of atrial fibrillation induced by anticancer drugs include electrophysiological abnormalities, myocardial injury, inflammation, immune response, apoptosis, and oxidative stress. Risk factors for the development of anticancer drug-induced atrial fibrillation are not clearly defined yet and continue to be the subject of research. Prevention of drug-induced atrial fibrillation in cancer patients requires a multidisciplinary approach involving participation of an oncohematologist and a cardiologist. The doctors in charge should also be vigilant regarding potential development of this adverse reaction. 

scholarly journals Cancer therapy-induced hyponatremia: A case-illustrated review

2021 ◽  
Vol 5 (1) ◽  
pp. 70-78
Author(s):  
Karyne Pelletier ◽  
Marko Škrtić ◽  
Abhijat Kitchlu
Keyword(s):  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Alkylating Agents ◽  
Vinca Alkaloid ◽  
Substantial Improvement ◽  
Adverse Outcomes ◽  
Cancer Therapies ◽  
Drug Induced ◽  
Electrolyte Disorder ◽  
Patients With Cancer

Hyponatremia is the most common electrolyte disorder in patients with cancer and is associated with significant morbidity and mortality. Innovation in cancer therapies has led to substantial improvement in cancer outcomes, but also to new therapy-related toxicities, including electrolyte disturbance. Improvement in clinicians understanding of hyponatremia may mitigate adverse outcomes and improve quality of life in cancer patients. In this case-illustrated review, we discuss the mechanisms underlying drug-induced hyponatremia both in “classical” antineoplastic drugs and novel cancer therapies. Via these clinical cases, we describe hyponatremia caused by conventional chemotherapies (e.g. platinum compounds, vinca alkaloid, and alkylating agents) as well as hyponatremia related to tyrosine kinase inhibitors and other targeted therapies. We also focus on checkpoint inhibitors-induced hyponatremia, as these agents are increasingly used for a wide variety of malignancies. Lastly, we summarize therapy-related hyponatremia among recipients of newer treatments for multiple myeloma.

ФОРМИРОВАНИЕ ПРОФЕССИОНАЛЬНОЙ КУЛЬТУРЫ КУРСАНТОВ КАК НЕОБХОДИМОЕ УСЛОВИЕ СТАНОВЛЕНИЯ СОТРУДНИКА УИС

2020 ◽  
Author(s):  
Alexander Votinov
Keyword(s):  
Russian Federation ◽  
Professional Culture ◽  
Professional Activity ◽  
Teaching Staff ◽  
Successful Performance ◽  
Current State ◽  
Professional Self ◽  
The Russian Federation ◽  
Executive System ◽  
High Level

Современное состояние и развитие уголовно-исполнительной системы Российской Федерации диктует необходимость овладения будущими специалистами комплексом определенных знаний, умений и навыков, позволяющих им эффективно решать служебные задачи. Одним из путей повышения профессионального уровня специалистов является формирование и развитие профессиональной культуры. Проведенный в статье анализ понятия «профессиональная культура» позволяет констатировать сложность его содержания, что связано с особенностями профессиональной деятельности сотрудников УИС, многообразием решаемых задач. Автором подробно исследуется процесс формирования профессиональной культуры в вузах ФСИН России, рассматриваются особенности работы в данном направлении профессорско-преподавательского состава, командиров строевых подразделений, сотрудников отделов по работе с личным составом, приводятся возникающие при этом проблемы и предлагаются возможные пути решения. Отмечается, что успешность формирования профессиональной культуры курсантов зависит от их профессионализма, дисциплинированности, инициативности, настойчивости и личного примера сотрудников. В заключение подчеркивается, что высокий уровень профессиональной культуры сотрудника УИС является условием успешной служебной деятельности и целью дальнейшего профессионального самосовершенствования.The current state and development of the criminal Executive system of the Russian Federation dictates the need for future specialists to master a set of certain knowledge, skills and abilities that allow them to solve official tasks effectively. One of the ways to improve the professional level of specialists is the formation and development of professional culture. The analysis of the concept of «professional culture» in the article allows us to state the complexity of its content, which is associated with the peculiarities of professional activity of employees of the UIS, the variety of tasks to be solved. The author studies in detail the process of formation of professional culture in the universities of the Federal penitentiary service of Russia, examines the features of work in this direction of the teaching staff, commanders of combat units, employees of departments for work with personnel, presents the problems arising in this case and suggests possible solutions. It is noted that the success of the formation of professional culture of cadets depends on their professionalism, discipline, initiative, perseverance and personal example. In conclusion, it is emphasized that the high level of professional culture of the employee is a condition of successful performance and the purpose of further professional self-improvement.

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