Chemotherapy In Oncology Research Articles

ONCO-FAIR Project: Improving Data Interoperability in Oncology Chemotherapy Treatments for Data Reuse.

The ONCO-FAIR project's initial experimentation aims to enhance data interoperability in oncology chemotherapy treatments, adhering to the FAIR principles. This study focuses on integrating the HL7 FHIR standard to address interoperability challenges within chemotherapy data exchange. Collaborating with healthcare institutions in Rennes, the research team assessed the limitations of current standards such as PN13, mCODE, and OSIRIS, leading to the customization of twelve FHIR resources complemented by two chemotherapy-specific extensions. The methodological approach follows the Integrating the Healthcare Enterprise (IHE) framework, organizing the process into four key stages to ensure the effectiveness and relevance of health data reuse for research. This framework facilitated the identification of chemotherapy-specific needs, the evaluation of existing standards, and data modeling through a FHIR implementation guide. The article underscores the importance of upstream interoperability for aligning chemotherapy software with clinical data warehouse infrastructure, showcasing the proposed solution's capability to overcome interoperability barriers and promote data reuse in line with FAIR principles. Furthermore, it discusses future directions, including extending this approach to other oncology data categories and enhancing downstream interoperability with health data sharing platforms.

Sonoinduced Tumor Therapy and Metastasis Inhibition by a Ruthenium Complex with Dual Action: Superoxide Anion Sensitization and Ligand Fracture.

Photoresponsive ruthenium(II) complexes have recently emerged as a promising tool for synergistic photodynamic therapy and chemotherapy in oncology, as well as for antimicrobial applications. However, the limited penetration power of photons prevents the treatment of deep-seated lesions. In this study, we introduce a sonoresponsive ruthenium complex capable of generating superoxide anion (O2•-) via type I process and initiating a ligand fracture process upon ultrasound triggering. Attaching hydroxyflavone (HF) as an "electron reservoir" to the octahedral-polypyridyl-ruthenium complex resulted in decreased highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gaps and triplet-state metal to ligand charge transfer (3MLCT) state energy (0.89 eV). This modification enhanced the generation of O2•- under therapeutic ultrasound irradiation at a frequency of 1 MHz. The produced O2•- rapidly induced an intramolecular cascade reaction and HF ligand fracture. As a proof-of-concept, we engineered the Ru complex into a metallopolymer platform (PolyRuHF), which could be activated by low-power ultrasound (1.5 W cm-2, 1.0 MHz, 50% duty cycle) within a centimeter range of tissue. This activation led to O2•- generation and the release of cytotoxic ruthenium complexes. Consequently, PolyRuHF induced cellular apoptosis and ferroptosis by causing mitochondrial dysfunction and excessive toxic lipid peroxidation. Furthermore, PolyRuHF effectively inhibited subcutaneous and orthotopic breast tumors and prevented lung metastasis by downregulating metastasis-related proteins in mice. This study introduces the first sonoresponsive ruthenium complex for sonodynamic therapy/sonoactivated chemotherapy, offering new avenues for deep tumor treatment.

Epidemiology and antimicrobial resistance of toxin-producing Klebsiella oxytoca clinical isolates from children admitted to the oncology chemotherapy center in Mofid Children's Hospital in Tehran, Iran: A cross-sectional study.

Klebsiella oxytoca (K. oxytoca) is the second bacterial cause of nosocomial infections in the general population after K. pneumoniae. This study surveyed the frequency of cytotoxin-producing strains of K. oxytoca and their antibiotic susceptibility profile in a cohort of children admitted to a referral hospital with different malignancies. The Stool samples of children admitted to the Cancer Chemotherapy Unit of the Mofid Children's Hospital, Tehran, Iran were analyzed using conventional biochemical tests and polymerase chain reaction targeting the pehX gene to identify K. oxytoca. The antibiotic susceptibility profile of isolated K. oxytoca against commonly prescribed antibiotics used in treating infection at the facility was determined using the Kirby-Bauer disk diffusion technique. Also, the prevalence of genes encoding toxins among K. oxytoca was identified by PCR assay. The Stool samples of 280 participants were taken for the study of which 38 samples [(55.3% (21/38) 42 males and 44.7% (17/38) females)] tested positive for various Klebsiella spp. Out of this, K. oxytoca was identified in 2.5% (7/280) stools using cultures and conventional biochemical tests. Also, the stools of 2.9% (8/280) of the participants tested positive for K. oxytoca using PCR assay. Using PCR, (2/7) of the K. oxytoca isolates tested positive for the npsA and npsB genes and were identified as toxigenic K. oxytoca strains. The prevalence of toxin-producing K. oxytoca strains in stool samples of children diagnosed with cancer in Iran is relatively low. Most of the K. oxytoca isolates were susceptible to tested antibiotics. Globally, active surveillance of toxigenic K. oxytoca strains in patients with different malignancies or immunocompromised patients is recommended in healthcare settings.

Predictive model for totally implanted venous access ports‑related long‑term complications in patients with lung cancer.

Totally implanted venous access ports (TIVAPs), which are typically used in oncological chemotherapy and parenteral nutritional support, are convenient and safe, and thus offer patients a higher quality of life. However, insertion or removal of the device requires a minor surgical operation. Long-term complications (>30 days post insertion), such as catheter migration, catheter-related thrombosis and infection, are major reasons for TIVAP removal and are associated with a number of factors such as body mass index and hemoglobin count. Since management of complications is typically time-consuming and costly, a predictive model of such events may be of great value. Therefore, in the present study, a predictive model for long-term complications following TIVAP implantation in patients with lung cancer was developed. After excluding patients with a large amount of missing data, 902 patients admitted to The First Affiliated Hospital with Nanjing Medical University (Nanjing, China) were ultimately included in the present study. Of the included patients, 28 had complications, indicating an incidence rate of 3.1%. Patients were randomly divided into training and test cohorts (7:3), and three machine learning-based anomaly detection algorithms, namely, the Isolation Forest, one-class Support Vector Machines (one-class SVM) and Local Outlier Factor, were used to construct a model. The performance of the model was initially evaluated by the Matthew's correlation coefficient (MCC), area under curve (AUC) and accuracy. The one-class SVM model demonstrated the highest performance in classifying the risk of complications associated with the use of the intracavitary electrocardiogram method for TIVAP implantation in patients with lung cancer (MCC, 0.078; AUC, 0.62; accuracy, 66.0%). In conclusion, the predictive model developed in the present study may be used to improve the early detection of TIVAP-related complications in patients with lung cancer, which could lead to the conservation of medical resources and the promotion of medical advances.

Stress symptoms occur in patients undergoing chemotherapy treatment independently of the level of physical activity.

The cancer patient is undergoing a set of procedures that affect the physical and psychological balance, which can generate stressful situations in the organism. In turn, physical activity helps to treat stress, promoting well-being and reducing anxiety. Our study aimed to verify the influence of physical activity practice on stress symptoms in patients undergoing oncological chemotherapy treatment. For this, we used Lipp's Inventory of Stress Symptoms (ISSL) and the International Physical Activity Questionnaire (IPAQ) in 56 patients with cancer. Our data show that 45.4% of the participants exhibited stress scores, of which, 21.8% were at near to exhaustion, and 23.6% at exhaustion. We observed that 30% of them are considered sufficiently active, 25% insufficiently active, 45% sedentary. No association was observed between physical activity and stress. These findings indicate that stress symptoms occur in patients undergoing chemotherapy treatment regardless of the level of physical activity.

Identification and Functional Characterization of PI3K/Akt/mTOR Pathway-Related lncRNAs in Lung Adenocarcinoma: A Retrospective Study.

This paper aimed to investigate the PI3K/Akt/mTOR signal-pathway regulator factor-related lncRNA signatures (PAM-SRFLncSigs), associated with regulators of the indicated signaling pathway in patients with lung adenocarcinoma (LUAD) undergoing immunotherapy. In this retrospective study, we employed univariate Cox, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses to identify prognostically relevant long non-coding RNAs (lncRNAs), construct prognostic models, and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Subsequently, immunoassay and chemotherapy drug screening were conducted. Finally, the prognostic model was validated using the Imvigor210 cohort, and tumor stem cells were analyzed. We identified seven prognosis-related lncRNAs (AC084757.3, AC010999.2, LINC02802, AC026979.2, AC024896.1, LINC00941 and LINC01312). We also developed prognostic models to predict survival in patients with LUAD. KEGG enrichment analysis confirmed association of LUAD with the PI3K/Akt/mTOR signaling pathway. In the analysis of immune function pathways, we discovered three good prognostic pathways (Cytolytic_activity, Inflammation-promoting, T_cell_co-inhibition) in LUAD. Additionally, we screened 73 oncology chemotherapy drugs using the "pRRophetic" algorithm. Identification of seven lncRNAs linked to regulators of the PI3K/Akt/mTOR signaling pathway provided valuable insights into predicting the prognosis of LUAD, understanding the immune microenvironment and optimizing immunotherapy strategies.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy

PurposeNeutropenia, defined as a number of neutrophils in patients’ blood specimen lower than 1500 cells/μm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60–89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN.MethodsThe study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration.ResultsSixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45–27.29; p < 0.01).ConclusionsOur observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

The Application of Nano-drug Delivery System With Sequential Drug Release Strategies in Cancer Therapy.

Currently, multidrug combinations are often used clinically to improve the efficacy of oncology chemotherapy, but multidrug combinations often lead to multidrug resistance and decreased performance, resulting in more severe side effects than monotherapy. Therefore, sequential drug release strategies in time and space as well as nano-carriers that respond to the tumor microenvironment have been developed. First, the advantage of the sequential release strategy is that they can load multiple drugs simultaneously to meet their spatiotemporal requirements and stability, thus exerting synergistic effects of two or more drugs. Second, in some cases, sequential drug delivery of different molecular targets can improve the sensitivity of cancer cells to drugs. Control the metabolism of cancer cells, and remodel tumor vasculature. Finally, some drug combinations with built-in release control are used for sequential administration. This paper focuses on the use of nanotechnology and built-in control device to construct drug delivery carriers with different stimulation responses, thus achieving the sequential release of drugs. Therefore, the nano-sequential delivery carrier provides a new idea and platform for the therapeutic effect of various drugs and the synergistic effect among drugs.

Retracted: Meta-Analysis of the Effect of Dietary Care on Nausea and Vomiting in Oncology Chemotherapy Patients.

[This retracts the article DOI: 10.1155/2022/3163230.].

Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death

Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors of cell metabolism have been studied as potential candidates for chemotherapy in oncology. Mebendazole (MBZ), an antihelminthic approved by FDA, has shown antitumoral activity against cancer cell lines. However, its potential in the modulation of tumoral metabolism remains unclear. Results evidenced that the antitumoral and cytotoxic mechanism of MBZ in GC cells is related to the modulation of the mRNA expression of glycolic targets SLC2A1, HK1, GAPDH, and LDHA. Moreover, in silico analysis has shown that these genes are overexpressed in GC samples, and this increase in expression is related to decreased overall survival rates. Molecular docking revealed that MBZ modifies the protein structure of these targets, which may lead to changes in their protein function. In vitro studies also showed that MBZ induces alterations in glucose uptake, LDH's enzymatic activity, and ATP production. Furthermore, MBZ induced morphologic and intracellular alterations typical of the apoptotic cell death pathway. Thus, this data indicated that the cytotoxic mechanism of MBZ is related to an initial modulation of the tumoral metabolism in the GC cell line. Altogether, our results provide more evidence about the antitumoral mechanism of action of MBZ towards GC cells and reveal metabolic reprogramming as a potential area in the discovery of new pharmacological targets for GC chemotherapy.

The application of nanodrug delivery system with sequential drug release strategies in cancer therapy.

Currently, multidrug combinations are often used clinically to improve the efficacy of oncology chemotherapy, but multidrug combinations often lead to multidrug resistance and decreased performance, resulting in more severe side effects than monotherapy. Therefore, sequential drug release strategies in time and space as well as nanocarriers that respond to the tumor microenvironment have been developed. First, the advantage of the sequential release strategy is that it can load multiple drugs simultaneously to meet their spatiotemporal requirements and stability, thus exerting synergistic effects of two or more drugs. Second, in some cases, sequential drug delivery of different molecular targets can improve the sensitivity of cancer cells to drugs, control the metabolism of cancer cells, and remodel tumor vasculature. Finally, some drug combinations with built-in release control are used for sequential administration. This paper focuses on the use of nanotechnology and built-in control device to construct drug delivery carriers with different stimulation responses, thus achieving the sequential release of drugs. Therefore, the nano-sequential delivery carrier provides a new idea and platform for the therapeutic effect of various drugs and the synergistic effect among the drugs.

The analysis of immunogenic cell death induced by ablation at different temperatures in hepatocellular carcinoma cells.

Introduction: Ablation therapy is a commonly used tool in the management of hepatocellular carcinoma (HCC). After ablation, dying cancer cells release a variety of substances that trigger subsequent immune responses. Immunogenic cell death (ICD) has been a trending topic in recent years and has been discussed many times along with oncologic chemotherapy. However, the subject of ablative therapy and ICDs has been little discussed. The purpose of this study was to investigate whether ablation treatment induces ICD in HCC cells and whether different types of ICDs arise because of different ablation temperatures. Methods: Four different HCC cell lines (H22, Hepa-16, HepG2 and SMMC7221) were cultured and treated under different temperatures (-80°C, -40°C, 0°C, 37°C, and 60°C). Cell Counting Kit-8 assay was performed to analyze the viability of different cell lines. Apoptosis was detected by flow cytometry assay, and a few ICD-related cytokines (calreticulin, ATP, high mobility group box 1, and CXCL10) were detected by immunofluorescence or enzyme-linked immunosorbent assay. Results: The apoptosis rate of all kinds of cells increased significantly in -80°C group (p < 0.01) and 60°C group (p < 0.01). The expression levels of ICD-related cytokines were mostly significantly different between the different groups. For calreticulin, Hepa1-6 cells and SMMC7221 cells showed significantly higher protein expression levels in 60°C group (p < 0.01) and significantly lower protein expression levels -80°C group (p < 0.01). The ATP, high mobility group box 1 and CXCL10 expression levels were significantly higher in 60°C, -80°C and -40°C group of all four cell lines (p < 0.01). Conclusion: Different ablative treatments could induce different types of ICDs in HCC cells, providing a promising track for the development of individualized cancer therapies.

Immature Teratoma: Diagnosis and Management-A Review of the Literature.

An immature teratoma is a germinal malignant tumor composed of three germ cell layers, occurring more frequently in young women. It is the second most frequent among the malignant germinal tumors after dysgerminoma, and it is the only neoplasm with germ cells that are histologically graded. Even if we do not have a consensus regarding its therapeutical management, it has a good prognosis, with an excellent overall survival rate and good fertility preservation. More studies are needed regarding the necessity of adjuvant chemotherapy in pediatric oncology, and because of chemotherapy's long-term adverse effects, surveillance or a targeted treatment is preferred, but the main therapy is fertility-sparing surgery. Special attention should be given to the genetic mapping of the histological pieces for patient risk stratification due to its value in prognosis and future treatment.

Microenvironmentally Responsive Chemotherapeutic Prodrugs and CHEK2 Inhibitors Self-Assembled Micelles: Protecting Fertility and Enhancing Chemotherapy.

Chemotherapy is a widely used and effective adjuvant treatment for cancer, and it has unavoidable damage to female fertility, with statistics showing 38% of women who have received chemotherapy are infertile. How to reduce fertility toxicity while enhancing the oncologic chemotherapy is a clinical challenge. Herein, co-delivery micelles (BML@PMP) are developed, which are composed of a reduction-sensitive paclitaxel prodrug (PMP) for chemotherapy and a CHEK2 inhibitor (BML277) for both fertility protection and chemotherapy enhancement. BML@PMP achieves fertility protection through three actions: (1) Due to the enhanced permeability and retention (EPR) effect, BML@PMP is more enriched in the tumor, while very little in the ovary (about 1/10th of the tumor). (2) Glutathione (GSH) triggers the release of PTX, and with low levels of GSH in the ovary, the amount of PTX released in the ovary is correspondingly reduced. (3) BML277 inhibits oocyte apoptosis by inhibiting the CHEK2-TAp63α pathway. Because of the different downstream targets of CHEK2 in tumor cells and oocytes, BML277 also enhances chemotherapeutic efficacy by reducing DNA damage repair which is activated through the CHEK2 pathway. This bidirectional effect of CHEK2 inhibitor-based co-delivery system represents a promising strategy for improving oncology treatment indices and preventing chemotherapy-associated fertility damage.

Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance

Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release.

Potential agents for combined photodynamic and chemotherapy in oncology based on Pt(II) complexes and pyridine-containing natural chlorins

Combined therapy is currently a popular method for increasing the efficiency of antitumor treatment. It involves the use of two different tumor treatment methods, namely, chemotherapy and PDT. Combining a cytotoxic agent and a photosensitizer in a single molecule results in a synergistic antitumor effect that overcomes the multiple drug resistance and reduces the therapeutic drug doses. In this work, pyridine-containing natural chlorins were obtained by introducing a pyridine group into 131-[Formula: see text]-(4-aminobutyl)amide of chlorin [Formula: see text] and its bacteriochlorin analogue, [Formula: see text]-propyloxime-[Formula: see text]-propoxybacteriopurinimide as well as [Formula: see text]-aminobacteriopurinimide methyl ester. Moreover, a terpyridine residue was introduced as an external chelating moiety into [Formula: see text]-hydroxypurpurinimide and [Formula: see text]-aminobacteriopurinimide, and platinum complexes of all the above photosensitizers were obtained. The interactions of the latter with DNA were simulated and the lead compound, the platinum complex of pyridine derivative 131-[Formula: see text]-(4-aminobutyl)amide chlorin [Formula: see text], which may become a potential agent for combined photodynamic and chemotherapy in oncology, was selected. The ability of the compounds obtained to manifest photodynamic and chemocytotoxic effects on tumor cells of various genesis was shown.

Pharmacological Strategies for Overcoming Multidrug Resistance to Chemotherapy.

Actual mechanisms of multidrug resistance (MDR) to chemotherapy in oncology are considered. ABC-transporters such as P-glycoprotein, BCRP protein, and MRP proteins take part in the development of resistance. The review presents the main classes of chemosensitizers, i.e., inhibitors of ABC transporters of the 1st-4th generations. Plant polyphenols, i.e., flavonoids, are commonly referred to as the last (4th) generation of MDR inhibitors. Chemosensitizers of different classes should be chosen with allowance for the patient mutation-expression profile and the receptor status of a particular tumor. The appropriate dosage of the chemosensitizer and the administration schedule can enhance the process of counteracting MDR.

Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies

Metronomic chemotherapy (MC) is the frequent, regular administration of drug doses designed to maintain a low, but active, range of concentrations of chemotherapeutic drugs, during prolonged periods of time without inducing excessive toxicities. To date, more than 400,000 children and adolescents under the age of 20 are diagnosed with cancer, per year, with 80% survival in most high-income countries, but less than 30% in low- and middle-income ones. In this review, we summarized the principal preclinical and clinical studies involving the use of MC in the most common pediatric tumors, with an overview of efficacy, toxicity, pharmacokinetic profile, and biomarkers. The best advantages of MC are low toxicity, oral administration and, thus, the feasibility of a more comfortable, home-based treatment, therefore improving the quality of life of the children themselves and of their parents and caregivers. Moreover, MC could represent a valid method to reduce the economic burden of anticancer therapy in the pediatric setting.

Insight on the Interaction between the Camptothecin Derivative and DNA Oligomer Mimicking the Target of Topo I Inhibitors.

The understanding of the mechanism of Topo I inhibition by organic ligands is a crucial source of information that has led to the design of more effective and safe pharmaceuticals in oncological chemotherapy. The vast number of inhibitors that have been studied in this respect over the last decades have enabled the creation of a concept of an ‘interfacial inhibitor’, thereby describing the machinery of Topo I inhibition. The central module of action of this machinery is the interface of a Topo I/DNA/inhibitor ternary complex. Most of the ‘interfacial inhibitors’ are primarily kinetic inhibitors that form molecular complexes with an “on–off” rate timing; therefore, all of the contacts between the inhibitor and both the enzyme and the DNA are essential to keep the complex stable and reduce the “off rate”. To test this hypothesis, we designed the compound using a C-9-(N-(2′-hydroxyethyl)amino)methyl substituent in an SN38 core, with a view that a flexible substituent may bind inside the nick of a model of the DNA and stabilize the complex, leading to a reduction in the “off rate” of a ligand in a potential ternary complex in vivo. Using docking analysis and molecular dynamics, free energy calculations on the level of the MM-PBSA and MM-GBSA model, here we presented the in silico-calculated structure of a ternary complex involving the studied compound 1. This confirmed our suggestion that compound 1 is situated in a groove of the nicked DNA model in a few conformations. The number of hydrogen bonds between the components of a ternary complex was established, which strengthens the complex and supports our view. The docking analysis and free energy calculations for the receptor structures which were obtained in the MD simulations of the ternary complex 1/DNA/Topo I show that the binding constant is stronger than it was for similar complexes with TPT, CPT, and SN38, which are commonly considered as strong Topo I inhibitors. The binary complex structure 1/DNA was calculated and compared with the experimental results of a complex that was in a solution. The analysis of the cross-peaks in NOESY spectra allowed us to assign the dipolar interactions between the given protons in the calculated structures. A DOSY experiment in the solution confirmed the strong binding of a ligand in a binary complex, having a Ka of 746 mM−1, which was compared with a Ka of 3.78 mM−1 for TPT. The MALDI-ToF MS showed the presence of the biohybrid, thus evidencing the occurrence of DNA alkylation by compound 1. Because of it having a strong molecular complex, alkylation is the most efficient way to reduce the “on–off” timing as it acts as a tool that causes the cog to brake in a working gear, and this is this activity we want to highlight in our contribution. Finally, the Topo I inhibition test showed a lower IC50 of the studied compound than it did for CPT and SN38.

Early and long-term neurological complications of chemotherapy in oncology (literature review)

An analysis of the clinical manifestations of complications caused by the toxic effect of chemotherapeutic drugs used in the treatment of malignant neoplasms was carried out. The variety of clinical symptoms that develop against the background of chemotherapy for malignant neoplasms leads to difficulties in differential diagnosis of a primary neurological disease and the identification of complications during treatment. The severity of these complications depends on a number of factors, including the drug used, its dosage and duration of use, the use of various methods of combination therapy and radiation methods, as well as the presence of comorbid pathology in patients. A clear understanding of the mechanisms of development of neurotoxicity and timely diagnosis of such conditions is a priority task of modern clinical medicine Modern methods of treating patients with malignant neoplasms should be based on a multidisciplinary medical approach, including a set of measures to prevent unwanted toxic effects of treatment, stratify individual mortality risks and develop methods of rehabilitation and medical examination.