The Laboratory of Radiation Pharmacology has previously developed water-­soluble dialkylaminoalkyl esters of indole‑3‑carboxylic acid, which demonstrated high immunomodulatory, antiviral, and antitumor activity. Based on these established properties, we aimed to enhance their antitumor effect by incorporating cytotoxic alkylating bromo- or bis(2‑chloroethyl)amino substituents into their molecular structure. Compounds T1167 and T1089 were successfully synthesized.

Purpose of the study. To investigate the antitumor and antimetastatic properties of bromo-, bis(2‑chloroethyl)amino-substituted derivatives of N-methyl ethyl esters of indole‑3‑carboxylic acid (T1089 and T1167).

Materials and methods. The study was performed on 65 mice with subcutaneously transplanted lymphogenously metastasizing sarcoma S‑37 (9 × 10⁵ cells/mouse). Compounds were administered intraperitoneally: T1089 at 40 mg/kg, T1167 at 30 mg/kg. Antitumor efficacy was assessed by primary tumor growth dynamics, morphometric and histological parameters.

Results. The studied compounds inhibited primary tumor growth of sarcoma S‑37 (TGI for T1089–22,4 %, for T1167–30,5 %), increased dystrophic and necrotic changes in tumors (T1089 – by 36 %, T1167 – by 55 %), reduced mitotic index by 2‑fold, and exhibited antimetastatic activity, decreasing metastatic areas in inguinal lymph nodes (day 10: T1089 – by 76 %, T1167 – by 89 %) and iliac lymph nodes (day 10: T1089 – by 28,7 %, T1167 – by 60,8 %; day 16: T1089 – by 53,3 %, T1167 – by 45,6 %).

Conclusion. Antitumor and antimetastatic activity of compounds T1089 and T1167 was demonstrated in the sarcoma S‑37 model. The obtained data indicate the promise of compounds combining alkylating cytotoxicity with the immunomodulatory potential inherent to this class. Further research will involve preclinical development including safety assessment, expansion of the range of tumor models studied, and detailed investigation of the mechanisms of action.

Purpose of the study. To investigate the effects of different radiotherapeutic modalities on parameters of the urokinase-type plasminogen activation system of fibrinolysis in the blood of patients with metastatic brain tumors (MBT).

Patients and methods. According to treatment modality, 38 patients with MBT were divided into three groups: the control group received stereotactic radiotherapy to the bed of the resected metastasis with a single focal dose (SFD) of 6 Gy to a total dose of 30 Gy; the comparison group underwent a session of preoperative radiosurgery with an SFD of 10–15 Gy followed by surgical resection of the metastatic lesion 24 h later; the main group received staged radiosurgery (SRS) in three stages with an SFD of 10 Gy and 14‑day intervals between sessions (total dose, 30 Gy). The activity and concentration of urokinase-type plasminogen activator (uPA) and the level of its cellular receptor (uPAR) were measured in blood plasma. The results were compared with those obtained from 18 donors without malignant disease.

Results. Before treatment, patients demonstrated a 3.6‑fold decrease in plasma uPA concentration and a 1.8‑fold decrease in uPAR levels compared with donors (p < 0.0001), which was accompanied by a more than twofold reduction in the activity and concentration of plasminogen activator inhibitor type 1 (PAI‑1). An increase in uPA activity and concentration during treatment was observed only in the SRS group; as a result, one month after treatment, uPA activity was 2.7‑fold higher than in the control group (p < 0.0001), and uPA concentration was 1.2‑fold higher than in the comparison group (p = 0.031), which was accompanied by normalization of uPAR levels.

Normalization of PAI‑1 activity immediately after treatment and one month later was observed only in the main group, while its concentration remained stable. In contrast, the control group exhibited a decrease in PAI‑1 concentration, whereas the comparison group showed an increase in PAI‑1 concentration with a loss of activity on postoperative day 3. In the control group, a pronounced imbalance of the urokinase system was observed, as evidenced by the calculated uPA/uPAR ratios.

Conclusion. The observed differences in the direction of changes in the components of the urokinase system under different radiotherapy modalities are consistent with the superior clinical effectiveness of the developed and patented SRS method in the treatment of patients with MBT.

Purpose of the study. To evaluate the effectiveness of a domestic bioregenerant – the heterogeneous implantable gel composition Sphero®GEL – for the prevention of cervical stenosis following organ-­sparing surgical treatment of cervical intraepithelial neoplasia (CIN).

Patients and methods. The pilot study included 15 patients with cervical intraepithelial neoplasia (CIN) of varying severity after radiosurgical resection of the cervix. On the 14th postoperative day, they received sequential injections into the cervical area of the heterogeneous implantable gel composition Sphero®GEL LIGHT 2.0 No. 1, followed 7 days later by Sphero®GEL MEDIUM 2.0 No. 1. The injections were administered using a bolus technique multifocally across the entire wound surface of the exocervix and multipositionally along the entire circumference and length of the endocervical canal.

Results. Postoperative administration of the injectable heterogeneous implantable Sphero®GEL composition promoted accelerated and effective regeneration with restoration of the cervical anatomical structure after radiosurgical resection. Complete epithelialization was recorded in 13/15 (86.6 %) patients after 1 month, which contributed to the preservation of cervical canal patency and the absence of external os stricture in 15/15 (100.0 %) patients at the 6‑month follow-up. The mean diameter of the cervical canal was 6.33 ± 2.31 mm by Hegar dilator and 6.0 ± 1.0 mm (min. 5, max. 8) by ultrasound cervicometry. The degree of vaginal purity significantly improved from 2.2 ± 0.45 to 1.3 ± 0.46 (p < 0.05) during the course of treatment.

Conclusion. Thus, the use of the domestic bioregenerant and extracellular matrix mimetic – the heterogeneous implantable gel composition Sphero®GEL – in the postoperative period can be considered a promising approach for the prevention of cervical stenosis after organ-­sparing surgical treatment of cervical intraepithelial neoplasia. This provides a basis for the implementation of adequate monitoring and for solving a number of current problems in oncology.

Purpose of the study. To establish the causes of tumor tissue infection in anal cancer with human papillomavirus (HPV), its typical diversity, to determine the relationship between virological response (VR) and complete clinical response (CCR), overall survival (OS) and event-free survival (EFS).

Patients and methods. A total of 41 patients were examined: 36 women (57.1 ± 8.8 years) and 5 men (55 ± 9.5 years) with squamous cell anal cancer; IA–II – 31.7 %, III–IIIA – 24.4 %, IIIB – 43.9 %. The patients underwent conformal radiation therapy to the tumor and lymph collector against the background of chemotherapy (mitomycin, capecitabine). Scrapings from the tumor surface were collected before chemoradiotherapy, upon its completion, after 3 and 6 months. HPV DNA of 14 types was detected by polymerase chain reaction PCR. VR was considered the elimination of HPV in the residual tumor tissue. VR was compared with the indicators of CCR, OS and EFS. Statistical processing was performed using the STATISTICA 10.0 program.

Results. HPV-positive status was confirmed in 34 patients (82.9 %), whereas 7 patients (17.1 %) were HPV-negative. In 73.5 % of HPV+ tumor samples, the virus was in the form of mono-, in 26.5 % – mixed infection. The most frequently detected types of the virus were 16 (82.4 %), 18 (17.6 %) and 31 (8.8 %). Immediately after chemoradiotherapy, HPV+ were 53.8 %, after 3 months – 35.7 %, after 6 months – 34.6 % of patients. Patients with VR achieved CCR in 88.2 % of cases, without VR – 45.5 % (p = 0.0022). In the group with VR, 3‑year EFS was 88.2 %, without VR – 27.3 % (p = 0.00048).

Conclusion. The study demonstrates the clinical potential of HPV DNA detection in residual tumor tissue for assessing the effectiveness of chemoradiotherapy in locally advanced anal cancer. Patients with VR more often achieved PCR and had a higher 3‑year EFS. When assessing the prognosis of chemoradiotherapy effectiveness, it is useful to take into account VR and assess it simultaneously with the assessment of CCR, and to include in the examination plan the analysis of tumor tissue for HPV DNA of a wide range of types during primary diagnostics.

Pancreatoduodenectomy (PD) is characterized by a high rate of complications and mortality. The Failure to Rescue (FTR) metric, defined as mortality following major complications, is recognized as a key indicator of surgical care quality, since inter-­hospital differences in outcomes are determined by the ability to "rescue" the patient rather than by the complication rate.

Purpose of the study. To analyze current scientific data concerning the FTR metric as a marker of care quality in pancreatoduodenectomy.

Materials and methods. A literature search was conducted in the PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library databases for publications from 2000 to 2025 using the following keywords: “failure to rescue,” “pancreatoduodenectomy,” “pancreatic surgery,” “postoperative complications,” “mortality,” and “quality of care.” Eligible publications included original studies (cohort studies, case–control studies, and randomized controlled trials), systematic reviews, and meta-analyses meeting the following criteria: assessment of the failure-to-rescue (FTR) metric in patients undergoing pancreatoduodenectomy; a sample size of at least 100 patients; and a clear definition of postoperative complications and mortality.

Results. The FTR rate ranges from 4 to 41 %, depending on methodology and geographic region. Key risk factors include: age ≥ 65 years, rating on the scale of the American Society of Anesthesiologists (ASA) class ≥ 3, sarcopenic obesity, hypoalbuminemia, renal failure, shock, pancreatic fistula, and accumulation of complications. Systemic factors include low hospital surgical volume, staff shortages, and lack of 24/7 access to interventional radiology. Implementation of the PORSCH algorithm (Postoperative Standardization of Care: the Implementation of Best Practice After Pancreatic Resection) reduced 90‑day mortality from 5 to 3 % (OR 0.42). Centralization of surgery in high-volume centers, ERAS (Enhanced Recovery After Surgery) protocols, and early warning systems EWS (Early Warning Systems) significantly reduce FTR.

Conclusion. FTR is a critical quality indicator in PD. Its reduction is achieved through systemic measures: centralization of care, algorithm-based management, and ensuring access to interventional radiology. Standardization of the FTR is necessary for data comparability.

Epidemiological studies demonstrate the existence of sex differences in cancer incidence and mortality. A substantial body of evidence indicates sex-related differences in responses to anticancer chemotherapy: women experience higher treatment-­related toxicity than men, while at the same time exhibiting better survival, i. e., greater therapeutic efficacy. However, sex differences in oncology remain an underappreciated factor related to tumor biology, treatment efficacy, and patient survival.

Purpose of the study. This review aims to systematically consolidate current evidence on the influence of sex on malignant tumor biology, therapeutic efficacy, and toxicity, and to support the integration of sex as a fundamental variable in oncological research and clinical practice to advance personalized treatment approaches.

Materials and methods. A systematic literature search was conducted in the PubMed, Web of Science, Scopus, and eLibrary.ru databases for publications from 2010 to 2025. Studies were selected based on scientific relevance, topical relevance, and compliance with contemporary standards of evidence-­based medicine.

Results. The analysis identified numerous studies demonstrating significant sex-based differences in cancer epidemiology, the efficacy of anticancer therapy, and the impact of comorbid conditions. The synthesized evidence indicates that sex differences play a fundamental biological role across all aspects of oncology, from molecular mechanisms of carcinogenesis to clinical outcomes. However, despite the accumulated evidence, sex as a biological variable remains insufficiently considered in routine clinical practice.

Conclusion. Consideration of sexual characteristics in oncology would optimize treatment regimens, improve survival rates, reduce therapy side effects, and enhance prognostic models. This would ensure personalized therapy that considers the biological characteristics of men and women.

Purpose of the study. To analyze and synthesize current scientific evidence on the role of CD44 and CK19 expression in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), their diagnostic and prognostic significance, as well as their potential clinical applications and future perspectives.

Materials and methods. The review was based on an analysis of publications from PubMed, Scopus, Web of Science, and Embase using the following keywords: “head and neck squamous cell carcinoma”, “CD44”, “CK19”, “biomarker”, and “prognosis”. The inclusion criteria comprised original studies and meta-analyses; duplicate and irrelevant publications were excluded. Methods for detecting CD44 and CK19, as well as the clinical and demographic characteristics of the studied cohorts, were compared across the included studies.

Results. Increased or aberrant CD44 expression was associated with greater tumor aggressiveness, a higher risk of recurrence and metastasis in HNSCC, while specific isoforms (CD44v4, CD44v6) may indicate therapeutic resistance and an unfavorable disease course. CD44 expression was influenced by several factors, including tumor site, age, and sex. Elevated CK19 levels were associated with poor differentiation, higher malignancy, and an increased risk of recurrence; this marker was frequently detected in HPV-associated tumors. Immunohistochemical and molecular assays for CK19 demonstrated high sensitivity and specificity. Recent studies confirm that the combined assessment of CD44 and CK19 improves the accuracy of risk stratification and clinical monitoring in HNSCC.

Conclusion. CD44 and CK19 are promising biomarkers for a personalized approach to the diagnosis and management of patients with HNSCC. Their combined use improves early risk stratification for disease progression and recurrence, as well as the selection of optimal treatment strategies. Further large-­scale studies and methodological standardization are required to implement these biomarkers in clinical practice to improve patient survival and quality of life.