Выпуск опубликован на сайте 12.12.2025 г.
Original Articles
Purpose of the study. To assess the quality of life in patients with cervical cancer (CC) and endometrial cancer (EC) after radical treatment and to evaluate the effectiveness of hyaluronic acid (HA)-based volumizing agents in correcting vulvovaginal atrophy (VVA).
Patients and methods. The study included 201 patients with stage I–III CC and stage I–II EC (FIGO, 2018) after surgical (Group 1, 33.3 %), combined (Group 2, 37.3 %), or concurrent radiotherapy/chemoradiotherapy (Group 3, 29.4 %). Corrective therapy consisted of intravaginal and perineal administration of HA-based formulations according to the authors’ technique. Dynamic evaluation included vaginal transudate pH, Vaginal Health Index (VHI), and sexual function (PISQ‑12).
Results. Following radical treatment, all patients demonstrated severe VVA, which was more pronounced in groups receiving radiotherapy either alone or as adjuvant treatment – vaginal pH 6.59 ± 0.6 and 6.43 ± 0.8, respectively, versus 6.05 ± 0.9 after surgery (p = 0.001 and p = 0.01). VHI was 7.7 ± 2.5 and 9.2 ± 3.7, respectively, compared with 11.1 ± 3.7 in the surgical group (p = 0.00001 and p = 0.02). After restorative therapy, improvements were noted as early as 1 month: in Group 1 – pH 5.2 ± 0.8 and VHI 17.3 ± 2.9; in Group 2 – pH 5.5 ± 0.6 and VHI 16.75 ± 3.0; in Group 3 – pH 5.4 ± 0.7 and VHI 16.7 ± 2.6 (all p < 0.00001, intergroup comparisons p > 0.05), with sustained effect over 12 months. Sexual function normalized: PISQ‑12 decreased from 15.9 ± 6.7 to 12.0 ± 5.0 and from 14.7 ± 6.0 to 12.0 ± 4.7 in Groups 1 and 3 at 1 month, while in Group 2 scores declined from 15.8 ± 4.9 to 9.5 ± 3.5 at later follow-ups (all p < 0.00001).
Conclusion. Patients with CC and EC after radical treatment develop vaginal mucosal atrophy, more pronounced after radiotherapy. This condition can be effectively corrected using HA-based formulations.
One of the approaches to overcoming the problem of tumor radioresistance, which significantly limits the effectiveness of radiotherapy, is the combination of different treatment strategies, including the use of anti-angiogenic agents. However, the drawbacks of existing anti-angiogenic drugs (toxicity, high cost) indicate the need to develop new, safer, and more effective agents of this class.
Purpose of the study. To investigate the efficacy of an experimental combined antitumor therapy that integrates radiation exposure with subchronic parenteral administration of compound T1084, which exhibits anti-angiogenic and hypoxia-targeted cytotoxic activity.
Materials and methods. The study examined the bifunctional compound T1084 (1‑isobutanoyl‑2‑isopropylisothiourea dichloroacetate), which has dual inhibitory activity against nitric oxide synthases (NOS) and pyruvate dehydrogenase kinase (PDK). The compound was developed and synthesized at the A. Tsyb Medical Radiological Research Center (Patent RU2699558). Antitumor efficacy was evaluated in a transplanted solid Ehrlich carcinoma (SEC) model in 149 F1(CBA×C57Bl/6j) mice across two independent experiments performed according to a unified protocol. The animals were divided into four groups: control (tumor-bearing animals), local irradiation of the tumor (10 Gy single dose or 20 Gy fractionated), monotherapy with T1084 (70.7 mg/kg, daily intraperitoneal administration), and combined therapy (T1084 plus gamma irradiation). Irradiation was performed using the Rokus-M gamma unit (⁶⁰Co, 1 Gy/min), and dosimetry was carried out according to the standards of the International Atomic Energy Agency (IAEA). Tumor development was assessed morphometrically.
Results. It was demonstrated that subchronic application of T1084 at a safe dose of 70.7 mg/kg (1/4 LD₁₆) significantly enhanced the antitumor efficacy of different radiotherapy regimens without impairing treatment tolerability or inducing toxic effects. In two independent SEC experiments, the combination therapy produced a consistent and statistically significant antitumor effect (TI = 45–50 %), exceeding the efficacy of radiotherapy alone and of T1084 monotherapy. Conclusion. The experimental data obtained support the rationale for using the NOS/PDK inhibitor T1084 in combination with radiotherapy for the treatment of radioresistant solid tumors characterized by high angiogenic activity.
Neoadjuvant chemotherapy with dual anti-HER2 blockade is the standard of care for early HER2‑positive breast cancer (BC), leading to a complete pathological response (pCR) in a significant proportion of patients. However, the response to therapy is heterogeneous, and the identification of accessible clinicopathological predictors of pCR remains a key challenge for treatment personalization and efficacy prediction.
Purpose of the study. To evaluate the efficacy of the TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) neoadjuvant regimen and to identify independent clinicopathological predictors of achieving pCR in patients with stage IIA–IIIA HER2‑positive BC.
Patients and methods. A single-center retrospective study was conducted at the P.A. Hertsen Moscow Oncology Research Institute. The analysis included data from 120 patients with stage IIA–IIIA HER2‑positive BC who received neoadjuvant TCHP therapy between 2022 and 2025. The primary endpoint was the rate of pCR (ypT0/is ypN0). Univariate comparative analysis and multivariate binary logistic regression were used to identify predictors of response. ROC analysis was used to determine the optimal cutoff value for the predictor.
Results. Complete pathological response was achieved in 70 out of 120 patients (58.3 %). In the multivariate analysis, estrogen receptor (ER) expression level was the only independent predictor of pCR. For each one-point increase in the Allred score for ER expression, the odds of achieving pCR decreased by 16.1 % (OR 0.839; 95 % CI 0.753–0.934; p = 0.001). ROC analysis identified an optimal cutoff value for ER expression of ≤ 6 points for predicting pCR (AUC = 0.665; p = 0.001). Conclusion. ER expression level is a key independent predictor of response to neoadjuvant TCHP therapy in patients with HER2‑positive breast cancer. ER expression assessment can be used in clinical practice as an accessible biomarker for patient stratification and for identifying a group with a lower likelihood of achieving pCR who may require alternative or intensified therapeutic regimens.
Purpose of the study was to evaluate the feasibility of intraoperative lymphography with indocyanine green in cholangiocarcinoma and gallbladder cancer.
Patients and methods. The study included 26 patients with biliary cancer, who underwent intraoperative fluorescent lymphography with indocyanine green (ICG lymphography) during the period from April 2023 to January 2025 while planning lymph node (LN) dissection and liver resection. The lymph drainage from the liver and bile ducts was studied at 1, 3, 5, 10, 15, 30 ± 45 minutes from the ICG introduction with the determination of the first three stained LNs – sentinel lymph nodes (SLNs) – followed by subsequent LN dissection with the removal of regional LNs, as well as all stained LNs outside the areas of regional metastases. When technically possible, the planned volume of liver surgery and biliary tract resection was performed.
Results. In two cases (7.7 %) no SLN was detected, in this group there were no metastases in the LNs. In the remaining cases (92.3 %, n = 24), accumulation of ICG in one or more LNs was noted. LN invasion was noted in 12 patients. In this group, when using the first two stained LNs as SLNs, the sensitivity was 91.7 % (n = 11/12). Studying SLN 3 did not affect the sensitivity, but allowed identifying affected LNs outside the areas of regional metastases in two cases (7,7 %).
Conclusion. ICG lymphography is a promising method for determination of the SLNs and lymphatic drainage pathways in biliary cancer. It is advisable to evaluate the effect of LN dissection performed using fluorescence lymphography on long-term outcomes in patients with resectable biliary cancer.
Purpose of the study. To evaluate the roles of the growth factors IGF‑1, TGF-β, and VEGF-A in regulating delayed regenerative mechanisms induced by N-acetylcysteine (NAC) administered prior to local pancreatic irradiation with electrons at a total dose of 30 Gy.
Materials and methods. An experimental study was conducted on 60 male Wistar rats, which were divided into four groups: Group 1 (control, n = 10): rats received an intraperitoneal injection of NaCl solution without local electron irradiation; Group 2 (n = 20): intraperitoneal administration of 0.9 % NaCl solution prior to local electron irradiation in a fractionated mode with a total focal dose (TFD) of 30 Gy; Group 3 (n = 20): intraperitoneal administration of N-AC at a dose of 120 mg/kg prior to local electron irradiation in a fractionated mode with a TFD of 30 Gy; Group 4 (n = 10): intraperitoneal administration of N-AC at a dose of 120 mg/kg without local electron irradiation. Thirty days after irradiation, blood levels of glucose, insulin, and amylase were measured. Histological analysis of pancreatic islet architecture, the degree of perivascular fibrosis (Masson’s trichrome staining), and the expression of IGF‑1, TGF-β, and VEGF-A were assessed by immunohistochemistry through counting positively stained cells.
Results. Irradiation resulted in elevated blood glucose and amylase levels and decreased insulin levels. Signs of radiation-induced pancreatic injury were accompanied by reduced expression of IGF‑1 and VEGF-A in the islets by 39 % and 56 %, respectively, while the proportion of TGF-β-positive cells exceeded the control values by 3.4‑fold. Pre-irradiation administration of NAC partially preserved biochemical parameters within the normal range, suppressed TGF-β expression, and maintained the numbers of IGF‑1- and VEGF-A-positive endocrine cells at levels 2.5 and 3 times higher than those in the irradiation-only group, respectively.
Conclusion. Pre-irradiation administration of NAC exerts a modulatory effect on the expression of growth factors IGF‑1, TGF-β, and VEGF-A in the late period following local electron irradiation of the pancreas, promoting restoration of the organ’s structural integrity and endocrine function. The obtained data suggest that N-AC is a promising agent for the prevention of delayed post-radiation complications, including fibrosis as well as metabolic and secretory insufficiency of the pancreatic islets.
Purpose of the study. To investigate redox-balance parameters in mitochondria of endometrioid adenocarcinoma (EA) cells in oncogynecological patients, as well as in mitochondria of Guerin carcinoma cells with intramural tumor localization in rats.
Materials and methods. The clinical part of the study included patients who underwent surgical treatment for EA (n = 42) and uterine fibroids (n = 14). Among patients with EA, 16 had well-differentiated tumors (G1), 12 had moderately differentiated tumors (G2), and 14 had poorly differentiated tumors (G3). The mean age of patients with EA was 60.8 ± 2.9 years, and with fibroids – 49.4 ± 2.5 years. None of the patients received neoadjuvant therapy. The experimental part of the study included biological material obtained from non-linear white female laboratory rats (n = 15) weighing 250 ± 25 g. Intramural growth of Guerin carcinoma was reproduced in these animals. In mitochondria isolated from EA, fibroid, and intact uterine tissues, concentrations of the following parameters were determined using standard ELISA methods: mitochondrial superoxide dismutase (SOD‑2), DNA and RNA oxidative modification products, malondialdehyde (MDA), diene conjugates (DC), and total protein (biuret method). Statistical analysis was performed using Statistica 10.0.
Results. In women, mitochondria of EA cells in G1 tumors demonstrated a markedly elevated content of MDA and DC – 2.3‑fold and 2.9‑fold higher, respectively, compared with values in mitochondria of intact uterine tissue. In G2 tumors, MDA levels were 3.2‑fold higher and DC levels 2.7‑fold higher than in intact mitochondria. In G3 tumors, the degree of DNA damage increased 1.6‑fold (p < 0.05), while MDA, DC, and SOD‑2 concentrations increased 2.4‑fold, 3.0‑fold, and 3.4‑fold, respectively, compared with intact values. In female rats, mitochondria isolated from tumor tissues with intramural Guerin carcinoma growth displayed changes similar in direction to the clinical results: DNA damage increased 1.6‑fold (p < 0.05), MDA 1.6‑fold (p < 0.05), DC 1.5‑fold (p < 0.05), and SOD‑2 2.4‑fold.
Conclusion. The oxidative stress and mitochondrial dysfunction identified in malignant cells of women indicate a differentiationdependent pathogenetic feature. Additionally, an identical direction of redox-balance alterations was demonstrated in the experimental subcellular model, supporting the translational relevance of the findings.
Review
Secondary lesion of the lymph nodes of the neck is a significant factor in the prognosis and choice of surgical tactics in patients with malignant neoplasms of the head and neck organs. In early cases of the disease, in order to identify latent metastases, a sentinel lymph node (SLN) biopsy can be performed, according to the results of which it is possible to assume the probability of damage to the remaining groups of cervical lymph nodes and conclude that cervical lymph dissection is necessary.
Purpose of the study. Discussion of the achievements of the scientific community regarding the role of sentinel lymph node biopsy in malignant tumors of the head and neck, and analysis of current detection methods.
Materials and methods. The analysis of scientific sources of the Scientific Electronic Library databases is carried out "eLIBRARY.RU" and "National Center for Biotechnology Information" published in the period from 2010 to 2025, demonstrating the main indicators of the clinical informativeness (frequency of detection, diagnostic accuracy, sensitivity, specificity, predictive value of a negative result) of various methods of detecting sentinel lymph nodes in patients with malignant neoplasms of the head and neck.
Results. Several methods are used to identify sentinel lymph nodes, including instrumental, contrast-visual, radioisotopic, fluorescent, and combined techniques, each having specific advantages and limitations. The most common in clinical practice is the radioisotope detection method, which makes it possible to detect the accumulation of a radiopharmaceutical drug both at the preoperative stage and intraoperatively.
Conclusion. To overcome the limitations of individual lymphography methods, new indicators, including hybrid agents, are being actively developed, offering significant prospects for practical medicine and further scientific research.
The epidermal growth factor receptor (EGFR) is a critical signaling molecule that, upon activation, promotes neoplastic transformation and metastasis. The utilization of targeted drugs, specifically EGFR inhibitors, has emerged as a pivotal component in the management of diverse malignant neoplasms. Among them, low-molecular-weight heterocyclic compounds acting as blockers of the EGFR tyrosine kinase domain occupy a key position.
Purpose of the study. Is to conduct analysis of modern literature data devoted to the development and study of the antitumor acttivity of small molecule EGFR inhibitors, with a focus on blockers of the receptor’s intracellular domain.
Materials and methods. A comprehensive literature search was conducted in the PubMed and eLibrary databases. The following keywords were entered into the search engine: "EGFR inhibitors", "small molecular weight kinase inhibitors" (SMKIs), "antitumor effect", "pyrimidine derivatives", "molecular docking", and "molecular modeling". Original research articles, meta-analyses, randomized controlled trials, and systematic reviews published predominantly published within the last five years.
Results. The review presents the main characteristics of small molecule EGFR inhibitors, their mechanisms of action, and classification. The present study explores the underlying causes of resistance to targeted drugs aimed at the internal domain of the receptor, as well as the available strategies for overcoming such drug resistance. The subsequent sections of this text will discuss the development of new EGFR blockers, strategies for increasing their selectivity and efficacy, including through bioinformatic approaches.
Conclusion. Currently, a significant amount of data has been accumulated on the development and use of small molecule heterocyclic EGFR tyrosine kinase inhibitors in the treatment of cancer patients. The main reasons limiting their use in clinical practice are the emergence of resistance due to receptor mutations and toxicity. In this regard, the search for new candidate compounds with a putative antitumor mechanism of action and high affinity to the target remains relevant. Inhibitory activity against the internal domain of EGFR directly depends on the structure of the heterocycle underlying the drug, which must be taken into account when creating new molecules that block this receptor. An important role in this process is played by computer modeling, which allows for a significant reduction in material costs and time. The presented review can be useful for researchers developing domestic targeted drugs aimed at the internal domain of EGFR, as part of import substitution to ensure the technological sovereignty of the Russian Federation.
Clinical Case Reports
Upper limb lymphedema following axillary lymph node dissection for breast cancer is one of the most common postoperative complications, significantly reducing patients’ quality of life. This clinical case demonstrates the effectiveness of lymphovenular anastomosis (LVA) as a method that allows for the correction of pathological processes associated with obstructive lymphedema at the early and intermediate stages of the disease. The importance of preoperative assessment and mapping of lymphatic and venous vessels using ultrasound technologies is emphasized, as it enables optimization of surgical tactics, improves the procedure’s efficiency, and reduces operative time. The article discusses the pathophysiological features of lymphedema, including vascular sclerosis and decreased lymphatic drainage capacity, as well as the advantages of modern instrumental diagnostic methods in planning LVA. Attention is drawn to the necessity of an individualized approach to each patient, based on thorough preoperative evaluation of the vascular network, as well as the importance of ultrasound monitoring in the postoperative period for controlling the condition of lymphedema.
Thus, the decisive role of a comprehensive strategy – including preliminary diagnostics and meticulous surgical planning – ensures the most effective clinical outcomes in the treatment of upper limb lymphedema using the LVA method.

















