Mitochondria regulate a wide range of processes, including stress responses, metabolism, immunity, differentiation, redox homeostasis, and steroidogenesis, and also serve as the principal intracellular source of reactive oxygen species (ROS). Mitochondrial dysfunction has been linked to the development of various pathological conditions, including the growth of both benign and malignant tumors.

Purpose of the study. Determination of the level of steroid hormones in the mitochondria of various tissues of the uterine body.

Materials and methods. The study included 65 patients with benign and malignant diseases of the uterus: 25 patients with endometrioid adeno‑ carcinoma of the uterus (EAC) of low differentiation (G3) stage II–III; 15 patients with leiomyosarcoma of the uterus stage I–III; and 25 patients with uterine myoma. Mitochondria from native samples of uterine tumors were isolated by differential centrifugation in a high-speed refrigerated centrifuge Avanti J-E, Becman Coulter. For the comparison group, mitochondria were isolated from intact uterine tissue. The levels of estradiol (E2), testosterone (T), progesterone (P4), and cortisol were determined using standard ELISA kits (Monobind, USA) in mitochondria isolated from the indicated tissues. A statistical analysis of the results was conducted using the Statistica 10.0 software package.

Results. Irrespective of the nature of the tumor process (benign or malignant), a decrease in the P4 level by 2.7 to 9.1 times, but an increase in the content of cortisol by 1.3 to 3.7 times and T by 2.1 to 3.7 times were detected in the mitochondria of uterine tumors. Conversely, the concentration of E2 in the mitochondria of uterine fibroids exhibited an increase of 2.2 times compared to the indicators in the mitochondria of the intact uterus. No significant differences were observed in the mitochondria of EAC, while a decrease of 1.4 times was noted in the mi‑ tochondria of uterine sarcoma.

Conclusion. There is a change in the content of steroid hormones in In the mitochondria of uterine tumors, consisting in an increase in the concentrations of cortisol and testosterone and progesterone deficiency regardless of the type of pathology, but a relative or absolute defi‑ ciency of estrogens only in the mitochondria of malignant tumors. Changes in the steroid background of tumor mitochondria, compared with the mitochondria of the intact uterus, probably have a significant effect on both the energy balance of cells and the production of ROS, as well as on proliferative processes.

Purpose of the study. To evaluate the antiproliferative properties of the novel alkaloid (P1) against CRC cell lines HT‑29, Caco‑2, and HCT116.

Materials and methods. CRC cell lines (HCT116, HT‑29, Caco‑2) were used in the experiments. The alkaloid (P1) was isolated from Petasites hybridus (L.) G. Gaertn., B. Mey. & Scherb and identified using high-performance liquid chromatography (HPLC) and nuclear magnetic resonance spectroscopy (NMR). Cells were incubated with various concentrations of the alkaloid, and cell viability was assessed. Berberine, a well-known anticancer alkaloid, served as the reference compound.

Results. The alkaloid (P1) demonstrated pronounced antiproliferative activity across all tested colorectal cancer cell lines – HCT116, HT‑29, and Caco‑2. The highest sensitivity was observed in HCT116 cells, with an IC50 value of 15.73 μmol/L after 72‑hour incubation, indicating a substantial inhibitory effect on tumor cell proliferation. Comparative analysis showed that (P1) exhibited greater cytostatic efficacy than berberine in Caco‑2 (IC50 (P1) = 54.489 ± 8.3 μmol/L vs IC50 (berb) = 193.154 ± 13.1 μmol/L) and HT‑29 cultures (IC50 (P1) = 55.375 ± 7.1 μmol/L vs IC50 (berb) = 90.22 ± 8.2 μmol/L).

Conclusion. The findings indicate that the alkaloid (P1) possesses significant antiproliferative potential against colorectal cancer cell lines, underscoring its promise as a prospective anticancer agent. Notably, its superior efficacy compared with berberine highlights the relevance of further investigation. These results support continued development of (P1) as a basis for novel therapeutic agents. Future work should include detailed preclinical and clinical studies to elucidate its mechanism of action, evaluate safety and in vivo efficacy, and optimize pharmacological properties for potential clinical application.

Soft tissue sarcomas (STS) are often resistant to treatment. The search for new antitumor compounds against STS remains an urgent task.

Purpose of the study. To assess the sensitivity of primary STS cultures of various histological subtypes to albendazole sulfoxide (ricobendazole) and doxorubicin, the primary metabolite of albendazole.

Materials and methods. STS tumor samples were used. The enzymatic dissociation method was used using 300 units/ml collagenase I (Thermo Fisher Scientific, USA). Ricasol® (NITA-PHARM, Russia) and Doxorubicin-­LENS® (VEROPHARM, Russia) were used as test substances. Sensitivity to ricobendazole and doxorubicin was tested using the MTT test. The cultures were seeded in a 96‑well plate at 7,000 cells in DMEM medium with 10 % FSC added. After 24 h, the medium was replaced with PPS with ricobendazole in a series of two-fold dilutions from 35.5 μmol/l to 0.0347 μmol/l or doxorubicin from 10 μmol/l to 0.009 μmol/l. After 72 hours of incubation, the MTT test was performed. The cells were seeded in a 24‑well plate and cultured in PPS with 2 μmol/l ricabendazole for 72 h. Hoechst 33342 dye (Life Technologies, USA) was added to the culture at a concentration of 1 μg/ml, and photographs were taken using a LionHeart FX digital automatic microscope (BioTek Instruments Inc., USA).

Results. Four primary sarcoma cultures were obtained: SAR‑1, SAR‑2, SAR‑3, and SAR‑4. SAR-1 and SAR-4. Cultures demonstrated the most rapid growth, with doubling times of 38 and 27 hours, respectively. The slowest proliferation was observed in the SAR-2 culture (doubling time 156 hours), while SAR-3 showed a doubling time of 45 hours. According to the MTT assay, the IC50 values for ricobendazole were 4.54 ± 1.2 μmol/L for SAR-1, 3.31 ± 0.7 μmol/L for SAR-3, and 1.51 ± 0.2 μmol/L for SAR-4, whereas the slowly dividing SAR-2 culture proved to be insensitive to ricobendazole. The cytostatic activity of doxorubicin was higher than that of ricobendazole. The SAR‑2 culture was the least sensitive (IC50 could not be determined), and SAR‑4 (IC50 SAR‑4 = 0.16 ± 0.01 μmol/l) was the most sensitive to the action of doxorubicin. The IC50 value of SAR‑1 = 0.64 ± 0.02 μmol/l and IC50 SAR‑3 = 1.8 ± 0.1 μmol/l. The effect of ricobendazole caused pronounced disturbances in the nuclei of SAR‑1 and SAR‑4 cultures, in SAR‑2 and SAR‑3 they were less pronounced.

Conclusion. Ricobenzale had a cytostatic effect on primary STS cultures characterized by rapid cell growth, but the activity was lower than that of doxorubicin. Changes in the morphology of cells and nuclei indicated probable disturbances in the functioning of the spindle and cytoskeleton occurring under the action of this compound. Of particular interest for further research is the combination of ricobendazole with taxanes and other tubulin inhibitors.

Purpose of the study. To determine the frequency and co-occurrence with major somatic drivers of the germline CHEK2 p.Ile157Thr mutation in patients with non-small cell lung cancer (NSCLC) in the Republic of Tatarstan.

Patients and methods. Targeted next-generation sequencing (NGS) of key oncogenes was performed on tumor tissue from 151 patients. A bibliographic search was carried out manually in Google Scholar and PubMed using the terms “CHEK2 I157T,” “p.Ile157Thr,” “c.470T>C,” “NSCLC,” “germline,” “NGS,” among others; search formulations were refined with the aid of artificial intelligence, followed by mandatory manual verification. Statistical analysis was performed in SPSS v18.0. Proportions were compared using Fisher’s exact test with a significance threshold of p < 0.05.

Results. The p.Ile157Thr variant was identified in 12 patients (7.9 %); all cases (100 %) were histologically confirmed adenocarcinomas. A positive family history of malignant tumors was recorded in 2 patients (16.7 %), and multiple primary malignancies in 2 patients (16.7 %). Concomitant driver mutations were detected in 8 patients (66.7 %): EGFR in 5 (62.5 %), while 3 patients (37.5 %) harbored mutations in KRAS (12.5 %), NRAS, and BRAF, respectively. In 4 patients (33.3 %), p.Ile157Thr was the sole molecular event. In a comparison of carriers versus non-carriers of CHEK2 p.Ile157Thr, no statistically significant differences were observed in stage distribution or in the frequency of co-occurring driver alterations (Fisher’s exact test, p > 0.05).

Conclusion. The germline CHEK2 p.Ile157Thr (c.470T>C) variant was identified in a subset of patients with lung adenocarcinoma and in several cases was accompanied by somatic driver mutations. The obtained data refine the frequency of this variant in the studied population and describe the molecular characteristics of tumors in carriers, providing a basis for further evaluation of the potential clinical relevance of CHEK2 in NSCLC.

Inherited mutations in the BRCA1/BRCA2 genes significantly increase the risk of breast and ovarian cancer in women of reproductive age, posing a clinical and socioeconomic challenge due to loss of fertility during cancer treatment and preventive interventions. The expansion of genetic testing programs is shifting the focus to proactive management of reproductive potential, requiring the integration of oncology, reproductive medicine, and medical genetics. The novelty of this review lies in its comprehensive synthesis of data on the impact of treatment and prevention of BRCA-associated cancer on fertility and a critical assessment of the effectiveness of fertility preservation strategies.

Purpose of the study. To summarize and analyze current advances, clinical guidelines, and unresolved issues related to preserving reproductive function in women carrying BRCA1/BRCA2 mutations.

Materials and methods. A systematic search of PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science was performed, along with an analysis of international guidelines (ESHRE (European Society of Human Reproduction and Embryology), ASCO (American Society of Clinical Oncology), ASRM (American Society for Reproductive Medicine), NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology)). Keywords: “BRCA1,” “BRCA2,” “fertility preservation,” “oocyte cryopreservation,” “embryo cryopreservation,” “ovarian tissue cryopreservation,” “PGT-M,” “PARP inhibitors,” and “chemotherapy gonadotoxicity.”, in the period of 2005–2025. Studies with incomplete data, duplicates, reviews of low methodological quality, and case series with fewer than 10 observations were excluded. Priority was given to meta-analyses, RCTs, large cohorts, and consensus reports.

Results. The included studies included cancer patients before and after treatment, BRCA carriers with and without prophylactic strategies, and IVF/ICSI cohorts with cryopreservation. Alkylating agents and taxanes have been shown to increase the risk of premature ovarian failure, while GnRH agonists partially reduce the risk of ovarian toxicity. The efficacy of oocyte and embryo cryopreservation in BRCA-positive women is comparable to the population-­based efficacy with optimized stimulation (GnRH antagonists, letrozole-­containing protocols). Ovarian tissue cryopreservation is applicable in urgently needed patients but requires oncoprotective assessment. PGT-M ensures the selection of mutation-free embryos. Multidisciplinary pathways improve the timelines of referrals and the completion rate of fertility preservation programs

Conclusion. Early identification of BRCA-positive women and the integration of a gynecologic oncologist, reproductive specialist, and geneticist enable personalized strategy selection: gamete/embryo cryopreservation, ovarian tissue, pharmacoprotection, and PGT-M. Standardized stimulation protocols and therapy timing, long-term safety and fertility data, and economic access models are needed. Improvements in biotechnology and patient pathways improve reproductive outcomes and quality of life.

The development of antitumor strategies aimed at restoring systemic and local immune regulation is considered one of the most promising directions. Technologies based on dendritic cell vaccines (DCVs), characterized by minimal toxicity and alignment with fundamental immunological mechanisms of antitumor resistance, are of particular interest.

Purpose of the study. Is to evaluate the effectiveness of immunotherapeutic approaches for gynecologic malignancies using DCVs and to outline promising directions for further development.

Materials and methods. A literature search was conducted in the bibliographic registers MEDLINE, ClinicalTrial.gov., eLIBRARY and CyberLeninka, using the search systems PubMed, Google Scholar. The vast majority of the identified sources are indexed in Scopus and Web of Science. The review includes more than 60 publications in Russian and English, over 50 % of which were published within the past five years.

Results. The analysis summarizes data on the clinical outcomes of DCV-based therapy in advanced cervical cancer, endometrial cancer, and ovarian cancer. Reported beneficial effects include temporary disease stabilization, improved overall survival and quality of life in advanced malignancies, enhanced efficacy of subsequent chemotherapy, and occasional cases of partial or complete remission. The review also addresses potential reasons for the limited efficacy of DCVs, as well as possible combinations of this technology with other immunotherapeutic modalities and traditional anticancer treatments. The currently modest therapeutic effectiveness of DCVs in gynecologic cancers may be attributed both to the insufficient maturity of the technology and to inherent mechanisms of tumor immune evasion.

Conclusion. The therapeutic potential of DCVs has not yet been fully realized. Advances in immunotherapy, molecular biology, nanotechnology, and strategies for activating systemic and local antitumor resistance mechanisms provide a foundation for defining future research priorities aimed at improving the efficacy of DCVs as an important component of multimodal treatment for gynecologic malignancies.

Epithelioid sarcoma (ES) is an extremely rare disease that, according to morphological data, can be divided into proximal and distal types. The proximal type of ES (PES) of the vulva arises from the superficial and deep layers of the external genital organs, manifests as single or multiple soft tissue tumor nodules with areas of necrosis and hemorrhage, is characterized by aggressive behavior, and has an unfavorable prognosis due to its high tendency for local recurrence and hematogenous metastasis. Differential diagnosis is performed with various benign and malignant neoplasms, cysts or abscesses of the Bartholin gland, and inguinal and femoral hernias. The final diagnosis and histological type of the tumor are established based on morphological, immunohistochemical, and molecular genetic studies. PES is characterized by solid tumor growth composed of large and pleomorphic epithelioid cells with large vesicular nuclei and distinct eosinophilic nucleoli. Immunohistochemically, loss of SMARCB1 (INI1, BAF47) expression is observed, along with positive expression of EMA, vimentin, and cytokeratins; a positive reaction for CD34 staining is often noted in the absence of expression of other endothelial markers such as CD31 and FLI‑1. The clinical presentation and disease characteristics may suggest PES and justify the expansion of the immunohistochemical marker panel. Timely and accurate detection of this tumour plays a key role in improving treatment outcomes, enhancing patients’ quality of life, and reducing mortality. However, due to its rarity, PES of the vulva presents objective diagnostic difficulties in both clinical and morphological aspects. Surgical intervention remains the main method of treatment for this pathology, and to date, there are no clearly established recommendations regarding the optimal management strategy for patients with PES of the vulva. This paper presents a clinical case of a 65‑year-old patient whose atypical clinical presentation of recurrent vulvar tumor served as the basis for expanding the panel of immunohistochemical markers, which allowed for the diagnosis of PES of the vulva.