Glioblastoma is the most common primary malignant tumor of nervous system and one of the most incurable human tumors. The median of overall survival is 16-17 months after comprehensive treatment. Among various difficulties for new therapeutic approaches, we should emphasize the blood-brain barrier complicating delivery of anti-cancer drugs to neoplasm and perifocal area. A promising approach is aptamer molecules as synthetic amino acid analogs capable of interacting and regulating activity of target proteins based on their spatial structural interactions. Aptamers possess high specificity and affinity to various receptors on cell surface and inside its structures if they penetrate cell membrane. In this review, we present various approaches to development of aptamer-based drugs against glioblastoma. Kopylov A.M. et al. synthesized a series of aptamers targeting EGFR and capable for delivery of toxic agents to tumor cells. Important clinical successes include the results of NOX-A12 drug and data on combined drugs based on trastuzumab in patients with metastatic breast cancer. NOX-A12 is an aptamer blocking CXCL-12 gene and reducing resistance to irradiation of glioblastoma cells. Furthermore, very high control of breast cancer brain metastases in HER-2 positive cases was demonstrated for trastuzumab-emtansine and trastuzumab-deruxtecan. The last finding indicates the perspective for aptamer targeting glioblastoma tumor cells in conjugation with emtansine or deruxtecan.

Pilocytic astrocytomas (PA) are benign CNS tumors with high 5- and 10-year survival rates. Data on aggressive course of PA have occurred since the late 20th century. The purpose of this study was to summarize data on patients with aggressive course of PA. We analyzed own patients with conventional PA, PA with aggressive clinical course and literature data on HGAP. Aggressive group is highly heterogeneous without significant differences in anatomical location between groups. Patients with aggressive course and HGAP were older (M=41, 45.5, and 34 years). Overall 5-year survival in patients aggressive PA was 45%, while no deaths were recorded in the group of conventional PAs. Signs of anaplasia according to histological data and Ki-67 index >8 distinguish conventional PA and tumors with aggressive course. Next-generation sequencing and methylation profiling will improve detection of HGAP.

Hypofractionated irradiation of meningiomas is a relevant fractionation regimen that occupies an intermediate position between radiosurgery and standard fractionation. This study analyzed the experience with this regimen in the Radiotherapy Department of the Burdenko National Medical Research Center of Neurosurgery to evaluate the method's efficacy and safety. A retrospective analysis included patients who underwent radiation therapy between 2017 and 2020. The study included 73 patients. The median age was 56, and the male-to-female ratio was 1:5. Nine patients were diagnosed with schwannomatosis (neurofibromatosis type 2), and 12 had multiple meningiomas. A total of 94 meningiomas were treated with hypofractionation in regimens of 3 and 5 fractions. Twenty eight tumors (29.8%) were previously verified as WHO grade 1 (25) and grade 2 (3). The median target volume was 5.6 cm³ (range 0.2 to 28.9 cm³). Data for analysis were available for 60 patients with 80 tumors, which did not differ significantly in baseline characteristics from the entire group. The local 3-year and 5-year control rate for meningiomas was 95%. Local control did not differ between sporadic tumors and those associated with schwannomatosis and multiple meningiomas. Tumor control was not influenced by volume, number of fractions, dose, treatment platform, histological verification status, or tumor location (skull base vs. convexity). Radiation reactions within 12 months after treatment were detected in 5 tumors (6.3%). The presence of pre-existing peritumoral edema significantly increased the risk of radiation reactions to 60%. A reduction in meningioma size was observed in 61.3% of cases. The median tumor volume reduction was 37% (range 8-84%). This study identified 2 cases (2.5%) of radiation-induced pathomorphosis in the form of appearance and prolonged existence/progression of cysts, which is generally an uncharacteristic clinical course for meningiomas. Thus, hypofractionation is an effective and sufficiently safe method of radiation therapy for meningiomas, enabling the more frequent use of shortened radiation treatment courses instead of prolonged standard fractionation regimens. Given the rare recurrence of meningiomas and the low complication rate, larger and longer-term studies are needed to clarify all factors influencing the outcomes of radiation therapy.

Differentiation of high-grade gliomas (WHO grades III and IV) is still a pressing issue despite advances of molecular biology in tumor stratification. Even with a comprehensive approach to differential diagnosis, uncertainty sometimes arises in classifying a glioma into a particular grade. This can complicate prognosis and selection of appropriate treatment.

Aptamers can increase human glioblastoma cell death rate after exposure to radiotherapy. Cell cultures derived from human glioblastomas allow for selection of effective combined therapy.

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that originate in the parasympathetic paraganglia of the head and neck. The diagnosis of these tumors is challenging, and the therapeutic options are limited. The study of HNPGLs is fraught with challenges at every stage. One of the main problems is the absence of HNPGL cell lines in cell repositories, which is associated with the difficulty of their culturing and low division rate. In this regard, neither functional nor preclinical studies are available for this category of tumors. This significantly slows down the study of the molecular mechanisms of HNPGL pathogenesis and the development of effective therapeutic approaches. Here, we investigated the molecular genetic characteristics of the primary HNPGL culture. Using the single-cell RNA sequencing method, expression patterns were analyzed, and cell types were annotated. The results demonstrated that the HNPGL primary culture cells were optimally divided into three clusters and had different degrees of differentiation, expressing neural tissue cell and stem cell markers. Exome sequencing revealed genetic abnormalities in the HNPGL culture, including mutations in the IGSF3, DHH, EXOSC8, SERPINA1, TYR, and NQO1 genes, aneuploidy, as well as multiple chromosomal duplications and deletions. These results enhance our knowledge of the molecular genetic features of successfully cultured HNPGL tumor cells.

Ovarian cancer remains one of the most lethal malignancies with a five-year survival rate around 20% at III-IV stages, which determines the urgent need to develop new therapeutic approaches. Newcastle disease virus (NDV) has demonstrated considerable promise as an oncolytic agent, capable of selectively lysing tumor cells, suppressing the metastatic potential and stimulating anti-tumor immunity. Despite the established therapeutic potential, studies that investigate oncolytic properties of this virus within the context of ovarian cancer remain limited. In this work, we evaluated oncolytic activity of the NDV vaccine strain H in SC-OV-3, TOV-21G and OV-90 ovarian cancer cell lines. Such parameters as ability to support viral replication and cell viability after infection were investigated. As a result, all three lines were permissive to NDV-H infection. Therapeutic efficacy in vivo was assessed using a model of TOV-21G subcutaneous xenografts in BALB/c nude mice. Upon intravenous administration of the virus, a statistically significant reduction in tumor volume was observed compared to the control group. Based on these results, NDV-H strain can be considered as a potential oncolytic agent for the treatment of ovarian cancer.

The epidermal growth factor receptor (EGFR) is among the research subjects of most interest and remains genuinely attractive due to its key role in regulating the main conserved signaling pathways responsible for cell growth, survival, and proliferation. Dysregulation of the signaling pathways leads to cell malignant transformation, tumor progression, and metastasis. Therefore, EGFR is considered as one of the main targets for anticancer drug development. Although several generations of novel anti-EGFR drugs have been successfully developed, acquisition of drug resistance and the mutation status of the downstream effector protein KRAS significantly reduce the tumor response to therapy. The review focuses on the current approaches to anti-EGFR therapy. Drugs designed to block the EGFR-mediated signaling are described, including monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxins. Mechanisms of acquired resistance to anti-EGFR therapy are discussed, and combination treatment strategies are proposed to improve the efficacy of the available drugs. Finally, promising antitumor agents, including ribonucleases (RNases) of various origins, are considered.

Colorectal cancer remains one of the leading causes of cancer-related mortality, highlighting the importance of optimizing approaches for its early diagnosis and therapy. One promising area in this field is the investigation of the role of the gut microbiome in the initiation and progression of colorectal cancer. This review examines three principal hypotheses explaining the contribution of microbiota to carcinogenesis: the "Alpha-bug", the "Keystone pathogen", and the "Driver-Passenger" models. We analyze data on the mechanisms of microbiota-tumor cells interactions, including the induction of inflammation, genotoxicity, and disruption of the intestinal barrier function. Findings are also presented indicating that certain microorganisms previously considered markers of the advanced stages may possess pro-oncogenic properties, thereby refining existing carcinogenesis models. Overall, the data suggest that the microbiota and its dysbiotic alterations can be considered potential targets for colorectal cancer diagnosis and therapy.

The authors describe a non-standard surgical approach to the treatment of tumor with predominant lesion of membranous tracheal wall. Circular resection with wide excision of membranous wall and replacement of tissue deficiency with autopericardial flap are used. This approach significantly reduced tension of anastomotic sutures, ensured smooth postoperative period and relapse-free survival over 7 years in context of combined treatment of adenoid cystic tracheal cancer.

The authors present surgical treatment of a patient with follicular thyroid tumor and parathyroid gland adenoma. Subsequent analysis recognized oncocytic thyroid gland adenoma manifested by clinical and laboratory picture of primary hyperparathyroidism. Multinodular goiter imitating parathyroid gland adenoma when one of the nodes is located behind thyroid lobe and intrathyroid location of parathyroid gland adenoma are factors complicating differential diagnosis. Therefore, this case of thyroid gland adenoma imitating functionally active parathyroid gland adenoma illustrates the need for alertness with respect to combination and mutual imitation of tumors of thyroid and parathyroid glands requiring surgical intervention. In addition, such cases require differential diagnosis between thyroid and parathyroid neoplasms based on all available laboratory and topical methods.

To demonstrate variable anatomy of inferior mesenteric vein and importance of preoperative vascular examination and imaging.

Colon cancer is one of the five most common cancers worldwide, leading to more than 500.000 deaths annually. It is known that the prevalence of colon cancer increases in parallel with increasing age, which is often associated with an increase in the number of concomitant diseases. The latter, both individually and in combination with each other, can have an impact on the safety of performing surgical interventions.

To determine prognostic factors in resectable common bile duct (CBD) cancer and feasibility of adjuvant therapy.

The problem of giant intrathoracic tumors is still relevant. These tumors occupy more than two parts of the mediastinum and penetrated pleural cavities. The same group includes large hemithorax tumors with spread into mediastinum and compression of adjacent anatomical structures. Many authors all over the world published different aspects of this issue (diagnostic, oncologic, surgical and anesthetic). We discuss some questions concerning the choice of surgical access and surgical techniques. In 1982-2024, there were 40 patients with giant intrathoracic tumors (20 teratomas, 12 solitary fibrous tumors, 4 thymomas, 2 sarcomas, 1 neurinoma and 1 chemodectoma). Transthoracic needle core biopsy was performed in 21 patients. Eight patients had previous attempts of tumor resection. Surgical accesses for giant intrathoracic tumor resection were sternotomy in 25 cases, lateral thoracotomy in 7 cases, hemiclamshell in 2 cases and combined access in 6 cases. Postoperative morbidity was 17.5% (7 patients had different complications after surgery). Of these, 3 ones died (mortality rate 7.5%). Thirty-three (82.5%) patients recovered after surgery well.

Papillary cancer comprises 85-90% of malignant thyroid tumors. About 50% of new cases of papillary thyroid cancer (PTC) are malignant tumors up to 1 cm in size. In Europe, their proportion increased from 18% to 40% over 30 years. This is explained by better diagnosis at earlier stages of disease due to higher quality of ultrasound diagnosis. According to the WHO classification, tumor ≤1 cm is defined as papillary thyroid microcarcinoma (PTMC). In the absence of regional or distant metastases, either follow-up or hemithyroidectomy is recommended. However, tumor metastasis to lymph nodes of the neck is quite common that can contribute to recurrence. Modern ultrasonic diagnosis allows effective preclinical detection of lymph node metastases. In this report, we consider the methods of recurrence detection using retrospective preoperative data in patients who underwent hemithyroidectomy and in whom treatment outcomes are known (presence/absence of recurrence).

O improve functional outcomes after surgical treatment of T1-2 gastric cancer.

Breast cancer remains one of the leading causes of cancer mortality among women, and the study of epigenetic mechanisms is an important task of molecular oncology in breast cancer. In this study, we analyzed the expression levels of eight microRNAs (miR-125b-5p, -127-5p, -129-5p, -132-3p, -148a-3p, -193a- 5p, -24-2-5p, and -34b-3p) and methylation of promoter regions of seven microRNA genes in a representative set of 40 and 70 paired samples of tumor and normal breast tissue, respectively, and showed hypermethylation of promoter regions of seven genes and a statistically significant decrease in the expression levels of eight microRNAs in tumors. For three genes (MIR125B-1, MIR129-2, MIR148A), inverse relationships between methylation and expression (rs < -0.5) were revealed, indicating their possible epigenetic regulation. Statistically significant positive correlations of expression levels were revealed for seven pairwise combinations of miRNAs, suggesting their coordinated functioning. Indeed, for the pairs miR-127-5p/miR-125b-5p, miR-148a-3p/miR-125b-5p, miR-148a-3p/miR-132-3p, and miR-34b-3p/miR-193a-5p, common mRNA targets and involvement in biological processes, including pathways associated with epigenetic regulation, proliferation, and metastasis, were revealed. The miRNA-mRNA regulatory network constructed involving DNMTs and EZH2 highlights their potential role in breast cancer progression and demonstrates diagnostic and prognostic significance.

Pancreatic Ductal AdenoCarcinoma (PDAC) is one of the most therapy-resistant tumors. Cultured cells originating from different stages of PDAC development are characterized by different levels of expression of a number of transcription factors. In particular, poorly differentiated high-grade PDAC cells are characterized by increased expression of ZEB1 gene encoding multifunctional transcription factor ZEB1, one of the main regulators of epithelial-mesenchymal transition. By the method of Circular Chromosome Conformation Capture (4C-seq) we studied the spatial organization of chromatin of regulatory region of ZEB1 gene in cultures of highly differentiated PDAC cells (Capan2) with low level of ZEB1 expression and poorly differentiated PDAC MIA PaCa2 cells with a high level of expression of this gene, and compared it with the chromatin organization of KLF5 gene. The number and distribution of contacts of the ZEB1 regulatory region with other chromatin regions are similar in these cell types and differ significantly from the pattern of distribution of contacts characteristic for KLF5 gene studied earlier. In Capan2 cells, the contacts of the regulatory region of the ZEB1 gene are tend to locate in regions with an increased level of H3K27ac modification, whereas in MIA PaCa2 cells these contacts are predominantly located in regions with a decreased level of H3K27ac. Consequently, the probability of contact of distant chromatin regions is primarily determined not by the degree of chromatin openness/activity of this region. To explain the data obtained, we assumed that the main regulator of the ZEB1 gene transcription level in the studied cells is a transcriptional repressor, whereas for the KLF5 gene main regulator is a transcriptional activator. According to a number of properties, one of the possible candidates for the role of this repressor may be the product of the ZNF438 gene. In addition, we have characterized a number of regions in contact with the ZEB1 promoter that are specific for MIA PaCa2 cells and contain potential regulators of this gene activity.

Primary central nervous system lymphoma is a rare type of extranodal non-Hodgkin's lymphoma that occurs primarily in the central nervous system and represented by diffuse B-cell large cell lymphoma. Despite the fact that this tumor has been known for almost 100 years, studying it is difficult due to the rarity and, consequently, the limited number of statistically significant samples for research. This review analyzes the available literature data on the biological features of primary central nervous system lymphomas, pathogenesis and tumor microenvironment. In addition, we analyzed prognostic factors and current treatment strategies. The objective of this review is to determine the prospects for further study of this tumor.