Aim: to identify new genetic causes of lynch-like syndrome (LLS), a hereditary tumor syndrome characterized by the development of neoplasms with high microsatellite instability (MSI-H) and the absence of mutations in known Lynch syndrome genes.Material and Methods. The study included 18 cases of MSI-H colorectal cancer (CRC), endometrial cancer (EC), and gastric cancer (GC) in young patients without mutations in the MLH1, MSH2 (EPCAM), MSH6, and PMS2 genes. Whole-exome sequencing was performed on DNA from patients’ peripheral blood samples.Results. At least one pathogenic or potentially significant/candidate genetic variant was detected in all cases (77 variants total). Most patients carried a combination of several potentially significant variants. The most significant finding was the identification of a FAN1 gene variant of uncertain significance (VUS) co-occurring with an EXO1 gene mutation in a young patient with MSI-H CRC. Digenic inheritance involving these two functionally related genes had been previously proposed as a hypothetical mechanism for LLS. Another case of presumed digenic inheritance was identified: co-occurrence of two VUS in the TP63 and TP73 genes, both predicted to be functionally significant by bioinformatics tools. A number of VUS and pathogenic/ likely pathogenic (P/LP) variants were found in candidate CRC genes: LRP1 (n=2), HECW1, PSME4, APCDD1, HIC1, CDK18, SMAD6, ZNRF3, WIF1, WNK2, RBBP8NL, MAP1LC3A. Several new candidate CRC genes are proposed: ST6GALNAC1, TGFB1I1, TGFB1, PTPRD, NUDCD2, WIF1, STAG3, NFATC2, HNF4G. Seventeen out of 77 potentially significant variants were heterozygous VUS or P/ LP variants in DNA repair genes: ABRAXAS1 (P/LP), FANCD2, BLM (P/LP), CHEK2 (hypomorphic mutation), RECQL4, BRIP1, ERCC2, ERCC3, XPC (P/LP), MUTYH (P/LP), UNG, REV3L, PARP1, PARP3, LIG1.Conclusion. Whole-exome sequencing enabled the detection of potentially significant genetic variants in the studied patients. Verification of the clinical significance of the candidate genes and variants will be possible as epidemiological data continues to accumulate.
Objective: to summarize the accumulated knowledge on the role of PPM1D phosphatase in clonal hematopoiesis and the pathogenesis of hematological malignancies, particularly in acute myeloid leukemia, as well as to evaluate the feasibility of therapeutic targeting of PPM1D using specific inhibitors.Materials and Methods. a search for relevant sources was conducted in the Web of science, PubMed, and scopus databases. Publications were selected based on the relevance of the studies and the pertinence of their subject matter to the topic of the review, the literature search was performed using the following key terms: “mutations of PPM1D", “PPM1D and cancer”, “clonal hematopoiesis”, “PPM1D and clonal hematopoiesis”, “PPM1D gene”, “WIP1 phosphatase”, “clonal hematopoiesis of indeterminate potential”, “therapy-related AML”, “p53 signaling pathway”, “cell cycle regulation”, “targeted cancer therapy”, “hematologic malignancies”, “truncating mutations” and “inhibitors of PPM1D”. A total of 142 sources were analyzed, of which 63 were included in the review.Results. Clonal hematopoiesis of indeterminate potential (CHIP) is characterized as a condition involving somatic mutations in driver genes of myeloid neoplasms at a variant allele frequency of >2 % in blood cells of individuals without hematological disorders. The prevalence of CHIP exceeds 10 % in individuals over 60 years of age and reaches 25 % in cancer patients. Antineoplastic therapy promotes the selection of hematopoietic stem cell clones harboring mutations, including mutations in the PPM1D gene, which substantially increases the risk of developing therapy-related myeloid neoplasms (t-MN). PPM1D phosphatase is a negative regulator of p53 and numerous cell death pathways. Its overexpression is detected in various types of solid tumors (ovarian cancer, breast cancer, and others), while its mutations are identified in 1-2 % of patients with de novo myeloid neoplasms and in 10-20 % of patients with t-MN. Recent studies demonstrate the predominant role of PPM1D mutations in age-associated clonal hematopoiesis, in the context of telomere shortening, and in the presence of germline DNA repair mutations, thereby underscoring the pivotal significance of this phosphatase in the pathogenesis of myeloid disorders.Conclusion. PPM1D represents a promising therapeutic target for the treatment of AML owing to its key role in the regulation of multiple cell death pathways and the cellular stress response. PPM1D inhibitors may serve as a foundation for the development of combination therapy regimens, particularly for elderly patients and those with acquired resistance to antineoplastic agents.
Introduction. Gastric cancer remains the leading cause of cancer-related morbidity and mortality worldwide and in Russia. In recent years, significant progress in treatment has been made through the use of modern neoadjuvant/perioperative therapy techniques. The grade of tumor pathomorphological response is a direct indicator of the effectiveness of neoadjuvant therapy, but the correlation between this response and long-term treatment outcomes varies significantly among different authors. The impact of a complete morphological tumor response on the patient’s treatment strategy and disease prognosis is a crucial scientific and practical challenge, and it remains a subject of debate.Material and Methods. The study is planned as a multicenter, cohort, non-interventional, retrospective, open clinical trial. The studied treatment approach is neoadjuvant/ perioperative therapy followed by radical surgery for gastric and esophagogastric junction cancer in patients with complete tumor pathomorphological response after neoadjuvant therapy. The study is planned to include 200–250 patients who meet the following main criteria: morphologically verified gastric cancer (adenocarcinoma) and esophagogastric junction (Siewert III); clinical stage I–IVA, M0; neoadjuvant therapy (at least 1 cycle of chemotherapy) and radical surgery; pathomorphological stage of T0N0/N1–3. The primary endpoint (the main goal of the study) is to assess the 3-year overall survival rate. The total duration of the study will be 12 months. To analyze the treatment outcomes, an original database will be created using the Microsoft Excel 2010 program. Statistical analysis will be performed using the SPSS program, version 23.0. The study will be conducted in accordance with the principles of the Declaration of Helsinki, international and Russian rules for conducting scientific research in the field of medicine, and the legislation of the Russian Federation, and it has been approved by the Ethics Committee of the A.F. Tsyb Medical Research Center.Results. For the first time in Russia, a multicenter retrospective clinical study will be conducted to assess the treatment outcomes in patients with locally advanced stomach cancer and esophagogastric junction cancer, provided that the tumor has a complete pathomorphological response after neoadjuvant therapy. The collected data (approximately 250 cases) is expected to be the largest in the world for this category of clinical observations. For the first time, representative data will be obtained based on the treatment outcomes of the Russian population of gastric cancer patients, including in real-world clinical settings.Conclusion. It is expected that the results obtained during the implementation of this study will have both important scientific significance and practical application, including the possibility of using them in the national clinical guidelines.
The purpose of the study was to improve radiotherapy efficacy by optimizing fractionation regimens in patients with inoperable stage llb-lll locally advanced pancreatic cancer.Material and Methods. Treatment outcomes of 60 patients with inoperable stage llb-lll locally advanced pancreatic cancer were analyzed in a single-center comparative study with a retrospective analysis of prospectively collected clinical data. All patients received chemoradiotherapy, including 3 or more cycles of polychemotherapy (PCT) with FOLFlRlNOX or GEMCAP regimen in combination with daily split-dose radiation therapy (RT) (group A) or stereotactic radiotherapy (STRT) (group B).Results. The efficacy of daily split-dose RT was found to be higher than that of stereotactic RT Early radiation reactions corresponded to grade l-ll and were observed in both groups. lncreased levels of transaminases were the most common: in 36.7 % of patients in group A and in 46.7 % in group B (p=0.59). Nausea/vomiting was observed in 23.3 % and 40.0 %, respectively (p=0.18). An analysis of the immediate results showed that the overall rate of objective response was significantly higher in group A compared with group B (93.3 vs 70.0 %; p=0.03). However, disease progression was observed more frequently in group B than in group A patients (30.0 vs 6.7 %; p=0.042). The daily split-course regimen demonstrated significantly higher one-year (73 vs 48 %) and two-year (39 vs 15 %) overall survival rates than stereotactic RT (p<0.05).Conclusion. Our study demonstrated the use of combination therapy in a carefully selected group of patients with inoperable stage llb-lll locally advanced pancreatic cancer. This type of therapy allows for increased life expectancy, overall survival, and objective response rates. Moreover, continuous improvements in radiation therapy techniques help reduce the incidence of early systemic radiation reactions. Thus, the daily split-dose dose RT is more effective and can be considered the preferred RT regimen for the treatment of inoperable patients with locally advanced pancreatic cancer.
The aim of the study was to systematize current data on the use of human epididymis protein 4 (HE4) as a tumor-associated marker for lung cancer (LC) diagnosis, prognosis of treatment response, and monitoring of this category of patients. Material and Methods. A search and analysis of available Russian and Englishlanguage sources was performed in the RSCI and PubMed databases using keywords “lung cancer” and “HE4”. The review includes 44 papers published between 2006 and 2024. Results. HE4 is involved in gynecological cancer progression, but its role in the development of LC remains poorly studied despite its high expression in tumor tissue. Modern studies demonstrate that diagnostic characteristics of serum HE4 are comparable to or slightly superior to other markers used in the diagnosis of LC (CYFRA21-1, CEA, NSE, ProGRP, etc.). Several studies report that the HE4 serum level can serve as a predictor of response to chemotherapy and the duration of the relapse-free interval in LC. Some studies indicate the feasibility of HE4 as a marker for monitoring patients for early detection of lung cancer relapse. The indicators of the diagnostic and prognostic signifcance of serum HE4 vary signifcantly in different studies due to the heterogeneity of the included groups, differences in the reference values and methods for assessing the HE4 levels. This does not allow us to adopt a unifed diagnostic algorithm for using HE4. Conclusion. The accumulated data indicate the feasibility of using HE4 as a tumor-associated marker in LC. However, some aspects that are important for the practical application of HE4 remain unclear. Thus, the introduction of this marker into clinical practice requires further systematic and in-depth studies.
Background. Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome characterized by marked polymorphism of clinical manifestations. There is evidence of genotypic correlations in NF1 with more pronounced manifestations of the disease with certain mutations in the NF1 gene. therefore, it is important to describe patients with a specific mutation and a severe NF1 phenotype.Purpose of the study: to describe the genetic and clinical features of NF1 and its treatment tactics in the patient with severe manifestations of the disease and a unique mutation in the NF1 gene.Material and Methods. A ten-year-old girl with a sporadic case of NF1 was examined, X-ray examination was performed, a blood sample was taken with DNA extraction and sanger sequencing of the NF1 gene.Results. The patient was identified to have a unique pathogenic variant c.240_241del(p.Y80fs) in the NF1 gene, and the following clinical manifestations of NF1: retrocerebellar brain cyst, femur plexiform neurofibroma, grade 3 scoliosis, and femur fibrous dysplasia. successful surgical correction of the scoliosis was performed. targeted therapy with selumetinib was prescribed for femur plexiform neurofibroma treatment.Conclusion. the identified NF1 variant: c.240_241del(p.Y80fs) has not previously been described in the scientific literature and is not included in the ClinVar database. the clinical manifestations of NF1, characterized by severe combined lesions, have been described. treatment of such cases of NF1 requires a combination of targeted therapy and high-tech surgery.
Background. Glioblastoma (GBM) is the most aggressive and malignant type of glioma, representing the most common and lethal primary central nervous system (CNS) neoplasm in adults. Despite current therapeutic approaches, the median overall survival remains low. Oncolytic virotherapy is a highly promising alternative strategy. One such approach utilizes the Herpes Simplex Virus Thymidine Kinase (HSV-TK) enzyme combined with the prodrug ganciclovir (GCV). This TK-GCV system is converted into a toxic metabolite that induces apoptosis in target cells. Combining the TK-GCV system with temozolomide (TMZ), the standard first-line chemotherapeutic agent for glioma, targets two critical survival mechanisms of GBM: DNA repair and apoptosis regulation. This combination has the potential to significantly improve therapeutic efficacy.Aim. We evaluated the impact of combined TK-GCV and TMZ therapy on glioblastoma cell viability and migratory capacity in vitro.Material and Methods. This work employed the following cell lines: GBM cell lines U87-MG and U251-MG, HEK293T/17 cells, and human mesenchymal stem cells. Recombinant viral particles encoding the thymidine kinase (TK) gene were generated using genetic engineering techniques. Optimal concentrations of TMZ and GCV were determined. Cell viability was assessed using the MTT assay; cell cycle distribution (G2/M phase) and Bax expression were analyzed by flow cytometry; gene expression was quantified via quantitative PCR (qPCR); and cell migration was measured using a wound-healing assay.Results. The combination of TMZ and the TK-GCV system results in a significant increase in GBM cell death compared to monotherapy. Specifically, this enhanced cell death is characterized by a higher proportion of apoptotic cells. Furthermore, expression levels of EMT markers such as CD44, ZEB1, SNAI1, SNAI2, and VIM were significantly reduced under the combined treatment of TK-GCV and TMZ.Conclusion. The combination of TK-GCV and TMZ demonstrates a synergistic effect between the two therapeutic approaches. Compared to each method administered separately, the combined treatment results in increased GBM cell death and reduced cell migration.
Study Objective: to provide an overview of current scientific data on the impact of H. pylori infection and eradication therapy on the development, clinical course and treatment outcomes of gastrointestinal cancer.Material and Methods. A search of Russian and English-language literature sources published in various databases (MedLine, Pubmed, Scopus, The Cochrane Library, and Russian Science Citation Index) between 2004 and 2025 was conducted. Fifty-three available scientific publications were analyzed, including 5 Russian and 48 foreign publications, including 41 articles, 10 meta-analyses, and 2 retrospective studies.Results. An analysis of scientific papers showed that H. pylori infection significantly worsened treatment outcomes and survival in patients with already diagnosed gastric cancer. Literature data demonstrate a positive impact of H. pylori eradication on survival in both early and advanced gastric cancer. In addition to being a major risk factor for stomach cancer, H. pylori infection is also associated with an increased risk of colorectal cancer, esophageal adenocarcinoma, pancreatic cancer, and biliary tract cancer. Furthermore, H. pylori infection impacts the effectiveness of immunotherapy in cancer treatmentConclusion. H. pylori infection and eradication therapy can influence the development and clinical course of gastrointestinal tumors. Despite the close attention of many scientists to this issue, key questions remain poorly understood.
Objective: to summarize current data on immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction, with an emphasis on hypophysitis and primary adrenal insufficiency.Material and Methods. A review of publications on endocrine immune-related adverse events from anti-CTLA-4, anti-PD-1 and antiPD-L1 inhibitors was carried out from January 2015 to October 2025 using Pubmed, Cochrane library, Google Scholar, and Elibrary systems. Of the 876 studies found, 45 were used to write the systematic review.Results. immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction is a serious immune-related adverse event. It commonly presents as hypophysitis (particularly with anti-CTLA-4, causing pituitary deficiency) and primary adrenal insufficiency (risking fatal Addisonian crisis). Diagnosis is complicated by the nonspecific clinical presentation. Essential evaluation includes assessing symptoms, adrenocorticotropic hormone, cortisol, electrolyte levels, and hormones of other axes, as well as magnetic resonance imaging of the pituitary gland and computed tomography of the adrenal glands. in most cases, long-term, and sometimes lifelong, hormone replacement therapy is required.Conclusion. Hypothalamic-pituitary-adrenal axis dysfunction associated with immune checkpoint inhibitor therapy remains underrecognized immune-related adverse event, requiring early recognition through clinician vigilance and screening algorithms to prevent adrenal crisis, improve quality of life and maintain cancer treatment efficacy. Multidisciplinary collaboration between oncologists and endocrinologists is particularly important in the care of these patients at all stages of treatment and follow-up.
The aim of the study was to study the effectiveness of combination of photodynamic therapy and immunotherapy in cancer treatment.Material and Methods. We searched and analyzed 843 publications available from WoS, Scopus, MedLine and RSCI databases over the past 5 years. Out of 843 articles, 60 were included in this review.Results. Preclinical and clinical data indicate the promise of combined photodynamic therapy, which is able to enhance the immune response and overcome resistance to PD-L1 inhibitors by destroying tumor vessels and improving antibody delivery. Photodynamic therapy is actively being investigated as a method of stimulating antitumor immunity, especially in combination with immunotherapy, turning “cold” tumors into “hot” ones. It promotes the growth of cytotoxic T-lymphocytes, suppresses regulatory T-lymphocytes and improves the interaction between tumor and effector cells, while disrupting regulatory mechanisms. Photodynamic therapy can also affect the expression of PD-L1/PD-1. Given the good tolerability of photodynamic therapy, its combination with immunotherapy can increase the effectiveness of treatment while minimizing the risks. Studies have shown that tumor mutation load and PD-L1 expression can predict treatment response in non-small cell lung cancer. In patients with lung adenocarcinoma with low/ moderate tumor mutation load and negative PD-L1, an improvement in overall survival was observed, which is consistent with data on the association of tumor mutation load with response to PD-L1 inhibitors. In the context of gastric cancer, the combination of photodynamic therapy with PD-L1 blockade has shown efficacy in restoring antitumor immunity by increasing the infiltration of cytotoxic T-lymphocytes and reducing the activity of regulatory T-lymphocytes.Conclusion. The combination of photodynamic therapy and immunotherapy has great potential, as photodynamic therapy destroys cancer cells and stimulates the immune response, and immunotherapy complements and enhances this effect.
Background. Prostate cancer is a leading malignancy among men worldwide, presenting signifcant public health challenges due to its complex biology and diverse clinical outcomes. Recent advances in bioinformatics have greatly infuenced cancer research by enabling the integration of multiple disciplines and improving the analysis of biological data. Objective. To present a comprehensive bibliometric analysis summarizing global research trends in prostate cancer and bioinformatics from 1998 to 2025. Material and Methods. A bibliometric study was conducted analyzing 3,426 articles sourced from 961 publications. Data on research output, collaboration patterns, citation impact, and thematic clusters were extracted and analyzed. Results. The feld exhibited a robust annual growth rate of 18.42 %, with an average document age of 5.65 years and 26.34 citations per article, indicating high scientifc impact. Collaborative research is prevalent, with 13,598 authors averaging 7.21 co-authors per publication and over 21 % of research produced via international partnerships. Publication formats included journal articles, reviews, and conference papers. Keyword cooccurrence analysis revealed fve main thematic clusters: computational and omics methodologies; tumor biology and immunology; molecular mechanisms and cancer progression; biomarkers and gene regulation; and interdisciplinary cancer research. Publication patterns indicated steady output before 2013 followed by a marked surge peaking near 500 articles in 2023, driven by advancements in genomics, big data analytics, and precision oncology. Citation data highlighted the United States and China as leading contributors, with China leading in publication count through predominantly domestic research, while the United States featured more international collaborations. Other signifcant contributors included Australia, Germany, Canada, and several European and Asian countries. Conclusion. Research at the intersection of prostate cancer and bioinformatics is rapidly expanding, highly collaborative, and globally distributed. The multidisciplinary and integrative nature of this feld continues to advance understanding, diagnosis, and treatment of prostate cancer through cutting-edge bioinformatics approaches.
Background. Bladder cancer is the 10th most common cancer worldwide and the most common malignancy of the urinary tract. Non-muscle invasive bladder cancer accounts for approximately 80 % of cases. Tumors localized in the anterior bladder wall may be challenging to resect completely due to diffcult visual access. Here we present a case of non-muscle invasive bladder cancer localized in a diffcult-to-access area. Case report. A 67-year-old patient with a mass on the anterior wall of the bladder underwent Nd:YAG laser ablation of non-muscle-invasive bladder cancer of diffcult localization in the urological hospital of the Russian Railways-Medicine Central Clinical Hospital. The previous histological examination of the biopsy specimen of the bladder mass reveled bladder cancer. The superfcial tumor growth was confrmed by preoperative MRI fndings. The Nd:YAG laser with a wavelength of 1064 nm, a power of 40 W and an energy density of 100 J/cm2 was used. The laser beam was delivered through a side fre light guide. After surgery, a two-way catheter was inserted into the bladder for 12 hours. No intraoperative and postoperative complications were detected. Endoscopic evaluation of the effectiveness of the surgical stage was carried out at intervals of 3, 6 and 12 months from the date of surgery. Control cystoscopy revealed no cancer recurrence. Conclusion. Our clinical case demonstrated the high effcacy and safety of Nd:YAG laser ablation in the treatment of a patient with non-invasive bladder cancer located on the anterior wall of the bladder.
The purpose of the study was to evaluate the effect of perioperative bronchodilator therapy on the incidence of postoperative complications and survival in non-small cell lung cancer (NSClC) patients with chronic obstructive pulmonary disease (COPD).Material and Methods. The study included 66 patients with stage IВ–IIIА NSCLC and stage I–III COPD, who were divided into 3 groups. Group 1 consisted of 22 patients who received tiotropium bromide (a long-acting bronchodilator) for 6 weeks before and 6 weeks after surgery. Group 2 consisted of 21 patients, who received ipratropium bromide/fenoterol (a short-acting bronchodilator) for 6 weeks before and 6 weeks after surgery. Group 3 (control group) comprised 23 patients who received ipratropium bromide/fenoterol for 6 weeks after surgery. Patients of groups 1 and 2 received 2 courses of neoadjuvant carboplatin-based chemotherapy. All patients underwent radical surgery: lobectomy (47 %), bilobectomy (22.7 %) and pneumonectomy (30.3 %). Postoperative complications were classified according to the TMM system (2010). One-year survival was estimated using the Kaplan–Meier method; curve comparisons were performed using the log-rank test.Results. Postoperative complications were observed in 9 (40.9 %), 14 (66.7 %) and 18 (78.3 %) patients of groups 1, 2 and 3, respectively. Significant statistical differences between group 1 and the control group were found (р˂0.05). The rate of grade ii postoperative respiratory complications was significantly lower in group 1 than in groups 2 and 3 (18.2 % vs 52.4 % and 65.2 %, respectively, р˂0.05). One-year relapse-free and overall survival rates were significantly higher in group 1 patients than in the control group (80 % vs 47.6 % (p=0.032) and 90 % vs 61.9 %, (p=0.037) respectively). In group 2 patients, the relapse-free and overall survival rates were lower than in group 1 patients, but were higher than in the control group (73.7 % (р=0.093) and 89.5 % (р=0.045), respectively).Conclusion. In patients with NSClC and COPD, perioperative bronchodilator therapy with tiotropium bromide was more effective and associated with a lower incidence of postoperative pulmonary complications than ipratropium bromide/fenoterol therapy, and in combination with neoadjuvant chemotherapy contributed to improved survival rates. Long-term treatment results require further research.
Introduction. Parameningeal rhabdomyosarcoma with intracranial spread is a highly aggressive pediatric malignancy with a high risk of leptomeningeal metastasis. Historically, central nervous system (CNS) involvement was considered an incurable condition with a survival rate of no more than 10–20 %. The bloodbrain barrier is the primary barrier to the penetration of most drugs and the creation of effective concentrations. Therefore, the search for effective and non-toxic methods for controlling leptomeningeal metastases is one of the most pressing challenges in pediatric oncology. Intrathecal chemotherapy (ITCT) delivers cancer drugs directly into the cerebrospinal fuid, bypassing the BBB. It enables high concentrations of medication to directly target cells, reducing systemic toxicity. The purpose of the study was to evaluate the effcacy and safety of intrathecal chemotherapy in a multidisciplinary approach to the treatment of children with parameningeal rhabdomyosarcoma with intracranial spread and/or leptomeningeal metastasis, and to improve survival rates in this cohort of children. Material and Methods. The study included 21 patients with a histologically verifed diagnosis of parameningeal rhabdomyosarcoma with intracranial spread and/or leptomeningeal metastasis, who received treatment at the L.A. Durnov Research Institute of Pediatric Oncology and Hematology of the Russian Academy of Medical Sciences from 2021 to 2024. The study was approved by the local ethics committee. Results. With a 34.3-month median follow-up, the overall 2-year survival rate was 65 %. This indicates the effectiveness of early tumor control by overcoming the blood-brain barrier. The overall 2-year survival rate was signifcantly higher in both the prophylactic and therapeutic frst-line intrathecal chemotherapy groups than in the relapse group (80 % vs 20 %, p<0.05) and signifcantly exceeded the median survival time of 4–6 months reported by other authors [1]. The toxicity profle of ITCT was favorable, with no cases of severe neurotoxicity. Conclusion. Intensive intrathecal chemotherapy in the combination treatment of children with parameningeal rhabdomyosarcoma with intracranial extension and/or leptomeningeal metastasis is an effective and safe method for treating and preventing CNS tumor cell infltration. This therapy can signifcantly improve survival of patients with extremely unfavorable prognosis.
Objective: to develop a preoperative model for predicting 90-day mortality to optimize treatment strategy in patients with resectable esophageal cancer and Siewert type I gastroesophageal junction cancer.Material and Methods. A retrospective cohort study included 225 patients with resectable esophageal cancer (n=179) and Siewert type I gastroesophageal junction cancer (n=46). A total of 79 preoperative variables were analyzed. Risk factors were selected using univariate and multivariate logistic regression. The dataset was randomly split into training and validation cohorts (70/30). The predictive model was developed using l1-regularized multivariable logistic regression and the TabNet neural network featuring a sparse attentive architecture that enables estimation of feature importance. Discriminative ability and calibration were assessed using AUCROC analysis and the Hosmer–Lemeshow test.Results. The in-hospital mortality, 30-day mortality and 90-day mortality rates were 8.9 % (n=20), 1.3 % (n=3), and 6.2 % (n=14), respectively. The most significant predictors of mortality included preoperative weight loss >10 %, grade 3–4 dysphagia, ECOG performance status ≥2, COPD, preoperative dyspnea, history of major thoracic surgery, TNM stage N2, tumor proximity to or invasion of the trachea/main bronchi, cerebrovascular disease history, diabetes mellitus, and complications during or after radiotherapy. The logistic regression model demonstrated an AUC-ROC of 0.86 (95 % Ci 0.79–0.92) in the training cohort and 0.77 (95 % CI 0.72–0.83) in the validation cohort. Calibration was supported by non-significant Hosmer–Lemeshow χ2 tests in both cohorts: χ2=1.98, df=8 (p=0.98) and χ2=4.72, df=8 (p=0.78), respectively. The TabNet neural network achieved improved discrimination with AUC-ROC values of 0.95 (95 % CI 0.92–0.98) in the training cohort and 0.86 (95 % Ci 0.82–0.96) in the validation cohort; calibration results were χ2=8.38, df=8 (p=0.39) and χ2=9.46, df=8 (p=0.30), respectively. The model has been implemented as a software application and can be used in real-world clinical scenarios.Conclusion. In this study, a machine learning-based model for preoperative 90-day mortality prediction was developed. It demonstrated good validity and high discriminative performance. The findings support the promise of machine learning methods for clinical risk prediction in cancer surgery and highlight their potential for implementation in routine healthcare practice.
Background. Expression of the main mediators of infammatory signaling – cytokines and long non-coding RNAs (lncRNAs) – determines the course of the tumor process and the formation of a platinum-insensitive phenotype in ovarian cancer. The aim of the study was to evaluate the co-expression of long non-coding RNAs HOTAIR, MALAT1, PVT1 with proinfammatory cytokines in blood plasma during the formation of a platinum-insensitive phenotype in ovarian cancer. Material and Methods. The study included 46 patients with primary ovarian cancer treated at the Ulyanovsk Oncology Center in 2018–2020. RNA was isolated from 2 ml of patients’ blood plasma before treatment, followed by reverse transcription and polymerase chain reaction to analyze the expression of HOTAIR, MALAT1, and PVT1. Plasma levels of the cytokines IL-1β, -10, -17A, and -18 were also determined. Ovarian cancer patients were divided into 2 groups based on the duration of the platinum-free interval. Results. Plasma expression of long non-coding RNAs (lncRNAs) HOTAIR, MALAT1, and PVT1 was found to be signifcantly higher in patients with ovarian cancer than in patients with benign ovarian tumors. Plasma HOTAIR expression was also higher in stages III–IV ovarian cancer compared to stages I–II. Patients with platinum-insensitive ovarian cancer had signifcantly lower levels of IL-17A and IL-10 compared to patients in the comparison group, but higher levels of IL-1β and IL-10 compared to patients in the platinum-sensitive group. A correlation was found between the levels of lncRNA MALAT1 and IL-18. Conclusion. The serum expression level of PVT1 lncRNA in ovarian cancer patients correlates with progression-free survival and allows for assessing the likelihood of disease recurrence. Serum coexpression of MALAT1 and IL-18 lncRNAs can be used as a predictive marker for identifying platinuminsensitive ovarian cancer. Their combined overexpression with proinfammatory cytokines and IL-1β before chemotherapy has prognostic potential as a marker of platinum resistance in ovarian cancer. A prognostic model for assessing the risk of cancer progression in the frst 6 months after diagnosis includes MALAT1 and HOTAIR expression data at the start of therapy and serum IL-1β and -18 levels. A K-value above 1.65 indicates a high risk of disease progression.
Introduction. The melanocortin-1 receptor (MC1R) gene is one of the key factors in susceptibility to cutaneous melanoma (CM). The influence of specific germline MC1R polymorphisms on disease aggressiveness, tumor morphology, and patient survival has not been sufficiently studied.Objective: to comprehensively assess the associations of five key polymorphic variants of the MC1R gene (R151C, R160W, D294H, R163Q, I155T) with constitutional characteristics, primary tumor parameters, overall survival (OS), and event-free survival (EFS) in patients with CM.Material and Methods. A single-center retrospective cohort study included 213 patients with primary CM at stages I–III. Genotyping was performed using allele-specific real-time PCR with melting curve analysis. The χ2 test, Fisher’s exact test, and Mann-Whitney U test were used. Survival analysis was conducted using the Kaplan-Meier method with the log-rank test; multivariate Cox regression was applied to identify independent prognostic factors.Results. Specific phenotypic profiles were established: R151C was associated with male sex, skin phototype I–II, and a history of severe sunburns (p<0.05); R160W was associated with the “red hair/ freckles” phenotype (p<0.05). Carriers of R151C had tumors with greater thickness (p<0.001). The most significant differences were found in prognosis: carriers of the D294H and I155T alleles demonstrated the lowest survival rates. The five-year OS for D294H was 28.4 % compared to 66.7 % in the wild-type group (p<0.001). In the adjusted model, only D294H (HR=4.21; 95 % CI 1.92–8.97; p<0.001) and I155T (HR=3.72; 95 % CI 1.65–8.39; p=0.001) remained independent predictors of unfavorable OS. The influence of R151C on the outcome was mediated by unfavorable morphological features.Conclusion. The contribution of MC1R polymorphisms to the course of CM is heterogeneous. The D294H and I155T alleles are independent determinants of an extremely unfavorable prognosis, while R151C serves as a marker of a high-risk phenotype and a locally aggressive tumor, and R160W determines only a constitutional phenotype. The data obtained justify the feasibility of integrating genotyping for the D294H and I155T variants into risk stratification algorithms to personalize follow-up for patients with CM.
Tumor microenvironment acidity represents a fundamental hallmark of cancer that promotes tumor progression, invasion, immune evasion, and treatment resistance. Objective. This study investigates the antitumor mechanisms of sodium bicarbonate-induced alkalization on mouse colon adenocarcinoma CT26 cells and human melanoma cells. Material and Methods. Cells were treated with varying sodium bicarbonate concentrations (50–119 mM) to assess effects on viability, metabolism, migration, and cell death pathways. Results. Results demonstrated immediate concentration-dependent extracellular pH elevation that decreased after 24 hours due to metabolic adaptation. Both cell lines exhibited dose-dependent cytotoxicity with an IC50 of approximately 80–90 mM, yet minimal apoptosis was detected via Annexin V/PI staining, suggesting alternative cell death mechanisms. Sodium bicarbonate signifcantly impaired cellular migration in wound healing assays, coinciding with mitochondrial depolarization as evidenced by reduced Mito Red fuorescence. Metabolic analysis revealed increased consumption of glucose and glutamine alongside elevated lactate production, indicating metabolic reprogramming in response to alkalization stress. While lysosomal accumulation increased with treatment (measured by Lyso Green), canonical autophagy markers (LC3B and p62) showed no signifcant changes, suggesting classical autophagy pathways are not primarily involved. Conclusion. These fndings indicate that sodium bicarbonate-induced alkalization triggers tumor cell death through mechanisms beyond conventional apoptosis and autophagy, potentially involving lysosome-mediated cell death or alkaliptosis. The study provides mechanistic insights supporting sodium bicarbonate as a potential adjuvant therapy that targets the tumor microenvironment’s acidity, with implications for enhancing conventional cancer treatments through pH modulation. Further research is needed to fully elucidate the precise cell death pathways involved.
