The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms in the development of resistance remain poorly understood. The BT-474 cell line was selected as an optimal model for study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify the molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multistep bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during the development of resistance were identified. The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.

Currently, due to the lack of clear criteria for predicting the aggressive course of pituitary adenomas (APA), the search for diagnostic markers is highly relevant. Genetic markers, among others, may serve as such markers since their identification is possible at early stages of the pathological process.

Radical cystectomy is recognized as the gold standard in the management of muscle-invasive bladder cancer. However, despite its definitive nature, recurrences of urothelial carcinoma in the upper urinary tract remain an important cause of morbidity and mortality during long-term follow-up. The prognosis of such recurrences is generally poor, largely due to delayed diagnosis. This article presents three clinical cases of upper urinary tract recurrence detected 16-24 months after radical cystectomy. Successful treatment was achieved with radical nephroureterectomy including excision of the adjacent intestinal segment. These cases highlight the effectiveness of this surgical approach for upper tract recurrences following radical cystectomy and emphasize the need to establish criteria to determine whether urothelial tumors in the upper urinary tract represent true recurrences of bladder cancer or previously undiagnosed primary lesions. Further studies are required to develop algorithms for the early detection and management of this relatively rare pattern of disease progression.

Aggressive disease course, recurrences, and deterioration of patients quality of life remain significant challenges in the treatment of bladder cancer. Determining the indications for systemic therapy or radical treatment, the early detection, and the optimal timing for initiating adjuvant therapy are all crucial aspects in the management of urothelial carcinoma. The analysis of the literature on changes in diagnostics and therapeutic approaches to urothelial bladder cancer according to disease stage is presented in the article.

To evaluate diagnostic significance of IL-6 compared to CRP for early detection of anastomotic leakage after colon resection for colorectal cancer.

To study the results of treatment of cancer in tubular villous colorectal adenomas.

To demonstrate the effectiveness and safety of intraluminal endoscopic treatment of patients with adenomas of the major duodenal papilla and familial adenomatous polyposis.

The epidemiological data on the incidence of gastric cancer and its mortality make it a challenge for oncologists to find new and improve existing diagnostic methods and therapies. Despite the active change of modern realities in the practice of pathomorphologist for 60 years remains unchanged authority of the P.Laurén classification of histological main types. This does not leave it without attention from the scientists of our time, so there are published works refuting or confirming its prognostic significance, as well as studies in which its modifications are proposed. In this regard, the purpose of this review is to briefly systematise the currently available information on P.Laurén classification and to provide an opportunity to review the content of the original article by Pekka Laurén in Russian.

Disorders of sex development or hermaphroditism are a condition associated with a discrepancy between genetic, gonadal, and phenotypic sex. Persistent Müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism. Typical features are cryptorchidism and the presence of underdeveloped fallopian tubes, uterus or upper vagina in a male with karyotype 46, XY. Over the past 50 years, about 200 cases of persistent Müllerian duct syndrome have been reported. The article describes an observation of a 33-year-old patient with bilateral cryptorchidism, testicular neoplasm, and false hermaphroditism revealed during the examination of surgical material. Macroscopic and microscopic pictures are presented, including those using immunohistochemical methods. The results of a molecular genetic study of the surgical material are given. After all the examinations, the patient was diagnosed with: Typical seminoma of the right undescended testicle, pT2. False hermaphroditism.

The degree of pathologic response in non-small cell lung cancer (NSCLC) after neoadjuvant therapy (NAT) has prognostic impact as well as influence on patient's management. It was shown that the best survival rates were achieved in patients with equals or less than 10% of residual carcinoma (major pathologic response) or with complete absence of invasive carcinoma (complete pathologic response). In 2020 the International Association for the Study of Lung Cancer has published Multidisciplinary Recommendations for pathologic assessment of NSCLC resection specimens after NAT. In this article, we present the main points of the Recommendations taking into account our own experience in evaluating post-therapeutic changes in NSCLC. The article is intended primarily for pathologists practicing in oncological hospitals, but may also be of interest to other practitioners involved in the diagnostics and treatment of lung cancer patients.

To evaluate the impact of combined anti-PD-1 immunotherapy on the cellular composition of the tumor microenvironment in patients with gastric cancer.

The question of the degree of influence of uterine artery embolization (UAE) on fertility is open. It is important to evaluate the pathomorphological structure and functional activity of the endometrium, the disruption of which can lead to infertility.

To detect the presence or absence of correlations between the degree of tumor budding (TB) and pMMR/dMMR (proficient Mismatch Repair System/deficient Mismatch Repair System) and PD-L1 status in gastric cancer (GC).

Primary squamous cell carcinoma of the orbit is rare, as this area does not have its own squamous epithelium. Tumors of this localization are caused either by the germination of the primary focus located on the skin of the face or in the paranasal sinuses, or by the spread of the tumor through perineural invasion. The difficulty of surgical treatment of this localization is that with standard access it is often impossible to visualize the posterior edge of the resection, which, in turn, can lead to a recurrence of the tumor process. Our center uses the endonasal access technique, which facilitates satisfactory visual control of the posterior edge of the resection, and also avoids incisions on the face. This article describes a clinical case of cancer treatment of the ethmoid labyrinth.

Analysis of a clinical case of successful removal of odontogenic keratocyst of the mandible using methods of differential diagnostic, clinical and X-ray analyses and by forming several bone windows.

To study the dental status of patients depending on the presence of precancerous diseases of the oral mucosa.

Identification the characteristics of fatty acids (FAs) in erythrocyte membranes and in blood serum, as well as the electrical and viscoelastic parameters of erythrocytes to assess their ability to be predictors of an unfavorable outcome in patients with colorectal cancer (CRC).

To develop a treatment strategy based on the analysis of clinical manifestations and the results of morphofunctional diagnostics for patients with gastroesophageal reflux disease (GERD) aimed at preventing the development and progression of intestinal metaplasia (IM) of the esophageal epithelium.

We present a clinical case of cancer-associated ischemic stroke in a 70-year-old patient with metastatic sigmoid colon cancer. The patient was admitted to the hospital in the hyperacute stage of ischemic stroke due to thrombosis of the left middle cerebral artery, complicated by severe global aphasia and right-sided hemiplegia (NIHSS - 20). Despite the high risk of hemorrhagic complications associated with underlying malignancy, systemic thrombolysis with alteplase was successfully administered; however, hemorrhagic transformation subsequently occurred. Early comprehensive rehabilitation and adjunctive therapy with Cerebrolysin (30 ml/day) significantly reduced neurological deficits. One month after the stroke, the patient exhibited near-complete motor recovery and substantial improvement in speech function without complications during anticoagulant therapy with apixaban. This case highlights the importance of early diagnosis and an integrated approach to the management of stroke in oncological patents.

Infection with tick-borne encephalitis virus (TBEV) can lead to severe neurological complications largely associated with the activation of innate immunity and inflammatory reactions in the tissues of the nervous system. In this regard, the study of factors, including viral factors, influencing these processes is underway. We analyzed the possible role of nonstructural protein 1 (NS1) of TBEV in the activation of innate immune response reactions in cells of the nervous system. SH-SY5Y neuroblastoma and DBTRG-05MG glioblastoma cells were transfected with a plasmid encoding NS1 or treated with extracellular vesicles of NS1-expressing HEK293T cells and then stimulated with polyinosinic-polycytidylic acid [poly(I:C)] to activate the innate immune response. It was found that poly(I:C) stimulation of NS1-expressing SH-SY5Y cells resulted in lower mRNA levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), as well as the innate immune response of the cytokine interferon-1β(IFN-β) and the interferon-stimulated gene 15 product (ISG15), compared to stimulated cells without NS1 expression. In addition, transcription of the sensor gene MDA5, which is responsible for activating gene transcription of these cytokines, was reduced in these cells. In NS1-expressing DBTRG-05MG stimulated cells, only the IL-1β mRNA content was reduced. Treatment of SH-SY5Y cells with extracellular vesicles from NS1-expressing cells followed by poly(I:C) stimulation resulted in increased mRNA levels of IL-6, TNF-α, and IFN-β, compared with stimulated cells treated with vesicles from non-NS1-expressing cells. No differences were detected in DBTRG-05MG cells with similar treatment. Based on these data, we can assume that TBEV NS1 plays a dual role in the formation of neuroinflammation during the infection, and we can consider this protein as a potential therapeutic target.