Evgeny V. Denisov

Tomsk National Research Medical Center · Laboratory of Cancer Progression Biology

Brain-derived neurotrophic factor (BDNF) is a secreted molecule that plays an important role in the survival and growth of nerve cells. BDNF undergoes complex post-translational processing with cellular proteases. Pro- and mature BDNF forms bind to different receptor types in the brain. BDNF is prominent in the neonatal cerebral cortex. The neonata...

Background: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we...

One of the predictors of adverse prognosis in breast cancer is the overexpression of the EpCAM protein. However, a signifcant part of tumor cells have low or no EpCAM expression. The molecular features and the ability to grow in 2D and 3D cultures, indirectly refecting metastatic potential of tumor cells without EpCAM expression, have not been suff...

Molecular genetic analysis of tumor tissues is the most important step towards understanding the mechanisms of cancer development, and it is also necessary for the choice of targeted therapy. Hi-C (high-throughput chromatin conformation capture) technology can be used to detect various types of genomic variants, including balanced chromosomal rearr...

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study...

Introduction Perivascular epithelioid cell tumors (PEComa) are rare mesenchymal neoplasms characterized by perivascular epithelioid cells. Despite their common occurrence in the uterus, gastrointestinal tract, and retroperitoneum, this study presents an exceptional case of PEComa identified in the lung, warranting unique molecular exploration. Cas...

Most studies on CTCs have focused on isolating cells that express EpCAM. In this study, we emphasize the presence of EpCAM-negative and EpCAMlow CTCs, in addition to EpCAMhigh CTCs, in early BC. We evaluated stem cell markers (CD44/CD24 and CD133) and EMT markers (N-cadherin) in each subpopulation. Our findings indicate that all stemness variants w...

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms which regulate metabolism, immune function and health. There are 3 types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokin...

In this work, we have analyzed the transcriptomic changes in the brainstem of male Wistar rats 2 h after an acute stress exposure. We performed duplex-specific nuclease normalization of cDNA libraries and compared the results back-to-back for the first time. Based on our RNAseq data, we selected reference genes for RT-qPCR that are best suited for...

To identify genetic alterations associated with tongue cancer recurrence in young adults, whole exome sequencing of the primary tumor, recurrence, and whole blood samples from young patients with tongue cancer was performed. A frameshift mutation in the TP53 gene was detected in the primary tumor and recurrence tumor tissue. A mutation in the EPHB6...

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancer...

A benefit of biomedical application of nanosystems is implementation of a precise effect at the level of an individual cell, and magnetic nanoparticles (MNPs) are some of the best candidates for the development of an intelligent nanosystem with remote control. To develop a nanosystem for precise therapy, a deep understanding of the nanosystem’s in...

Following the discovery of circulating tumor cells (CTCs) in the peripheral blood of cancer patients, CTCs were initially postulated to hold promise as a valuable prognostic tool through liquid biopsy. However, a decade and a half of accumulated data have revealed significant complexities in the investigation of CTCs. A challenging aspect lies in t...

Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno‐oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte a...

Molecular genetic analysis of tumor tissues is the most important step towards understanding the mechanisms of cancer development; it is also necessary for the choice of targeted therapy. The Hi-C (high-throughput chromatin conformation capture) technology can be used to detect various types of genomic variants, including balanced chromosomal rearr...

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cyt...

Introduction. Squamous cell carcinoma (SCC) of the oral cavity is an aggressive and rapidly progressing disease. The tendency to progression of the tumor process is due to the clinical and pathological characteristics of the patient and the biological characteristics of the tumor. molecular and genetic disorders related with transcriptome level pla...

Osteogenic differentiation is crucial in normal bone formation and pathological calcification, such as calcific aortic valve disease (CAVD). Understanding the proteomic and transcriptomic landscapes underlying this differentiation can unveil potential therapeutic targets for CAVD. In this study, we employed the timsTOF Pro platform to explore the p...

Early prediction and prevention of recurring illness is critical for improving the survival rates of patients with non-small cell lung cancer (NSCLC). Previously, we demonstrated that the presence of premalignant epithelial changes in the small bronchi distant to the primary tumor is associated with NSCLC progression: isolated basal cell hyperplasi...

Background: Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. I...

Background Integrins enable cell communication with the basal membrane and extracellular matrix, activating signaling pathways and facilitating intracellular changes. Integrins in circulating tumor cells (CTCs) play a significant role in apoptosis evasion and anchor-independent survival. However, the link between CTCs expressing different integrin...

Oral cancer (OC) is the most common cancer of the head and neck. Tongue cancer (TC) is the most frequently diagnosed form of OC and is characterized by a high aggressiveness and progression. OC and TC are considered diseases of the elderly, but the incidence among young adults (under 45 years) is increasing every year. The etiological factors and p...

Soft tissue sarcomas are rare tumors (about 1 % of all malignant neoplasms) and include more than 70 histological subtypes, the pathogenetic features of which remain unclear. This is largely due to both quantity and volume of clinical material and high heterogeneity of the disease. Given the rarity and heterogeneity of each individual subtype of so...

Mesenchymal stem cells (MSCs) are widely used in therapy, but the differences between MSCs of various origins and their ability to undergo osteogenic differentiation and produce extracellular matrix are not fully understood. To address this, we conducted a comparative analysis of mesenchymal cell primary cultures from 6 human sources, including ost...

To study the mechanisms of metastasis, one of the effective tools is mouse models using primary patient tumors (Patient-Derived Xenograft, PDX). The phenomenon of changes in the cell phenotype in response to the dynamic conditions of the tumor microenvironment is one of the key processes forming the basis for metastasis.

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2...

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study...

Рак полости рта (РПР) – наиболее распространенный тип злокачественных новообразований головы и шеи. При этом рак языка (РЯ) представляет собой наиболее часто встречающуюся форму РПР и характеризуется более агрессивным течением и высокой вероятностью прогрессирования. РПР и РЯ считаются заболеваниями пожилых людей, однако их встречаемость среди лиц...

Circulating tumor cells (CTC) are the root cause of life-threatening cancer metastases. The rare CTC cannot be specifically killed by anti-cancer agents without producing any side effects, nor be targeted-and-eradicated by antibody or aptamer complexes because of the complexes’ limited circulating half-life in the blood owing to metabolism and immu...

Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood that develops due to mutations in the genes of the RAS-signaling pathway. Next-generation high throughput sequencing (NGS) enables identification of various secondary molecular genetic events that can facilitate JMML progression and transformation into s...

Background: Squamous cell lung cancer (SCLC) arises from bronchial changes: basal cell hyperplasia (BCH), squamous metaplasia (SM), and dysplasia. However, the premalignant process preceding SCLC is not inevitable; it can stop at any of the bronchial lesions. Previously, we hypothesized that combinations of premalignant lesions observed in the sma...

Cancers are one of the leading causes of mortality in the world. Cellular and physiological mechanisms of cancer development remain not well defined. In vivo models are an attractive approach for understanding of cancer origin and progression. This review presents current state of experimental in vivo systems including syngeneic models, patient-der...

Секвенирование РНК единичных (отдельных/индивидуальных) клеток (single-cell RNA-sequencing, scRNA‑seq) является революционным инструментом для изучения физиологии нормальных и патологически изменённых тканей. Данный подход предоставляет информацию о молекулярных особенностях (генной экспрессии, мутациях, степени открытости хроматина и др.) клеток,...

Single-cell RNA sequencing (scRNA-seq) is a revolutionary tool for studying the physiology of normal and pathologically altered tissues. This approach provides information about molecular features (gene expression, mutations, chromatin accessibility, etc.) of cells, opens up the possibility to analyze the trajectories/phylogeny of cell differentiat...

Background The Illumina sequencing systems demonstrate high efficiency and power and remain the most popular platforms. Platforms with similar throughput and quality profiles but lower costs are under intensive development. In this study, we compared two platforms Illumina NextSeq 2000 and GeneMind Genolab M for 10x Genomics Visium spatial transcri...

Introduction Tumor resistance to chemotherapy and metastatic relapse account for more than 90% of cancer specific mortality. Tumor-associated macrophages (TAMs) can process chemotherapeutic agents and impair their action. Little is known about the direct effects of chemotherapy on TAMs. Methods The effect of chemotherapeutic platinum agent cisplat...

Despite considerable advances in the evolution of anticancer therapies, metastasis still remains the main cause of cancer mortality. Therefore, current strategies for cancer cure should be redirected towards prevention of metastasis. Targeting metastatic pathways represents a promising therapeutic opportunity aimed at obstructing tumor cell dissemi...

The problem of finding more precise stratification criteria for identifying the cohort of patients who would obtain the maximum benefit from immunotherapy is acute in modern times. In our study were enrolled 18 triple-negative breast cancer patients. The Ventana SP142 test was used for PD-L1 detection. Spatial transcriptomic analysis by 10x Genomic...

This study demonstrates the features of oral squamous cell carcinoma microbiome profile in young adults (<45 years) and its association with disease progression.

Background . Cancer of unknown primary (CUP) is a metastatic lesion with diffcult identifcation of the primary tumor site using standard diagnostic approaches. Although the incidence of CUP is not high, this type of cancer often shows a high aggressiveness and therapy resistance and results in poor patient survival. The mechanisms of CUP origin are...

Background . To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant me...

The review is devoted to the current state and prospects for the treatment of young adults with oral cancer. The article analyzes the possible methods of treatment for this category of patients: cytostatic and molecular therapy of oral cancer in young adults.

Whole exome sequencing of invasive mammary carcinomas revealed the association of mutations in PTEN and ZFHX3 tumor suppressor genes (TSGs). We generated single and combined PTEN and ZFHX3 knock-outs (KOs) in the immortalized mammary epithelial cell line MCF10A to study the role of these genes and their potential synergy in migration regulation. In...

The spread of tumor cells throughout the body by traveling through the bloodstream is a critical step in metastasis, which continues to be the main cause of cancer-related death. The detection and analysis of circulating tumor cells (CTCs) is important for understanding the biology of metastasis and the development of antimetastatic therapy. Howeve...

Circulating tumor cells and hybrid cells formed by the fusion of tumor cells with normal cells are leading players in metastasis and have prognostic relevance. This study applies single‐cell RNA sequencing to profile CD45‐negative and CD45‐positive circulating epithelial cells (CECs) in nonmetastatic breast cancer patients. CECs are represented by...

Mouse models using primary patient’s tumors (patient-derived xenograft, PDX) are an effective tool for studying the mechanisms of metastasizing. Tumor plasticity, i.e. the phenomenon of cell phenotype change in response to dynamic microenvironmental conditions is one of the key processes basic to metastasizing.

Background: Ewing sarcoma (ES) cells exhibit extreme plasticity that contributes to the cell’s survival and recurrence. Although multiple studies reveal various signaling pathways mediated by the EWSR1/FLI1 fusion, the specific transcriptional control of tumor cell resistance to doxorubicin is unknown. Understanding the molecular hubs that contribu...

Heart valve calcification is an active cellular and molecular process that partly remains unknown. Osteogenic differentiation of valve interstitial cells (VIC) is a central mechanism in calcific aortic valve disease (CAVD). Studying mechanisms in CAVD progression is clearly needed. In this study, we compared molecular mechanisms of osteogenic diffe...

The spread of tumor cells from the primary focus, metastasis, is the main cause of cancer mortality. Therefore, anticancer therapy should be focused on the prevention of metastatic disease. Key targets can be conditions in the primary tumor that are favorable for the appearance of metastatic cells and the first steps of the metastatic cascade. Here...

Radiotherapy (RT) is considered as a standard in the treatment of most solid cancers, including glioblastoma, lung, breast, rectal, prostate, colorectal, cervical, esophageal, and head and neck cancers. The main challenge in RT is tumor cell radioresistance associated with a high risk of locoregional relapse and distant metastasis. Despite signific...

Oral squamous cell carcinoma (OSCC) is one of the most important medical and socio-economic problems in many of the developed countries worldwide, due to the high mortality. The incidence of OSCC among individuals under 45 years of age is growing every year; however, the aetiological factors and pathogenetic mechanisms are poorly understood. This r...

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate, and avo...

Circulating tumor cells (CTCs) and tumor hybrid cells, being the leading players in metastasis, have prognostic relevance and are potential antimetastatic targets. CTCs are identified as epithelial-positive and CD45 (leukocyte)-negative cells, whereas tumor hybrid cells usually have epithelial and leukocyte components. However, epithelial and hybri...

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate and avoi...

Background The study assessed the possibility of dividing patients into groups based on the assessment of morphological changes in the epithelium of small-caliber bronchi located near the primary tumor in order to predict high and low risks of distant metastasis of non-small cell lung cancer. Methods In 171 patients with non-small cell lung cancer...

Currently, approaches to the choice of treatment tactics for cervical cancer have changed significantly. According to the recommendations of ESGO (2018), RUSSCO (2020), the use of a combination of surgical treatment and radiation therapy significantly increases the incidence of complications. Therefore, when planning the treatment of patients with...

Metastasis is the main cause of cancer death. Metastatic foci are derived from tumor cells that detach from the primary tumor and then enter the circulation. Circulating tumor cells (CTCs) are generally associated with a high probability of distant metastasis and a negative prognosis. Most CTCs die in the bloodstream, and only a few cells form meta...

Despite advances in diagnostics and therapy of non-small cell lung cancer (NSCLC), the problem of prognosis and prevention of tumor progression is still highly important. Even if NSCLC is diagnosed in the early stages, almost a quarter of patients develop relapse; most of them die from recurrent disease. A large number of different markers have bee...

Despite advances in diagnostics and therapy of non-small cell lung cancer (NSCLC), the problem of prognosis and prevention of tumor progression is still highly important. Even if NSCLC is diagnosed in the early stages, almost a quarter of patients develop relapse; most of them die from recurrent disease. A large number of different markers have bee...

To date, there is indisputable evidence of significant CTC heterogeneity in carcinomas, in particular breast cancer. The heterogeneity of CTCs is manifested in the key characteristics of tumor cells related to metastatic progression – stemness and epithelial–mesenchymal (EMT) plasticity. It is still not clear what markers can characterize the pheno...