Annexin A8 (ANXA8) is a member of the annexin family, which had been reported to regulate multiple cancer cellular processes including proliferation, metastasis and inflammation. However, the specific role of ANXA8 in lung cancer cell biology remains unknown. Our previous transcriptome study revealed that ANXA8 mRNA was downregulated in curcumin analog (MHMD) -treated human non-small lung cancer cells (A549 cell line). Here, we continued to study the ANXA8 expression in A549 cells using reverse transcription-quantitative PCR and Western blotting, compared with that in human normal bronchial epithelium cells (BE-AS-2B cell line). Overexpression of ANXA8 via transfection of pEGFP-ANXA8 recombinant vector contributed to the proliferation and migration of A549 cells. Moreover, the cell cycle protein cyclin E1 was upregulated in ANXA8-transfected A549 cells. Knockdown of ANXA8 using an RNA interference technique decreased A549 cell viability and restrained their migration in vitro. The expression levels of multiple cellular factors, including EGFR, PI3K, Akt, mTOR, p70S6K and 4EBP1, in the epidermal growth factor receptor (EGFR) signaling pathway were also altered by ANXA8 knockdown or overexpression in A549 cells, which confirmed the activation of the EGFR/Akt/mTOR signaling pathway by ANXA8. The present results provided evidence to support further investigation of the functional identification of ANXA8 in lung cancer cells in the future.

Intratumoral heterogeneity and clonal variability are among the central problems of clinical oncology, leading to resistance to therapy, relapse, and metastasis. High-throughput sequencing of the tumor exome makes it possible to investigate the subclonal tumor organization. Target panel, clinical exome, and complete exome sequencing data were compared in tumors with different mutational burden, acute myeloid leukemia (AML) in children and acral melanoma. Targeted sequencing of AML samples detected more than one potential driver mutation in the signaling pathway genes KIT, NRAS, KRAS, CBL, and FLT3 in one patient, reflecting the complex clonal structure of the tumor substrate. Clusters of mutant alleles corresponding to different populations of leukemic cells in a sample were isolated based on exome sequencing data from the same AML patients. A comparison of the mutation profile for a primary AML sample and samples obtained in remission and relapse made it possible to trace the dynamic changes in the clonal composition of the tumor. The subclonal tumor structure was investigated in an acral melanoma case as an example. Mutant alleles present in the sample with close frequencies were clustered using the SciClone and ClonEvol packages. The results were used to predict the intratumoral clonal composition and to assume a clonal evolution model, which described the changes in the clonal composition of the tumor during metastasis, including the appearance of new mutations that might be associated with further disease progression. The approach used in the work is suitable for identifying the mutations that cause the formation of new tumor clones, which may have a proliferative advantage, in particular, in conditions of antitumor therapy.

Inflammatory myofibroblastic tumors of the uterus (uIMT) are rare and difficult to diagnose neoplasms, since the morphological characteristics of this tumor are not specific and are found in other pathological changes. In addition, until recently, specific uIMT markers have not been identified and their diagnostic standards not defined. However, in recent years, there have been more and more studies aimed to identify characteristic morphological, immunohistochemical, and molecular genetic features for the differential diagnosis of uIMT. Recent papers studying uIMT indicate anaplastic lymphoma kinase (ALK) as a potentially reliable marker of uIMT. This communication describes a clinical case of uIMT in a 40-year-old woman who has been preoperatively diagnosed with a large subserous interstitial myomatous nodule. The final diagnosis was made, by analysing a combination of morphological and immunohistochemical signs. This clinical case with a literature review is indicated to consider ALK as a key criterion in the diagnosis of uIMT, as well as the relationship between subsequent treatment and the presence of ALK in the studied tissues.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate malignancy potential, which predominantly affects children and young adults. This paper describes two cases of AFH, as well as a review of literature during 1979 to 2021. It gives data on the epidemiology, clinical features, diagnosis, and genetic characteristics of AFH.

To evaluate the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas based on surgical material morphological and immunohistochemical data.

There are data about 6 cases of acute leukemia in children who have been diagnosed with COVID-19 infection 1-1,5 months before, or at the same time. In 5 patients lymphoblastic and in one monoblastic acute leukemia were diagnosed. The course of leukemia passed without any particular complications. Attention is drawn to the presence in 5 patients of either a clone with high hyperdiploidy, or the presence of an increased number of polyploid cells. At the same time, pulverization and fragmentation of chromosomes often observed during radiation, viral exposure, cancer and precancerous hyperplasia, were found. It is suggested that the mitosis disorder we identified in several cases of COVID-19, accompanied by polyploidy, pulverization and fragmentation of chromosomes, can be regarded as a "second hit " during development of childhood acute leukemia, or as an accelerator of the manifestation of an already existing process.

This review is devoted to the problem of anaplastic cerebral gliomas. The authors consider classification, neuroimaging of these tumors including comparison of magnetic resonance imaging and positron emission tomography data. Clinical manifestations of anaplastic gliomas, issues of their histological and molecular genetic classification are discussed. Moreover, the authors compare the data of neuroimaging and genetic examinations of tumors. Other issues are multicomponent treatment and prognosis in patients with anaplastic glioma of the brain.

Hepatocellular Carcinoma (HCC) is the fourth leading cause of cancer-related death in the World. Epidermal Growth Factor Receptor (EGFR) pathway plays an important role in HCC tumorigenesis. In the tumor microenvironment of HCC, the expression of EGF is aberrant. Here we describe the EGF-dependent regulation of URGCP gene in Human Hepatoma cancer cells (Hep3B). The effect of EGF cytokine on Hep3B proliferation was shown using MTT method. EGF-mediated URGCP expression was determined at mRNA and protein level with qRT-PCR analyses and Western blotting method, respectively. Different lengths of URGCP promoter constructs were transient transfected in to Hep3B cells and the basal promoter activities were determined in the presence of EGF. In addition, some pathway analyses were performed to find out the mechanism of EGF mediated up-regulation of the URGCP gene. In the presence of EGF, URGCP expression increases in concentration and time dependent manner. EGF mediated URGCP up-regulation might depend on a cis-acting element located between -344 and -482 positions in its promoter.

MicroRNAs epigenetically regulate physiological and pathological processes. Previously, we found that miR-204-5p is expressed at low levels in melanoma cells, and an increase in its level leads to a change in proliferation, migration, and invasion of these cancer cells. Now, using bioinformatics analysis, it has been shown that the target of miR-204-5p is FOXC1 transcription factor, which is implicated in carcinogenesis. Using the luciferase reporter assay, it was found that miR-204-5p suppresses expression of the FOXC1 gene by binding to its 3' non-coding region. Transfection of small interfering RNA (siRNA) targeting FOXC1 into melanoma cells caused a decrease in miR-204-5p levels, which is consistent with the generally accepted concept of feedback regulation of miRNA expression by target genes. According to the results of the MTT test and fluorescence microscopy, the proliferation level of melanoma cells under the influence of siRNA to FOXC1 decreased 72 h after transfection. Changes in the ratio of cells by cell cycle phase were analyzed using flow cytometry. Regulatory relationships between FOXC1 and miR-204-5p, and an inhibitory effect of FOXC1 knockdown on melanoma cell proliferation were revealed. Based on the results, it can be assumed that miR-204-5p regulates proliferation of melanoma cells by affecting FOXC1 expression.

Non-small cell lung cancer (NSCLC) is prevalent worldwide and has a high mortality rate. Even if mesenchymal stem cells (MSCs) are suggested as cancer treatment, the studies of their effects on NSCLC cells contradict each other, mainly due to utilization of two-dimensional (2D) culture system. Three-dimensional (3D) culture systems resemble tissue organization in vivo. Here we comprehensively explore the inhibitory effects of MSCs on NSCLC cells in a 3D culture system. We confirmed that the inhibitory effects of 3D-cultured MSCs (3D-MSCs) on the proliferation and migration of NSCLC cells are greater than that of the 2D-cultured MSCs. 3D-MSCs overexpress IL-24, which serve as the key factor enhancing antitumor effects of MSCs. In these cells, IL-24 affects p38 MAPK and CXCR4/AKT pathways. Overall, this study provides the support for use of MSCs in tumor.

Collagens are the main components of human tissues. Various regulatory factors and cytokines may influence expression levels for collagen-encoding genes, and, therefore, contrubite to some collagen-associated pathologies. In this study, we demonstrate regulatory effects of USF1 on expression of genes encoding fibrillar collagen types I, II, and III in osteoblastic Saos-2 and MG-63 cells. An ectopic expression of the human USF1 led to a decrease in both mRNA and protein expression levels of the collagen-encoding genes mentioned above. ADAMTS-3 is a proteinase primarily responsible for the amino-terminal cleavage of type I and type II collagen precursors. The ADAMTS-3 promoter region contains potential binding sites for USF1. Here we show that an overexpression of USF1 lead to a decrease in ADAMTS-3 mRNA and protein expression levels. In co-transfection studies, USF1 negatively regulated ADAMTS-3 promoter activity. Further, in EMSA studies, we showed that USF1 binds to the ADAMTS-3 promoter region. In conclusion, it seems that ADAMTS-3 and USF1 contribute to the regulation of collagen encoding genes in osteosarcoma.

Autophagy is an evolutionarily conserved cellular process in which components of the cytoplasm are delivered to lysosomes for degradation and has been proposed to play a role in imatinib resistance in chronic myeloid leukemia cells. Chronic myeloid leukemia is a clonal myeloproliferative disorder arising from the neoplastic transformation of the hematopoietic stem cell. We used a Bcr-Abl-independent and imatinib-resistant K562 subpopulation (K562-IR) that we generated earlier in our laboratory for this study. We showed that in the presence of imatinib autophagy was triggered via LC3I/II transformation, p62 protein expression and acidic vacuoles accumulation in tyrosine kinase inhibitor-sensitive K562 cells; whereas in the cell line K562-IR which is imatinib-resistant and Bcr-Abl independent, autophagy is not triggered. With ongoing research and trails to combine tyrosine kinase inhibitors with autophagy inhibitors, our results suggest a model of resistance in which treatment with a TKI inhibitor does not increase autophagy, basically because its presence does not cause cellular stress due to Bcr-Abl signaling not being required for survival.

Tumor-specific promoters and cis-regulatory genetic elements are used for transcriptional control of therapeutic transgene expression in cancer gene therapy. HRE (hypoxia response element) and ARE (anti-oxidant response elements) cis-regulatory elements are targets for HIF1 and Nrf2 transcriptional factors, respectively, and mediate activation of gene transcription in a response to hypoxia and oxidative stress, characteristic of most solid tumors. Due to these features HREs and AREs are used in genetic constructs for cancer gene therapy to provide tumor-specific therapeutic transgene expression or replication of oncolytic adenovi-ruses. In this work on the basis of the tumor-specific promoter hTERT we have constructed hybrid promoters carrying combinations of HRE and ARE. We showed that upon imitation of hypoxia in human lung cancer cell lines the activity of the hybrid promoter HRE-ARE-hTERT is substantially higher compared to promoters carrying only ARE or HRE. Using in vitro suicide cancer gene therapy with the CD: UPRT/5-FC (cytosine deaminase; uracil phosphoribosyl transferase/5-fluorocytosine) enzyme-prodrug system as a model we showed an enhancement of the cytotoxic effect on human lung cancer cells upon imitation of hypoxia when cytosine deaminase: uracil phosphoribosyl transferase was expressed under the control of the HRE-ARE-hTERT promoter compared to HRE-hTERT and ARE-hTERT promoters. The novel hybrid promoter HRE-ARE-hTERT could be used for transcriptional targeting of therapeutic transgene expression or oncolytic adenovirus replication upon development of novel anti-cancer gene therapeutics.

Recently, a wealth of data have been accumulating on the role of long non-coding RNAs (lncRNAs) in the fine-tuning of mRNA expression. Four new lncRNAs, namely, TMEM92-AS1, FAM222A-AS, TXLNB, and lnc-CCL28, were identified as differentially expressed in ovarian tumors using deep machine learning. The levels of lnc-CCL28 transcripts in both tumors and normal tissue samples were sufficient for further analysis by RT-PCR. In addition, the promising ovarian cancer biomarkers, lncRNAs LINC00152, NEAT 1 and SNHG17 were added to RT-PCR analysis. For the first time, an increase in the level of lnc-CCL28 and SNHG 17 lncRNAs was found in ovarian tumors, and the overexpression of LINC00152 and NEAT1 was confirmed. It seems that lnc-CCL28 is involved in carcinogenesis and, in particular, in ovarian cancer progression. Overexpression of LINC00152 and lnc-CCL28 was significantly associated with the later stages and metastasis.

Small SCP phosphatases CTDSP1, CTDSP2, and CTDSPL specifically dephosphorylate serine and threonine residues in protein molecules. The enzymes are involved in regulating activity of RNA polymerase II at the transition from transcription initiation to elongation, regulating expression of neuron-specific genes, and activating the key cell-cycle protein pRb at the G1/S boundary. In addition, the substrates of SCP phosphatases include SMAD transcription modulators; AKT1 protein kinase, which regulates the cell cycle, apoptosis, and angiogenesis; the TWIST1 and c-MYC transcription factors; Ras family proteins, which are involved in signaling pathways regulating the cell growth and apoptosis; CDCA3, which is associated with cell division; the cyclin-dependent kinase inhibitor p21; and the promyelocytic leukemia protein (PML), which is involved in regulation of the tumor suppressors p53, PTEN, and mTOR. Dysfunction or inactivation of SCP phosphatases leads to various diseases, including cancer. Recently the increase in interest to SCP phosphatases is due to their their tumor growth-inhibiting properties or role in the development of malignant tumors of various etiology and localization. The review discusses the properties of SCP phosphatases and their role in oncogenesis. Understanding the functions of SCP phosphatases and their regulatory mechanisms can be useful in searching for efficient targets for tumor therapy.

The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. However, the mechanisms leading to a change in its expression, the diagnostic or prognostic value of the receptor in BC are currently poorly understood. Here, we have evaluated the relative level of OXTR expression in BC samples (n=107), and also investigated the effect of estradiol on its expression in MCF-7 and MDA-MB-231 cells. The level of OXTR expression was significantly lower in breast tumor tissue than in normal tissue obtained from the same patient. The expression of OXTR was dependent on the status and expression of the estrogen receptor (ER): the level of OXTR mRNA was significantly lower in ER-negative BC samples compared to ER-positive BC samples. Moreover, OXTR expression was also lower in samples from patients with luminal subtype with a low value of ER expression (0-5 score according to the IHC assay, Allred scoring) compared with samples with high ER expression (6-8 score). In luminal BC, OXTR expression was associated with the HER2 expression level: the OXTR mRNA level was higher in tumors with a HER2 IHC score of 1+ as compared to cases with the HER2 expression score of 2+, 3+. We also showed that estradiol increased the level of OXTR mRNA in MCF-7 cells, but not in ER-negative MDA-MB-231 cells. These data indicate that changes in OXTR expression in BC tissues can be caused by increased ER expression. We found no association between OXTR and T or N stages and progesterone receptor expression.

LiFraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary disorder that is characterized by an increased risk for certain types of cancer, acute lymphoblastic leukemia (ALL), particularly. Germline TP53 mutations are associated with LFS. Genetic counseling and follow-up is essential for patients with LFS and their relatives. Special therapeutic approaches are needed for treatment of oncological disease in these patients. The article presents a series of clinical cases of patients with ALL and SLF, considers general issues of diagnosis and treatment of adult patients with this hereditary genetic syndrome.

To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years.

Gastric cancer is one of the leading causes of cancer morbidity and mortality worldwide. It is common practice to use two classification systems: the Lauren classification system and the WHO classification of tumors in the morphological study of gastric carcinomas. Since 2010, the WHO classifications have included the term "poorly cohesive carcinoma", which refers to all diffuse forms of gastric cancer, including signet ring cell carcinoma and other subtypes. Despite this, the term has not been widely used in the world community, and it is almost not found in Russian literature. Only recently, after the publication of the 5th edition of the WHO classification (2019), there have been review articles where the term is used, but its name can be translated into Russian in different ways: poor-, weak -, low-adhesive, discogesive. The paper analyzes the Pubmed and Elibrary databases in order to find out the frequency of using various designations for diffuse gastric carcinoma, justifies the use of the term «poorly cohesive carcinoma», and proposes a variant of the term interpretation in Russian.

Mutations in the C-KIT gene encoding type III receptor tyrosine kinase that regulates cellular processes, such as differentiation, survival, proliferation, migration, and apoptosis, are found in some neoplasms: gastrointestinal stromal tumor, mastocytosis, melanoma, breast carcinomas, myeloid leukemias, and a number of others. Tumors that exhibit these mutations are sensitive to therapy with tyrosine kinase inhibitors, which makes it necessary to correctly identify the mutation status by C-KIT in order to apply a personalized approach to therapy. This literature review shows that the type and localization of the C-KIT gene mutation are of crucial prognostic value and significance in choosing drugs for antitumor therapy, but traditional diagnostic methods fail to determine accurate mutation characteristics. Routine sequencing techniques focus on identifying the gene mutations associated with specific cellular processes, such as DNA damage and repair. The emergence of next-generation sequencing techniques has solved this problem, making it possible to fully analyze the genome of a malignant neoplasm, with constant screening for new mutations that appear as the tumor develops, affect the prognosis of the disease, and change its sensitivity to the antitumor therapy.