Intravenous leiomyomatosis is a rare disease from a group of tumors with the indefinite grading potential. The paper describes two cases of intravenous leiomyomatosis with its detailed morphological pattern, molecular genetic findings, and a brief literature review. Losses of heterozygosity of microsatellite repeats thatwere located on chromosome 10 in 10q22.1 and common in uterine leiomyosarcomas were found in both cases. Investigations of the morphological and biological characteristics of leimyomatosis are important to clarify the key molecular mechanisms underlying the development of this nosological entity and to determine etiopathogenetic relationships between intravenous leiomyomatosis and other uterine smooth muscle neoplasms.

Predisposition to tumors is often determined by how effectively the genotype of an individual forms an immune defense. An important factor of such protection is macrophage NO. We assumed that the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. The content of NO in the tumor changed by ITU, inhibitor of iNOS, c-PTIO, traps and SNP, donor NO. Production of macrophage NO were evaluated by nitrites in the culture media. iNOS was assessed using the Western blot analysis. Phenotype of macrophages was assessed using cytometry for CD labels. Life span of mice C57BL/6N with Ehrlich tumor was 25% greater than that of the C57BL/6J. Reducing the content of NO in the tumor reduced life expectancy of high-resistance to tumor subline C57BL/6N at 23%. Increase of NO increased life expectancy of low-resistance subline C57BL/6J at 26%. Macrophages of C57BL/6N were 1.5 times higher contents of iNOS and NO production, as compared with macrophages of C57BL/6J. CD phenotype markers determined the macrophage phenotype C57BL/6N as M1 and C57BL/6J mice macrophage phenotype as M2. Thus, the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. C57BL/6J, unlike C57BL/6N does not synthesize NNT (nicotinamide nucleotide transhydrogenase) and have differences in the single nucleotide polymorphism (SNP). The important role of NO in the resistance to Carcinoma, NNT and SNP deserve attention in the development of new methods of antitumor therapy.

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children of first year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

Most human tumors, including cervical cancer, are characterized by telomerase activation (cell proliferation activation enzyme). Such activation is implemented in the elongation of the terminal segments (telomeres) of the telomerase chromosome. The gene of the enzyme is RNA-encoded, the RNA in tumors being observed in a few isoforms. The hTERT RNA role in cell activation and control was simulated using cervical cancer, as well as its pretumoral states (CIN), as a model object. The goal of this work was to clone of the human hTERT isoforms (normal, α-, β-, and α+β-splice-variants). The genetic constructions containing normal hTERT sequence, α- and β-deletion variants based on the lentivirus vector pR780 were obtained. The α- and β-deletion variants were not obtained in this variant because of methodological problems. In further research, we plan to implement splice-variants of hTERT in eukaryotic human cells.

The histological diagnosis of malignant brain tumors in children is a complex process. In some cases, glioblastoma, primitive neuroectodermal tumor of the central nervous system, and atypical teratoid/rhabdoid tumor have a histological type similar to that of small blue round cell malignant tumor. Despite the similar histology, biological properties and approaches to treatment, these neoplasms are completely different and require their own treatment protocols. We retrospectively reviewed the most malignant types of childhood tumors and analyzed our own experience to propose a diagnostic algorithm for intracerebral small blue round cell malignant tumors in children based on the use of immunohistochemistry and fluorescence in situ hybridization.

Significant changes occurred in drug therapy for disseminated melanoma during the last 5 years. New classes of pharmaceuticals appeared in daily clinical practice: inhibitors of MAPK pathway components (BRAF inhibitors vemurafenib and dabrafenib, MEK--inhibitors trametinib and cobimetinib) and immune checkpoint inhibitors that modulate immunologic synapse activity. This article presents information about MAPK pathway inhibitors, their mechanism of action and clinical trials experience including specific related adverse events. Relation of the therapies describes to the other methods in the field are also described. Algorithm of personalized use of current antineoplastic drugs in melanoma is presented. Modern therapeutic approaches in melanoma provide profound and long lasting effects and can even cure some patients. Rational consecutive and combined application of current methods, proper diagnostic and management of related AE can prolong life span of patients and meaningfully increase their quality of life.

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

Discovery of activating EGFR mutations led to dramatic modification of treatment schemes for nonsquamous lung cancer. 70 patients with activating EGFR mutations were treated by gefitinib being either a part of prospective phase II trial (n = 25) or, subsequently, subjected to routine clinical management (n = 45). Objective response rate approached to 32.7%. Median time to disease progression was 14 months, and median overall survival was 26.1 months. Subgroup analysis revealed statistically longer time to disease progression (p < 0,0001) and overall survival (p = 0,001) in latter vs. former group, despite the lower rate of objective response (22% vs 48%). Possible explanations include more relaxed standards for routine gefitinib use, i.e. inclusion of the patients with non-measurable tumor lumps, continuation of gefitinib uptake upon slow disease progression, and increasing availability and quality of radiosurgery for brain metastases.

To clarify the association between microsomal epoxide hydrolase gene (EPHX1) Tyr113His polymorphism and hepatocellular carcinoma (HCC) risk, a meta-analysis was performed. Overall, EPHX1 Tyr113His polymorphism was associated with increased risk of HCC. Subgroup analyses by status of Hardy-Weinberg equilibrium (HWE) in controls further confirmed this association. Through a literature search, 119 relevant records were identified, and 17 individual case-control studies from 13 publications were finally included, involving a total of 1,480 HCC cases and 2,564 controls. In subgroup analyses, increased associations were found in Asians, Caucasians, hepatitis B virus (HBV)- dominant areas, hepatitis C virus (HCV)-dominant areas, high-rate areas of HCC, and medium-rate areas of HCC, but not in Africans and low-rate areas of HCC, respectively. This meta-analysis suggests that EPHX1 Tyr113His polymorphism contributes to HCC risk.

The transcriptomic profiles of human breast cancer cell lines MCF-7 and MDA-MB-435 were investigated using the next-generation RNA sequencing (RNA-Seq). The DESeq package was used to screen the differentially expressed transcripts. A total of 229 genes with a significantly differential expression in MDA-MB-435 cells as compared with MCF-7 cells were obtained. Annotation of the biological functions of these genes through the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7 demonstrated that the 229 differentially expressed genes were mainly implicated in the biological functions related to cell adhesion and motion, antigen processing and presentation (via MHC class II), hormone response, extracellular structure organization, tissue remodeling, and cell proliferation regulation. Analysis of the individual genes demonstrated that MDA-MB-435 cells exhibited a higher tendency to metastasis and antigen processing and presentation, and lower ability to hormone response. Twenty most abundant transcripts in MDA-MB-435 cells, such as VIM, TNC, and CD74, represent its high potential for metastasis. Besides the genes previously reported to be involved in tumor metastasis and development, genes newly identified in this study could provide new clues for the diagnosis and prognosis of aggressive breast cancers.

Review is devoted to the analysis of changes of the extracellular DNA (excDNA) in pathological conditions involving the process of apoptosis, and the possibility of using of excDNA in the diagnosis and evaluation of course of various diseases. Apoptosis is the main mechanism of the appearance of the DNA in the circulation. ExcDNA found in the norm, its function is considered to be the part of the immune response. The excDNA content increases substantially during the induction of apoptosis. Dynamics of increase of excDNA content in stroke allows to diagnose the form of stroke and massiveness of destruction of brain tissue. Reduced content of excDNA is associated with the inhibition of apoptosis, it was shown that under such conditions there is a change of composition of excDNA. Investigation of excDNA character changes in the progression and treatment of cancer substantiates the possibility of early assessment the effectiveness of treatment. It is experimentally shown the immunosuppressive action of excDNA of tumor and its transforming effect on the cells. Ionizing radiation is an examples that demonstrated the association of induction of apoptosis and the release of excDNA. It is characterize some of the genome sequences of excDNA. Created on the basis of excDNA study tests of minimally invasive diagnostics are potentially useful in oncology and other areas of medicine. The study of tandem repeats, which are absent in the assembled genome, but there is a part of excDNA, will create tests for the diagnosis of cancer in the early stages.

to assess mutational events in exons 5, 7, and 8 of the p53 gene and to reveal mutant p53 protein in verified cases of morphologically altered (proliferative and precancerous changes, lung cancer) and histologically unaltered, lung tissues in workers exposed to occupational radiation.

to study HER2 protein and HER2 gene, their heterogeneity in non-small cell lung cancer.

One of the important questions in understanding the mechanisms of carcinogenesis induced with foreign body (or plastic carcinogenesis), is a question about normal progenitor cells in sarcomas (FB sarcomas) appearing in close proximity to the plastic plate implanted under the skin of an experimental animal. There is an assumption in literature that progenitor cells in FB sarcomas originate from vascular endothelium cells feeding a connective tissue capsule that forms around foreign body. In our research, we studied mRNA expression of one of the endothelial cell markers--receptor VEGFR2/FIk1--and growth factor VEGF-A, which interacts with it, in precancerous cells of FB sarcomas in mice. In examined cells, mRNA expression of VEGF-A was found while mRNA expression of VEGFR2/FIk1 was absent. In light of this and formerly established properties of progenitor cells in FB sarcomas, possibilities of the origin of these sarcomas from endothelial cells, pericytes, and pluripotent mesenchymal stem cells are being discussed.

This paper studies the effect of plant peptides of thionine Ns-W2 extracted from seeds of fennel flower (Nigella sativa) and β-purothionine from wheat germs (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the expression of several genes involved in the.control of cellular homeostasis, processes of carcinogenesis, and radiation response in human rhabdomyosarcoma cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of these agents acted as antimutagens-anticarcinogens, reducing the expression of genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G-protein genes) in a tumor cell. A pronounced reduction in the mRNA level of these genes was caused by thionine Ns-W2, and the least effect was demonstrated by β-purothionine. Antimutagens had very little effect on the mRNA levels of the several studied genes in normal blood cells.

Recent studies have suggested that contactin-1 has a key role in cancer cell proliferation and migration, however the detailed mechanism of this process is still unclear. Here, human gastric cancer cell line MKN45 was employed. It was found that under hypoxia conditions contactin-1 mRNA and protein levels were both up-regulated by HIF-1alpha expression. Furthermore, although hypoxia increased the migration rate of MKN45 cells, contactin-1 (CNTN1) shRNA reversed this process. Meanwhile, RhoA V14 and RhoA V14N19 mutation constructs were employed, and it was found that constitutively active form of RhoA reversed the cell migration suppression induced by contactin-1 knockdown, while dominant-negative form of RhoA blocked hypoxia induced hypermigration. Apart from this, contactin-1 displayed the ability to phosphorylate the RhoA activator p115 RhoGEF. Thus, under hypoxia conditions, elevated HIF-1alpha seems to up-regulate contactin-1 expression and by this activate RhoA and facilitate migration of cancer cells.

The major methods of microRNA extraction from different biological fluids (particularly, serum and plasma), approaches to the analysis of microRNA concentration and composition, normalization methods used in data analysis are outlined in the review. The advantages and disadvantages of the described methodological approaches are being highlighted. Special attention is given to microRNAs, circulating in blood, which could be used as the markers for minimally invasive lung cancer diagnostics, prediction of antitumor treatment efficiency and disease prognosis. Prospects and limitations arising from the evaluation of clinical significance of microRNAs as the potential tumor markers, and emerging as roles of various microRNAs in the pathogenesis of lung cancer become known, are discussed.

MicroRNAs (miRNA) are small noncoding RNAs that are critical regulators of gene function. In the recent years, miRNAs have been increasingly noted for their capacity to regulate key malignant properties of tumor cells. MicroRNA-128 (miR-128) is a brain-enriched miRNA that is normally involved in the development of the nervous system and in the maintenance of neural physiological functions. In tumorcells, miR-128 expression is dysregulated through a variety of genetic and epigenetic events. Dysregulation: of miR-128 has profound effects on tumorigenesis and maintenance of tumor cells through alterations in cellular proliferation, differentiation, metabolism, and apoptosis. This article will review the latest advances in our understanding of miR-128, specifically in the context of clinical and fundamental cancer biology. Further characterization of miR-128 will likely identify its new roles in cancer biology. The use of miR-128 as a diagnostic and/or therapeutic tool may result in improvements in diagnosis, prognosis, and treatment of numerous cancers.

The review of the literature about the results of the study of the role of 4a/b VNTR-polymorphism of eNOS in pathophysiology of various states of the body. It is shown that the data are ambiguous and sometimes contradictory. The study of the contribution of candidate genes to the implementation of multifactorial diseases can increase the accuracy of prediction of the set of risk factors, early diagnosis facilitate and sufficient therapy of multifactorial diseases.

Scorpion venom is a complex multicomponent mixture of biologically active substances, some of which possess very interesting properties and are used in quite unexpected fields. The family of chlorotoxin (CTX)-like peptides serves a good example. These toxins exhibit insecticidal activity, however, their molecular mechanism of action on insect organism remains elusive. Nevertheless, CTX-like peptides attracted considerable research effort due to their ability to specifically interact with cells of brain tumors, i.e. gliomas. In the future these compounds may considerably aid anticancer therapy. This review summarizes the results obtained during the past 40 years of CTX-like peptides investigation. Both biological function aspects and the applied field related to gliomas are considered.