ULTRASOUND DIAGNOSTICS OF CERVICAL CHANGES WITH DIFFERENT LOCALIZATION OF THE CERVICITIS IN WOMEN WITH THE ECTOPY OF THE VAGINAL PORTION OF THE CERVIX.

The aim of the study was to improve the diagnosis of structural changes in all parts of the cervix depending on the preferential localization of the inflammatory process - in the ectocervix, endocervix, and also in the stroma in women with ectopia (pseudoerosis) of the vaginal part of the cervix. The study included women of predominantly early and middle reproductive age, as these women have inflammatory processes more often than in menopause. To perform the work, a transvaginal imaging method was used, which allowed us to see the smallest structures (up to 0.5-1.0 mm) of the cervix. We have previously developed a technique for visualizing the external part of the cervix and obtained a patent of Ukraine. The results of the ultrasound were compared with laboratory data, colposcopy and cervicoscopy. Traditionally, the diagnosis of cervicitis was made on the basis of clinical symptoms, smear results to determine the presence and type of pathogen. Endoscopic methods allowed visualization of only the mucous membrane of the cervical canal and external part of the cervix. The deep layers of the ectocervix, endocervix and cervical stroma can only be visualized using high-frequency ultrasound in a transvaginal way. According to the results of the study, it was possible to determine the preferential localization of the inflammatory process, to determine the nature of changes in different layers of the cervix. These changes were expressed in the presence of calcifications and cystic cavities of various sizes (1-6 mm), an increase or decrease in echogenicity, the degree of heterogeneity of the structure of the ecto-, endocervix and stroma.

Potential value of high-throughput single-cell DNA sequencing of Juvenile myelomonocytic leukemia: report of two cases.

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 secondary acute myeloid leukemia (sAML). The methods of single-cell DNA sequencing (scDNA-seq) enable overcoming limitations of bulk NGS and exploring genetic heterogeneity at the level of individual cells, which can help in a better understanding of the mechanisms leading to JMML progression and provide an opportunity to evaluate the response of leukemia to therapy. In the present work, we applied a two-step droplet microfluidics approach to detect DNA alterations among thousands of single cells and to analyze clonal dynamics in two JMML patients with sAML transformation before and after hematopoietic stem cell transplantation (HSCT). At the time of diagnosis both of our patients harbored only "canonical" mutations in the RAS signaling pathway genes detected by targeted DNA sequencing. Analysis of samples from the time of transformation JMML to sAML revealed additional genetic events that are potential drivers for disease progression in both patients. ScDNA-seq was able to measure of chimerism level and detect a residual tumor clone in the second patient after HSCT (sensitivity of less than 0.1% tumor cells). The data obtained demonstrate the value of scDNA-seq to assess the clonal evolution of JMML to sAML, response to therapy and engraftment monitoring.

Early-onset oral cancer as a clinical entity: aetiology and pathogenesis.

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 review summarizes the available information regarding clinicopathological features, extrinsic and intrinsic aetiological factors, and the molecular and immune landscape of early-onset OSCC. This cancer shows high recurrence rates and is not associated with the aetiological factors specific to adult-onset OSCC. Young adults with OSCC are not infected with human papillomavirus and rarely consume alcohol or tobacco, but more frequently use smokeless tobacco. Data from single studies indicate the hereditary nature of early-onset OSCC: the KIR2DL1+-HLA-C2+ genotype and MMP-1 2 G allele are frequently detected in young patients. Early-onset OSCC shows specific genetic, epigenetic, transcriptomic, and proteomic changes. The tumour microenvironment in early-onset OSCC is tolerogenic rather than immunogenic. All of the data suggest that OSCC in young patients is a separate clinical entity with a specific aetiology and pathogenesis. Further studies are needed to reveal the causes and molecular targets of early-onset OSCC for the development of preventive and therapeutic strategies.

Cytostatic cancer therapy modulates monocyte-macrophage cell functions: how it impacts on treatment outcomes.

Macrophages are important effectors of innate immunity and the key component of the tumor microenvironment strongly influencing cancer disease outcome and efficiency of cancer therapy. Moreover, recent data have shown that monocytes as macrophage precursors can impact on tumor ability to progression. It's well known that although tumor-associated macrophages consist of diverse populations, in general, they have tumor-supporting activity. To change tumor-supporting state of tumor-associated macrophages toward tumor-inhibiting mode is one of prospective aims of modern cancer immunotherapy. Cytostatics seems to be possible tools to achieve this aim, because recently it has been shown that chemo- and radiotherapy possess immunomodulatory effects. Most of the findings are related to lymphocytes - T-lymphocytes and NK-cells, but not to monocyte/macrophage lineage. In the review, we have analyzed how cytostatic drugs influence the properties of monocyte/macrophage lineage cells to prospect using of chemotherapy to enhance their antitumor activity.

[Soluble high molecular weight derivatives of pancreatic inhibitors. Kinetic-thermodynamic studies of inhibitors linked to differently charged matrices]. / Rastvorimye vysokomolekuliarnye proizvodnye pankreaticheskogo ingibitora. Kinetiko-termodinamicheskoe izuchenie ingibitora sviazannogo s matritsamil imeiushchimi razlichnyi.

The effects of electrostatic charge of the matrix on the pH-dependence of interactions of commercial trypsin with preparations of pancreatic inhibitor modified by soluble polysaccharide coupling were studied. It was shown that the rate constants of trypsin association with native and modified pancreatic inhibitor preparations as well as the rate constants of dissociation of their complexes and, consequently, the inhibition constants are identical. The invariability of the rate constants for the association reaction after the increase in the molecular weight of pancreatic inhibitor may be probably accounted for by the fact that the limiting step of a stable trypsin-inhibitor complex formation is not controlled by diffusion. Thermal denaturation of pancreatic inhibitor preparations modified by binding to polysaccharides (pH 4.7--8.0, 97 degrees C) suggests an essential role of the negative charge of matrix in stabilization of the protein inhibitor globule.