[Amplifiation of the c-MYC gene in acinar prostate adenocarcinoma. Morphogenic comparisons]. / Amplifikatsiya gena c-MYC pri atsinarnoi adenokartsinome prostaty. Morfogeneticheskie sopostavleniya.

OBJECTIVE: The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor. MATERIAL AND METHODS: The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe. RESULTS: In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05). CONCLUSION: Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.

Accumulation of ß-Amyloid Leads to a Decrease in Lynx1 and Lypd6B Expression in the Hippocampus and Increased Expression of Proinflammatory Cytokines in the Hippocampus and Blood Serum.

Alzheimer's disease is a rapidly progressive neurodegenerative disease, the development of which is associated with the accumulation of ß-amyloid oligomers, dysfunction of the α7-nAChR nicotinic acetylcholine receptor, and activation of inflammation. Previously, we showed that the neuromodulator Lynx1, which belongs to the Ly6/uPAR family, competes with ß-amyloid(1-42) for binding to α7-nAChR. In this work, we studied the expression and localization of Ly6/uPAR family proteins in the hippocampus of 2xTg-AD transgenic mice that model AD and demonstrate increased amyloidosis in the brain. Using real-time PCR, we showed a decrease in the expression of the genes encoding Lynx1, Lypd6b, and the postsynaptic marker PSD95, as well as an increase in the expression of the TNFα gene in the hippocampus of 2xTg-AD mice. Histochemical analysis showed that, in the hippocampus of 2xTg-AD mice, Lynx1 does not colocalize with α7-nAChR, which can lead to the development of pathology when the receptor interacts with oligomeric ß-amyloid. In addition, in 2xTg-AD mice, activation of systemic inflammation was shown, which manifests itself in a decrease in the serum level of SLURP-1, a Ly6/uPAR family protein capable of regulating inflammatory processes, as well as in an increase in the content of proinflammatory cytokines TNFα and TNFß. Thus, α7-nAChR dysfunction and maintenance of the inflammatory microenvironment in the brain in Alzheimer's disease may be associated with a decrease in the expression of Ly6/uPAR family proteins that regulate α7-nAChR activity and inflammation.

Extracellular Vesicles Derived from Metastatic Melanoma Cells Transfer α7-nAChR mRNA, Thus Increasing the Surface Expression of the Receptor and Stimulating the Growth of Normal Keratinocytes.

We have previously shown that extracellular vesicles secreted by metastatic melanoma cells stimulate the growth, migration, and stemness of normal keratinocytes. This study showed for the first time that extracellular vesicles secreted by the metastatic melanoma cell lines mel H, mel Kor, and mel P contain, both at the mRNA and protein levels, the α7-type nicotinic acetylcholine receptor (α7-nAChR), which is involved in the regulation of the oncogenic signaling pathways in epithelial cells. Incubation with the vesicles secreted by mel H cells and containing the highest amount of mRNA coding α7-nAChR increased the surface expression of α7-nAChR in normal Het-1A keratinocytes and stimulated their growth. Meanwhile, both of these effects disappeared in the presence of α-bungarotoxin, an α7-nAChR inhibitor. A bioinformatic analysis revealed a correlation between the increased expression of the CHRNA7 gene coding α7-nAChR in patients with metastatic melanoma and a poor survival prognosis. Therefore, extracellular vesicles derived from metastatic melanoma cells can transfer mRNA coding α7-nAChR, thus enhancing the surface expression of this receptor and stimulating the growth of normal keratinocytes. Targeting of α7-nAChR may become a new strategy for controlling the malignant transformation of keratinocytes.

The GWAS-MAP|ovis platform for aggregation and analysis of genome-wide association study results in sheep.

In recent years, the number of genome-wide association studies (GWAS) carried out for various economically important animal traits has been increasing. GWAS discoveries provide summary statistics that can be used both for targeted marker-oriented selection and for studying the genetic control of economically important traits of farm animals. In contrast to research in human genetics, GWAS on farm animals often does not meet generally accepted standards (availability of information about effect and reference alleles, the size and direction of the effect, etc.). This greatly complicates the use of GWAS results for breeding needs. Within the framework of human genetics, there are several technological solutions for researching the harmonized results of GWAS, including one of the largest, the GWAS-MAP platform. For other types of living organisms, including economically important agricultural animals, there are no similar solutions. To our knowledge, no similar solution has been proposed to date for any of the species of economically important animals. As part of this work, we focused on creating a platform similar to GWAS-MAP for working with the results of GWAS of sheep, since sheep breeding is one of the most important branches of agriculture. By analogy with the GWAS-MAP platform for storing, unifying and analyzing human GWAS, we have created the GWAS-MAP|ovis platform. The platform currently contains information on more than 34 million associations between genomic sequence variants and traits of meat production in sheep. The platform can also be used to conduct colocalization analysis, a method that allows one to determine whether the association of a particular locus with two different traits is the result of pleiotropy or whether these traits are associated with different variants that are in linkage disequilibrium. This platform will be useful for breeders to select promising markers for breeding, as well as to obtain information for the introduction of genomic breeding and for scientists to replicate the results obtained.

[Rare kidney tumor - thyroid-like follicular carcinoma]. / Redkaya opukhol' pochki ­ tireoidopodobnaya follikulyarnaya kartsinoma.

The literature review provides an analysis of a rare malignant tumor of the kidney: thyroid-like follicular carcinoma of the kidney (TLFCK). In morphology, this tumor is extremely similar to thyroid follicular carcinoma, but the immunophenotype of tumor cells is different. TLFCK has an indolent clinical course, rarely metastasizes, and even the development of metastases does not mean an unfavorable prognosis for the patient. The literature review presents the features of the clinical course of the disease, macroscopic, microscopic, immunohistochemical characteristics of the tumor and typical cytogenetic breakdowns. Particular attention is paid to the issues of differential diagnosis of the tumor with other pathological processes that may microscopically resemble TLFCK.

[Thyroid-like follicular carcinoma of the kidney]. / Tireoidopodobnaya follikulyarnaya kartsinoma pochki.

Thyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare histological variant of renal cell carcinoma, not yet included in the WHO list of tumors. This tumor has a characteristic morphological structure strikingly resembling follicular carcinoma of the thyroid gland, but differing from itby the immunophenotype of tumor cells. TLFCK is characterized by an indolent clinical course, rarely metastases, and even the presence of metastases does not lead to a worsening of the prognosis for the patient. Described a case of TLFCK diagnosed in a 38-year-old patient, observed clinically for 8 years, without metastases during this time, and removed by focal kidney resection. The paper presents the macroscopic and microscopic characteristics of the tumor, immunohistochemical profile, and discusses the issues of differential diagnosis.

[What do we Mean by "Ideal" Blood Pressure Control?]

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.

A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

The phase composition, morphology and compressibility of graphene-zirconia composite nanostructured powder.

Nanostructured composite particles of nano- and submicron sizes were synthesized by a combination of sol-gel and sonochemical techniques. Their graphene content was 0.8-0.9 wt%. These layered particles consisted of graphene sheets in which zirconia nanocrystals were discretely incorporated. The synthesized powders were characterized using XRD, TEM, HRTEM, diffusion aerosol spectrometry and elemental analysis. A comparison of the compressibility modulus, limit values of linear section deformation and compressibility factor shows that the compressibility of the composite is difficult to achieve compared to that of pure zirconia, apparently, due to the low elasticity of graphene sheets.

Effect of iron oxide nanoparticles on fibrin gel formation and its fractal dimension.

In this paper, we studied the influence of nonmagnetic iron oxide nanoparticles on fibrin gel formation and its structure using dynamic light scattering. The surface of nanoparticles produced by a new method in acoustoplasma discharge with cavitation has specific morphology and accelerates the rate of fibrin gel formation, i.e., activates the enzyme thrombin. We studied changes in the form of autocorrelation functions of the scattered light intensity for fibrinogen-thrombin samples with different thrombin concentrations as well as the nanoparticles addition. Appearance of the power-law term in the function was an indicator of gel formation in the sample. Application of Martin's theory allows estimating the exponent φ of power-law function and the contribution of the diffusive mode of protofibrils. We found that an increase in thrombin concentration or its activation with iron oxide nanoparticles leads to decreasing contribution of the diffusive mode, and increasing contribution of the exponent of power-law function. The values of fractal dimension Df calculated using Muthukumar's theory are 1.61 ± 0.13 and 1.69 ± 1.11 for samples with low and high concentrations of thrombin respectively and 1.77 ± 0.08 for the sample with thrombin activated by nanoparticles. Such an increase in fractal dimension shows an increase in the complexity of the fibrin gel structure (or density).

Biotechnological wound dressings based on bacterial cellulose and degradable copolymer P(3HB/4HB).

Hybrid wound dressings have been constructed using two biomaterials: bacterial cellulose (BC) and copolymer of 3-hydroxybutyric and 4-hydroxybutyric acids [P(3HB/4HB)] - a biodegradable polymer of microbial origin. Some of the experimental membranes were loaded with drugs promoting wound healing and epidermal cells differentiated from multipotent adipose-derived mesenchymal stem cells. A study has been carried out to investigate the structure and physical/mechanical properties of the membranes. The in vitro study showed that the most effective scaffolds for growing fibroblasts were composite BC/P(3HB/4HB) films loaded with actovegin. Two types of the experimental biotechnological wound dressings - BC/P(3HB/4HB)/actovegin and BC/P(3HB/4HB)/fibroblasts - were tested in vivo, on laboratory animals with model third-degree skin burns. Wound planimetry, histological examination, and biochemical and molecular methods of detecting factors of angiogenesis, inflammation, type I collagen, and keratin 10 and 14 were used to monitor wound healing. Experimental wound dressings promoted healing more effectively than VoskoPran - a commercial wound dressing.

[Predictors of hepatic insufficiency in obstructive jaundice]. / Prediktory pechenochnoi nedostatochnosti pri mekhanicheskoi zheltukhe.

AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice. MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency. RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%. CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.

[The study of effectiveness of polyhydroxyalkanoates based biodegradable stents in ureteropelvic segment pyeloplasty].

INTRODUCTION: Among urologic diseases, ureteropelvic segment stenosis with hydronephrosis is a common indication for instrumental or surgical correction. The restriction of urine flow with dilatation proximal to obstruction develops in 6.5-37% of cases at different times after the ureteral reconstruction. All this urges to develop and improve stents and search for effective ways to place stents and control their function. AIM: To investigate the effectiveness of polyhydroxyalkanoates based biodegradable stent compared with a commercial analogue in upper urinary tract drainage after ureteropelvic segment pyeloplasty. MATERIALS AND METHODS: Morphological and functional changes in the stented ureter were investigated in 45 male rabbits of "Soviet chinchilla" breed weighing 4550-5200 g that underwent stenting of ureteropelvic segment (UPS). The study used polymeric stents based on poly-3-hydroxybutyrate, poly-4-gidroksibutirotom P (3GB/4GB) and a mixture of poly-3-hydroxybutyrate with polycaprolactone II (3GB)/PCL with the inclusion of PCL 75%; the control material was polyurethane stents. Morphologic evaluation was conducted on ureteral fragments and UPSs in the area of the stent placement at 7, 14 and 28 days after operation. RESULTS: Throughout the experiment, excretory urography and spiral tomography in experimental groups showed no changes in the pelvicalyceal system after placing polymeric stents. The morphologic examination in the experimental group at day 28 after surgery revealed preserved longitudinal folding of ureteral mucosa and absence of muscle hypertrophy. Transitional epithelium had no signs of atrophy and desquamation, its mean thickness was 112.4+/-8.5 mm, whereas in the control group a productive inflammation resulting in sclerosis was found to develop. CONCLUSIONS: We conducted a comparative study of morphologic and functional changes in rabbit ureters after stenting using polyurethane stents (control group) and polymeric stents made of poly-3-hydroxybutyrate, poly-4-hydroxybutyrate II (3GB /4GB) and a mixture of poly-3-hydroxybutyrate with polycaprolactone II (3Gb)/PCL (experimental group). Despite the difference in physical and mechanical properties of biodegradable PGA-based stents, the tissue response to both types of stent was comparable. Ureteral wall preserved longitudinal folds, there was no muscle layer hypertrophy, and mucous membrane had smooth contours with a uniform thickness of the transitional epithelium, whereas in the control group a productive inflammation resulting in sclerosis was found to develop.

Porous 3D implants of degradable poly-3-hydroxybutyrate used to enhance regeneration of rat cranial defect.

The study describes preparation and testing of porous 3D implants of natural degradable polymer of 3-hydroxybutyric acid P(3HB) for regeneration of bone tissue defects. The ability of the P(3HB) implants to favor attachment and facilitate proliferation and directed differentiation of mesenchymal stem cells (MSCs) was studied in the culture of MSCs isolated from bone marrow and adipose tissue. Tissue-engineered hybrid systems (grafts) constructed using P(3HB) and P(3HB) in combination with osteoblasts were used in experiments on laboratory animals (n = 48) with bone defect model. The defect model (5 mm in diameter) was created in the rat parietal bone, and filling of the defect by the new bone tissue was monitored in the groups of animals with P(3HB) implants, with commercial material, and without implants (negative control). Computed tomography (CT) and histologic examination showed that after 120 days, in the group with the osteoblast-seeded P(3HB) implants, the defect was completely closed; in the group with the cell-free P(3HB) implants, the remaining defect was no more than 10% of the initial one (0.5 mm); in both the negative and positive controls, the size of the defect was about 1.0-1.2 mm. These results suggest that P(3HB) has good potential as osteoplastic material for reconstructive osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 566-577, 2017.

Formation of Boron-Carbon Nanosheets and Bilayers in Boron-Doped Diamond: Origin of Metallicity and Superconductivity.

The insufficient data on a structure of the boron-doped diamond (BDD) has frustrated efforts to fully understand the fascinating electronic properties of this material and how they evolve with doping. We have employed X-ray diffraction and Raman scattering for detailed study of the large-sized BDD single crystals. We demonstrate a formation of boron-carbon (B-C) nanosheets and bilayers in BDD with increasing boron concentration. An incorporation of two boron atoms in the diamond unit cell plays a key role for the B-C nanosheets and bilayer formation. Evidence for these B-C bilayers which are parallel to {111} planes is provided by the observation of high-order, super-lattice reflections in X-ray diffraction and Laue patterns. B-C nanosheets and bilayers minimize the strain energy and affect the electronic structure of BDD. A new shallow acceptor level associated with B-C nanosheets at ~37 meV and the spin-orbit splitting of the valence band of ~6 meV are observed in electronic Raman scattering. We identified that the superconducting transitions occur in the (111) BDD surfaces only. We believe that the origin of Mott and superconducting transitions is associated with the two-dimensional (2D) misfit layer structure of BDD. A model for the BDD crystal structure, based on X-ray and Raman data, is proposed and confirmed by density functional theoretical calculation.

[EFFECT OF ANTI-CANCER DRUG DOXORUBICINE ON CYTOMEGALOVIRUS INFECTED HUMAN FIBROBLASTS].

The anticancer antibiotic doxorubicine (DOX) is highly toxic and induces functional complications in vital organs. The effect of DOX on normal cells has not been examined in sufficient detail, and the search for compounds reducing DOX toxicity did not lead to success so far. It has been suggested that DOX induces death of cancer cells via p53-dependent apoptosis, however, the information regarding the role of p73 protein, a member of p53 tumor suppressor family, is scanty. Cytomegalovirus (CMV) induces an antiapoptosis program that allows its replication until death of the target cell. Our objectives were to examine the effect of DOX on normal cells (human fibroblasts), analyze the ability of CMV-induced antiapoptosis program to reduce DOX toxicity, and to evaluate the involvement of p73 protein and its isoforms in the regulation of death of CMV-infected and DOX-treated cells. Within a 24-h time period DOX caused death of about 70% human embryonic lung fibroblasts (HELF) in cell culture, this parameter decreased significantly in CMV-infected DOX-treated HELF cells. TUNEL has shown that the number of cells with DNA fragmentation decreases from 5.2% under the effect of DOX to 3.2% (P < 0.05) after combined CMV-DOX treatment. Analysis of mitotic figures revealed that DOX causes accumulation of mitotic cells, which was not observed in CMV-infected DOX-treated cells. PCR analysis of mRNA of two p73 protein isoforms (TAp73 and dNp73) has shown that in uninfected cells the expression of TAp73 isoform was low, while in CMV-infected cells level of TAp73 was significant and expression of dNp73 was demonstrated for the first time. Expression of TAp73 associated with lack of mitosis block. The activation of caspases 8, 9 and 3 in CMV-infected cells was registered but cell death was not, however, as massive as that caused by DOX. From these findings it can be concluded that CMV attenuates DOX-related damage to normal cells. It can be suggested that induction of TAp73 and dNp73 isoforms provides conditions for reduction of DOX effect which leads to DNA damage and death of normal cells.

Phenotypic and phylogenetic segregation of Alternaria infectoria from small-spored Alternaria species isolated from wheat in Germany and Russia.

AIMS: To identify the taxonomic differences between phytopathogenic small-spored Alternaria strains isolated from wheat kernels in Germany and Russia by a polyphasic approach. METHODS AND RESULTS: Ninety-five Alternaria (A.) strains were characterized by their colony colour, their three-dimensional sporulation patterns, mycotoxin production and phylogenetic relationships based on sequence variation in translation elongation factor 1-α (TEF1-α). The examination of toxin profiles and the phylogenetic features via TEF1-α resulted in two distinct clusters, in each case containing Alternaria infectoria isolates (92 and 96% respectively) in the first and the Alternaria alternata, Alternaria arborescens and Alternaria tenuissima isolates (77 and 79% respectively) in the other combined cluster. The production of Alternariol, Altertoxin and Altenuene has not been reported previously in the A. infectoria species group. The isolates from Germany and Russia differ slightly in species composition and mycotoxin production capacity. CONCLUSIONS: We identified that the A. infectoria species group can be differentiated from the A. alternata, A. arborescens and A. tenuissima species group by colour, low mycotoxin production and by the sequence variation in TEF1-α gene. SIGNIFICANCE AND IMPACT OF THE STUDY: These results allow a reliable toxic risk assessment when detecting different Alternaria fungi on cereals.

[Inhibition of matrix metalloproteinases 9 and 13 affects the degree of lymphocytic infiltration and the expression levels of microRNA miR-21 and miR-let-7b in melanoma cells in vivo].

OBJECTIVE: To estimate changes in the trend of growth of primary tumor nodules, the degree of lymphocytic infiltration, and the expression levels of oncomicroRNA miR-21 and miR-let-7b when inhibiting matrix metalloproteinases 9 and 13 (MMP-9 and MMP-13) in vivo in C57B16 mice with transplantable melanoma B-16. MATERIAL AND METHODS: Tumor growth was evaluated measuring the volume of primary tumor nodules; the degree of lymphocytic infiltration was microscopically estimated using hematoxylin-eosin-stained tissue specimens, by calculating intratumoral lymphocytes. The expression of oncomicroRNA was quantified by real-time PCR. RESULTS: It was shown that MMP-9 and MMP-13 inhibition had no impact on the growth of primary tumor nodules; selective MMP-9 inhibition failed to affect the degree of lymphocytic infiltration of a primary tumor nodule and to change the expression of oncomicroRNA miR-21 and miR-let-7b; the concomitant inhibition of MMP-9 and MMP-13 altered the immunogenic properties of melanoma, stimulated the lymphocytic infiltration of tumor nodules, and decreased the expression of oncomicroRNA miR-21 and miR-let-7b; the degree of lymphocytic infiltration of primary tumor nodules increased in the dynamics of a tumor process and the expression levels of oncomicroRNA remained unchanged. CONCLUSION: The concomitant inhibition of MMP-9 and MMP-13 affects prognosis and survival in skin melanoma.

Russian study of morphological prognostic factors characterization in BRAF-mutant cutaneous melanoma.

Melanoma is one of the aggressive cancer types causing the majority of deaths in skin cancer patients. Mutational screening of the tumor revealed a number of driver mutations in oncogenes which enabled melanoma classification into a few molecular subtypes. BRAF is a key component of mitogen-activated kinase pathway; its activating mutation leads to accelerated melanoma cells proliferation, invasion and survival. Somatic mutations in BRAF were reported in various malignancies, including thyroid cancer, colorectal cancer and melanoma. Specific features of BRAF-positive tumors could have clinical implications as mutational alterations may have an impact on the biological behavior of the tumor and prognosis of the disease. In the present study, the frequency of BRAF V600E mutation was evaluated in Russian patients with melanocytic lesions, of which 41.25% were primary melanoma and 60% were melanocytic nevi. Melanoma patients with trunk localization were of younger age in the BRAF-positive group as compared with BRAF-negative patients. Immunohistochemical evaluations of Ki-67 expression, as well as matrix metalloproteinase-2, -9, were found to be equal in BRAF-positive and BRAF-negative tumors. MMP-2/MMP-9 immunoreactivity was observed in stromal and/or melanocytic cells both in melanoma and nevi patients. Besides tumor cells, MMP-9 expression was observed in lymphocytes in 27.2% of BRAF-positive and in 19.1% of BRAF-negative patients. Histopathological prognostic markers (Breslow thickness, mitotic index, ulceration, tumor infiltrating lymphocytes pattern) did not show any differences depending on BRAF V600E mutational status. The frequency of BRAF-positive melanomas in Russian cohort is similar to other Caucasian population rates. BRAF V600E mutation harboring tumors are more often observed in younger patients without specific features of morphological prognostic factors.

[Endometrial vasculature in women with hydrosalpinx].

OBJECTIVE: To study the endometrial vasculature in women with hydrosalpinx and to determine a possible correlation between its state and the morphometric parameters of other structural components of the uterine mucosa. SUBJECTS AND METHODS: The endometrium was studied in 20 patients with primary tubal infertility in hydrosalpinx. A control group included 20 women with established fertility and a regular menstrual cycle with a good obstetric and gynecological history. The spectrum of morphometric parameters included the relative volumes occupied by the endometrial glands and glandular epithelium; the height of the integumentary epithelium; and the number of stromal cells per mm2. Stereometric (glandular-stromal, epithelial-stromal) indices and epithelium/glandular lumen ratio were calculated. The endometrial vasculature was estimated by immunohistochemical assay of CD31- and CD34-expressing cells. RESULTS: There was a decrease in the specific volume occupied by positively stained vascular endotheliocytes and a predominance of the stromal component of the endometrium over its epithelial one. Correlations were found between the degree of development of the endometrial vasculature and endometrial glands, which reflects their normal relationships in the proliferation phase. In the study group, the correlation between the height of the integumentary epithelium and the development of the endometrial vasculature was moderately positive, which was absent in the control group where this correlation was strong and positive. The findings are evidence in favor of the negative impact of hydrosalpinx on the uterine mucosa. The found changes in the main endometrial structural components (vessels, glands, and stromal cells) reflect impaired mucosal maturation processes during the proliferation phase. The substantial negative impact of hydrosalpinx has an effect on the height of the integumentary epithelium of the endometrium. CONCLUSION: The given data suggest that there are significant and complex endometrial changes in hydrosalpinx. Suppressed angiogenesis is one of the key moments in the chain of impairments in the preparation of the uterine mucosa for implantation.