Репозиторий Университета

© 2019, Pleiades Publishing, Inc. Abstract: Angiomyolipoma (AML) is one of the most frequent and, at the same time, AML molecular genetics is one of the least studied among benign tumors. We performed deep sequencing of 409 genes involved in oncogenesis in tumor samples and peripheral blood of patients with sporadic AML of the kidney. We recorded mutations in the TSC2 gene in 65% of samples, which is consistent with international results. As a result of our work, we uncovered mutations in the SETD2, PDGFRA, STK36, SYNE1, PIK3CD, NF1, TOP1, and ITGB3 genes in sporadic renal AML for the first time. In two samples, we were able to clarify the clinical and morphological diagnosis by finding mutations in the genes in tumors lacking TSC2 gene lesions. Mutations in MET and CDC73 are also causative for other types of renal tumors: papillary renal cell carcinoma and CDC73-related disorders, respectively. The latter disease is accompanied by kidney cysts and hamartomas. The obtained results demonstrate a promising potential of mutational profiling of sporadic renal angiomyolipoma (sAML). Genotyping of sAML is particularly important for clarification of the clinical diagnosis in ambiguous cases, as well as for a more in-depth understanding of AML molecular genetics and etiopathogenesis, and for the identification of new molecular targets for personalized AML therapies.

© Bionika Media Ltd. Different factors caused by both equipment and the course of surgery (conditions under which the operation is performed, the location of incision, the characteristics of suture material, the type of surgical suture, and the amount of blood loss), by the course of the postoperative period, and the peculiarities of repair of damaged tissues influence wound healing of the uterus during cesarean section. Objective. To establish the value of premature amniorrhea and uterine inertia as predictors of impaired myometrial repair after cesarean section, by using clinical and morphological analyses. Subjects and methods. The investigation enrolled 129 patients who had given birth via cesarean section. Of them, 44 patients had delivery before birth activity, 85 during the first stage of labor. 49 and 80 women delivered before and after amniorrhea, respectively. During cesarean section, uterine tissue was taken from the upper edge of the wound after uterine incision. The myometrial biopsy specimens obtained during cesarean section were morphologically and immunohistochemically examined. The patients were divided into 4 groups according to the level of birth activity and the preservation of amniotic fluid at the time of cesarean section. Group 1 included patients with regular labor activity and amniorrhea at the time of caesarean section; Group 2 consisted of those with labor activity in the presence of whole amniotic fluid; Group 3 comprised those without birth activity in the presence of whole amniotic fluid; Group 4 included patients with premature amniorrhea without uterine contractions. 36 cases (9 in each group) were selected by random sampling for morphological and immunohistochemical examinations. The biopsy specimens were fixed in 10% neutral formalin and embedded in paraffin. The serial paraffin-embedded sections underwent histological examination and immunohistochemical tests for the following markers: TGF-β, VEGF, MMP2, TIMP1, types I and III collagen, TNF, and PDGF. Results. The morphological and immunohistochemical analyses revealed the most pronounced signs of myometrial damage during cesarean section in Group 4 patients having premature amniorrhea without uterine contractions. There were decreased VEGF, PDGF, MMP2, and TIMP levels and simultaneously increased TNF-α expression in leiomyocytes, vascular endothelium, and myometrial stromal cells. The findings may indicate the relatively lower reparative potential of the myometrium and the increased readiness for an inflammatory response in the group of women undergoing cesarean section in the presence of premature amniorrhea without uterine contractions. Conclusion. Clinical, morphological, and immunohistochemical analyses have revealed differences in the myometrial status in relation to typical clinical factors, such as amniorrhea and birth activity. Wound healing occurs under the influence of growth factors and the ratio of expression levels for growth factors can vary in different pathological conditions. The reduced expression of VEGF, MMP2, TIMP, and PDGF and the increased expression of TNF in the group having amniorrhea without uterine contractions (P-B+) suggest that there are pronounced inflammatory processes and impaired myometrial repair with the longer latency period in the absence of labor activity, which may refer these women to a group at risk for incompetent scar formation.