Рисунок 1. Два механизма, используемые микро-РНК для регуляции трансляции. Некоторые miRNA способны полностью комплементарно связываться с таргетными мРНК, что вызывает их деградацию. Микро-РНК также могут быть не полностью комплементарны мишеням, тем самым, трансляция блокируется. Адаптировано из [147].
e13506 Background: Gliomas are the most common type of primary brain tumors, with a high level of recurrence and mortality. The purpose of the study was to determine the expression profile of micro-RNA targeting components of the Hedgehog, Notch, Wnt, EGFR, TGFβ, HIF1α signaling pathways according to MirTarBase, miRDB, TargetScan. Methods: The study included 30 patients (15 women and 15 men) aged 27 to 76 years with histologically verified glial brain tumors. The RT2-qPCR method in operational biopsy specimens determined the relative expression of 12 micro-RNAs: hsa-miR-17-3p, hsa-miR-20a-3p, hsa-miR-326, hsa-miR-330-3p, hsa-miR- 107, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-146a-5p, hsa-miR-29a-3p, hsa-miR-92a-1-5p, hsa-miR-26b-3p, hsa-miR-96-5p. Hsa-miR-7-5p and hsa-miR-126-3p were used as reference micro-RNA. Results: A statistically significant increase in the expression of hsa-miR-143-3p, hsa-miR-146a-5p and hsa-miR-92a-1-5p by 2, 2.2 and 2.9 times, respectively, was found, as well as a decrease in the expression of hsa-miR-330- 3p by 4.1 times in tumor tissue of the brain relative to normal tissue (p < 0.05). Reduced expression of micro-RNA hsa-miR-330-3p may increase the activity of the VEGFA gene, which leads to intensive vascularization of the tumor. In addition, hsa-miR-330-3p is a validated negative regulator of the E2F1 gene known as a regulator of the cell cycle and tumor suppressor proteins. The TRAF6 gene is the direct validated target of hsa-miR-146a-5p, and its overexpression is associated with the patient's chemoresistance to temozolomide. Increased hsa-miR-143-3p micro-RNA expression can reduce the activity of the EGLN1 gene that also mediates the adaptation of tumor cells to hypoxic conditions. Hsa-miR-92a-1-5p micro-RNA is a negative regulator of PTEN gene expression. Conclusions: A significant decrease in hsa-miR-330-3p expression and an increase in hsa-miR-146a-5p, hsa-miR-143-3p, and hsa-miR-92a-1-5p, which was found in gliomas, can potentially be used to develop prognostic markers and therapeutic targets for targeted therapy.
e13510 Background: The high rates of mortality from venous thromboembolism (VTE) in neurooncological patients determine the relevance of the topic. The risk of VTE in patients with glioma reaches 36% during the treatment period, 16.1% during the first 6 months and increases by 3 times after tumor biopsy. The aim of this study was to evaluate the efficacy and safety of VTE treatment with fondaparinux after surgical interventions for brain tumors. Methods: The study included 32 cancer patients aged from 27 to 76 years (mean 56.5 years) in the acute period of VTE, the first month after craniotomy. Creatinine clearance below 30 ml/min, active bleeding, thrombocytopenia below 50x109/l were exclusion criteria. Glioma was diagnosed in 15 patients (46.9%), metastasis - 9 (28.1%), and meningioma - 8 patients (25%). Radical interventions were performed in 12 (37.5%) cases, palliative - 20 (62.5%). In 81.2% of cases (26 patients) deep vein thrombosis of lower extremities (DVT) was detected, 3 patients (9.4%) had combination with pulmonary embolism. VTE developed in the postoperative period with radiotherapy in 9 cases (32%), dexamethasone - 13 (40.6%). Surgical treatment of DVT was performed in 8 patients (thrombectomy, plication of the femoral vein). Segmental deep vein thrombosis of the lower leg was detected in 14 (43.8%) cases. Results: The efficiency of anticoagulant therapy was assessed by a decrease of thrombinemia markers (fibrinogen, SFMC and D-dimer). After a week of anticoagulant therapy, a significant reduction in the level of D-dimer was observed. However, the decline in fibrinogen and SFMC was statistically insignificant. VTE therapy was performed with fondaparinux in a therapeutic dose from 10 days to 1 month, followed by a transition to oral anticoagulants. There was no hospital mortality. Hematuria developed in one case (3.1%), and was managed conservatively. There were no hemorrhagic complications in the operative intervention zone. Two patients (6.25%) had a recurrence of VTE during the period of radiation therapy. Conclusions: An integrated approach to the treatment of VTE in patients undergoing craniotomy provides a low incidence of recurrent VTE and major bleeding.
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