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Adzerikho I.E.,Belarusian Medical Academy of Post Graduate Education | Mrochek A.G.,Republican Scientific and Practical Center Cardiology | Minchenya V.T.,Scientific and Technological Park of the BNTU | Dmitriev V.V.,Belarusian Research Center for Pediatric Oncology and Hematology | Kulak A.I.,National Academy of Sciences of Belarus
Ultrasound in Medicine and Biology | Year: 2011

To prevent a distal embolization in the course of ultrasound (US) angioplasty, we combined US thrombus disruption in peripheral artery in vivo with simultaneous administration of streptokinase (SK). Acute thrombosis was induced in the femoral arteries of 23 dogs. Two hours after thrombus formation, thrombus destruction was performed using US (36 kHz) and by a combined US+SK (75,000 U/kg) administration. The results showed that thrombi were disrupted completely by 1.5 ± 0.5 min US. A combined US+SK action resulted in activation of fibrinolysis, as indicated by the increase in the content of fibrinogen and fibrin degradation products and D-dimers by a factor of 1.5-2.0 after 120 min from start of treatment compared with the SK lysis. The duration of clot destruction did not change; the distal embolization was not indicated; platelet aggregation activity dropped after thrombus destruction. In summary, intravascular thrombus destruction by a combined US and SK action in vivo is accompanied by enhancing the enzymatic fibrinolysis and lowering the platelet aggregation activity that assists in preventing the distal embolization of the resulting clot debris. © 2011 World Federation for Ultrasound in Medicine & Biology. Source

Savitskaya T.V.,Belarusian Research Center for Pediatric Oncology and Hematology
Pediatric hematology and oncology | Year: 2012

For better understanding cancer pathogenesis and searching a potential target for antineoplastic therapy, the authors have studied mRNA expression profile in tissues from 39 children with histological confirmed malignant sarcomas and from 23 patients with bone and soft tissue nonmalignant lesions. mRNA levels of Angiogenesis-related genes VEGFA (including isoforms of 121, 165, 189), VEGFC, VEGFR-1, VEGFR-2, VEGFR-3, HIF-1α, TF, TFPI-1, TFPI-2, uPA, PAI-1 in pediatric specimens were examined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). uPA, HIF-1α, VEGFR-1, VEGFR-2, VEGFR-3, and VEGFC mRNA levels from nonmalignant tissue were significantly higher than those from cancer tissue. On the other hand, isoform VEGFA121 and VEGFA165 and ratio VEGFA165/189 mRNA levels in cancer were higher in comparison with nonmalignant tissue. There was a strong correlation between VEGFA165 and VEGFA189 mRNA expression levels both in cancer tissue and in nonmalignant tissue. In grade 4 tumors in comparison with grade 2 tumors, there was a reduced VEGFA165/189 ratio. Moreover, TFPI-1 and TFPI-2 mRNA levels were significantly lower in sarcomas than in nonmalignant lesions and TFPI-2 was significantly lower in grade 4 tumors than in grade 2. The present data suggested that mRNA overexpression of angiogenesis-related genes is not a prerogative of malignant tissues. The authors supposed that in pediatric bone and soft tissue pathology, high expression of mRNAs of some angiogenesis-related genes may be associated with inflammation and physiological angiogenesis rather than with the development of a malignant tumor. The authors showed the importance of VEGFA121 and/or VEGFA165 and VEGFA165/189 isoform ratio in pediatric sarcomas neoangiogenesis and TFPI-2 for tumors grade 4. Source

Meleshko A.N.,Belarusian Research Center for Pediatric Oncology and Hematology | Vashkevich K.P.,Belarusian Research Center for Pediatric Oncology and Hematology | Fomina E.G.,Republican Research and Practical Center for Epidemiology and Microbiology | Scheslenok E.P.,Republican Research and Practical Center for Epidemiology and Microbiology | And 2 more authors.
Experimental Oncology | Year: 2013

Aim: Idiotype, the unique part of immunoglobulin molecule expressed on the surface of B-cells, represents a specific antigen for vaccination against lymphoma. We have developed a rapid method for immunoglobulin variable fragments cloning, assembling and expression of recombinant idiotype protein in Escherichia coli. Methods: PCR with specially designed panel of primers was used for direct amplification of variable regions of tumor immunoglobulin. Overlapping extension PCR, restriction and ligation was applied for assembling and cloning of vaccine construction. Idiotype protein was purified by metal-chelate chromatography. Results: Methods of idiotype cloning from lymphoma cells and production of recombinant protein were developed and optimized. Several samples of idiotypic proteins originating from B-cell lines and lymphoma patients were produced. Conclusion: The proposed method of vaccine production is relatively cheap, not very laborious and requires as long as 6-7 week to perform. The expressed protein was soluble, did not accumulate in inclusion bodies and harvested at sufficient for vaccination quantity and concentration. Source

Fridman M.V.,Republic Center for Thyroid Tumors | Fridman M.V.,Belarusian Research Center for Pediatric Oncology and Hematology | Savva N.N.,Belarusian Research Center for Pediatric Oncology and Hematology | Krasko O.V.,Belarusian Research Center for Pediatric Oncology and Hematology | And 5 more authors.
Thyroid | Year: 2012

Background: A systematic analysis of the clinical and pathologic patterns of childhood "sporadic" thyroid carcinoma in Belarus, in the absence of the "Chernobyl radioactive iodine factor," has never been performed. The aim of this study was to establish the essential features of "sporadic" papillary thyroid carcinoma (PTC) in Belarusian children and adolescents, and the relationship of tumor pathology to extrathyroidal extension (ETE) and lymph node metastases. Methods: This was a retrospective population-based study with assessment of histological samples of 119 cases of thyroid cancer in Belarusian children and adolescents of 0-18 years old registered during 2005-2008 years. Sporadic PTC was noted in 94 children who were not exposed to the Chernobyl radiation release. None of the 119 cases of thyroid were follicular thyroid cancer. Results: The incidence rate of PTC was 1.13 per 100,000 persons. The median age at diagnosis was 15.1 years with fourfold predominance of diagnosis in female patients. Relapse was detected in 2% of cases with median follow-up of 4.2 years. Median tumor size was 12 mm. Three percent of the cases of PTC had multifocal growth. The classical variant of PTC was registered in 46% of the patients with thyroid cancer, the follicular variant of PTC was noted in 20% of the cases. The percent of rare types of PTC (tall cell and diffuse sclerosing) were equal to that for solid PTCs (13%, 12%, and 10%, respectively). Adolescents had a pure papillary carcinoma more often compared to children who represented tumors with mixed papillary/follicular patterns more frequently (p<0.05). Two-thirds of the patients with PTC had regional lymph node metastases. ETE was established in 39 of 74 patients in whom ETE could be assessed by morphology. Multivariate analysis showed that lymphatic invasion was the strongest independent factor associated with both ETE (p<0.0001) and lymph node metastases (p<0.0001). Conclusion: In 2005-2008, sporadic thyroid cancer in children of Belarus was represented by high prevalence of PTC and absence of follicular thyroid cancer. Sporadic cases of PTC in Belarus were characterized by smaller tumor size, a small number of cases with multifocal growth, an equal number of rare types and solid PTCs, a relatively high prevalence of pure papillary variant of PTC in adolescents, and a low frequency of early relapses. A high frequency of ETE and lymph node metastases was detected. The strongest morphologic factor associated with both of them was lymphatic invasion. © 2012, Mary Ann Liebert, Inc. Source

Meleshko A.N.,Belarusian Research Center for Pediatric Oncology and Hematology | Savva N.N.,Belarusian Research Center for Pediatric Oncology and Hematology | Fedasenka U.U.,Belarusian Research Center for Pediatric Oncology and Hematology | Romancova A.S.,Belarusian Research Center for Pediatric Oncology and Hematology | And 4 more authors.
Leukemia Research | Year: 2011

Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT). MRD positivity, as well as quantitative level of MRD were analyzed and compared between patients who stayed in remission and relapsed. Relapse-free survival revealed to be significantly associated with MRD levels at different time points. Unfavorable prognosis was shown for MRD≥10 -3 on day 36 (p<0.001), and any positive MRD before (p<0.001) and after (p=0.001) MT. Multivariate Cox regression analysis proved MRD as independent significant prognosis factor at day 36 (p=0.005) and before MT (p=0.001). We conclude, that MRD quantified by RQ-PCR in children with ALL treated with ALL-MB protocols is feasible and independently associated with outcome. MRD may be a suitable parameter for treatment stratification in MB protocols in future. © 2011. Source

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