[Clinical and cytogenetic factors of prognosis in glial tumors of the brain].

BACKGROUND: The purpose of this study is to assess clinical, morphofunctional and molecular factors of prognosis in patients with malignant cerebral gliomas. MATERIALS AND METHODS: Retrospective analysis of follow-up of surgical and complex treatment of 95 patients with cerebral gliomas was performed. The series included 81 primary case and 14 recurrent cases. In all patients age, sex, clinical, topographic, morphological and therapeutic factors were analyzed. In 47 patients molecular and genetic prognostic factors including p51, MGMT, p16, PTEN and hyperproduction of miRNA21 in tumor cells were investigated. RESULTS AND CONCLUSIONS: We established significant prognostic factors for cerebral gliomas. They include: histological nature, age, sex, comorbidity. Complex treatment of glial tumors (surgical resection + radiation therapy) correlated with longer life expectancy in comparison with patients who received only surgical treatment. Patients wish mutations in tumor cells had longer survival period in comparison with mutation-free patients. This finding allows application of molecular and genetic tumor markers as independent prognostic factors in glial cerebral tumors.

[Characteristics of methyl-specific PCR-test of glutathione-S-transferase P1 gene in plasm DNA and cellular urinary precipitate for differential diagnosis of prostatic adenoma and adenocarcinoma].

The study was made of possibilities of methyl-specific PCR-test of glutathione-S-transferase P1 (GSTP1) gene in differential diagnosis of prostatic cancer: sensitivity of the test, comparison of reagents of Russian and foreign production. Blood plasm and cellur urinary precipitate DNA was investigated in patients with prostatic adenocarcinoma. The results show that the above test with domestic reagents is rather perspective for differential diagnosis.

[The methodological specificity of PCR-test of gene p53 in plasma and blood cell DNA of oncological patients]. / Metodicheskie osobennosti PTsR-analiza gena p53 v DNK plazmy i kletok krovi onkologicheskikh bol'nykh.

The evaluation of mutations in the p53 gene is of a big value for the laboratory diagnostics in oncology. The p53 gene was analyzed, within the present case study, in blood plasma, in which tumor-origin DNAs were detected, as well as in blood cells and in tumor tissue. Optimal conditions were defined for polymerase chain reaction (PCR) with primers. The adequacy of the conditions selected for PCR and for SSCP-electrophoresis, when used in the analysis of mutations in exons 5-8, gene p53, was shown by the method of direct sequencing. The first results on revealing the frequency of gene-p53 mutations were obtained for some of the oncology diseases in the studied population.

[Molecular genetic aspects of the antineoplastic effect of gluthoxim]. / Molekuliarno-geneticheskie aspekty protivoopukholevoi aktivnosti preparata glutoksim.

Gluthoxim--bis(g-L-gluthamyl)-L-cystenyl-bis-glycin disodium salt (C20H32O16N6S2)--is an analog of oxidized gluthation with a stable disulfide bond. It is a drug of a new class of thiopoetins which regulate thiol disulfide metabolism. Gluthoxim is used as a support substance in chemotherapy of cancer. The present investigation deals with feasibility of gluthoxim-induced apoptosis in tumor cell cultures, including human myeloleukema cells HL60 which lack protein p53 gene, so crucial for apoptosis. Also, gluthoxim effect was studied with respect to transformed murine fibroblasts C8 and A4, carrying the plasmide structure with Ras and E1A genes which boost Ras-gene expression. This in turn makes fibroblasts ready to start apoptosis. Gluthoxim induction of cell death was demonstrated in both cell lines; however, apoptosis in cells C8 (with intact gene p53) was much more pronounced than in cells A4 without this gene. It is suggested that apoptosis can be triggered by both imbalance of redox potential typical of tumor cells, induction of p53 synthesis and an impact on the phosphoproteinase cascade of Ras-signal pathway.

[The potentials of molecular genetic diagnosis in military medicine (a review of the literature)]. / Vozmozhnosti molekuliarno-geneticheskoi diagnostiki v voennoi meditsine (obzor literatury).

The practical importance of the main genetic infringements in diagnostics of a wide circle of illnesses, including cardiology, nephrology, and oncology. Methods used. The exclusive effectiveness of application of the polymerasic chain reaction in the purposes of diagnostic. Expediency of application of the molecular-genetic methods for radiating, chemical and extreme effects evaluation.

[Methods for DNA diagnosis in military medicine]. / Metody DNK-diagnostiki v voennoi meditsine.

The article makes a review of achievements in the sphere of biotechnology and genetic engineering as far as military medicine is concerned. A special attention is drawn on diagnostic capacities of molecular genetic methods which analyse DNA and RNA objects. Principles of modern diagnostical methods are described which are based on molecular hybridization of nucleic acids with a use of specific DNA probes or polymerize chain reaction (PCR). The advantages of the latter are shown in the comparison with immunochemical methods. Peculiarities of new quantitative PCR modifications are studied. The article contains data concerning the use of DNA probes and PCR for estimation of radiation injuries and during formation of maximal tolerance level of physical and chemical influence.

[DNA analysis of retroposon-like genetic LINE elements in blood plasma of rats exposed to radio-diapason electromagnetic waves]. / Analiz DNK retrotranspozonpodobnykh geneticheskikh élementov LINE v plazme krovi krys, podvergshikhsia vozdeistviiu élektromagnitnykh voli radiodiapazona.

The elevation of LINE-elements' DNA level was revealed in blood plasma of rats exposed to electromagnetic waves. The amount of full-size 5'-containing LINE-elements copies was increased especially. Connection of this effect with retrotransposon activation and genetic instability condition of organism development is supposed.

[Polymerase chain reaction and ligase reactions. Principles, traditional methods, and innovations]. / Polimeraznaia tsepnaia reaktsiia i ligaznye reaktsii, printsipy, traditsionnye metodiki i novovvedeniia.

The polymerase chain reaction (PCR) is a favorite among the diagnostic DNA probes. Besides the traditional PCR scheme, the author considers the new strictly quantitative modifications representing a combination of PCR with semiautomated immunoassay, this simplifying the practical use of the method. Errors most frequently occurring in PCR are discussed. The ligase chain reaction, more rapid than PCR, and permitting one to obtain a billion of DNA molecule copies in 30 min, is described, and prospects of its use for rapid diagnosis shown.

[Changes in the content and fractional composition of blood plasma nucleic acids in radiation lesions. The effect of radioprotectors]. / Izmenenie soderzhaniia i fraktsionnogo sostava nukleinovykh kislot plazmy krovi pri radiatsionnykh porazheniiakh. Effekt radioprotektorov.

The content of DNA in blood plasma increased in early stages after irradiation (2 and 5 h), the low-molecular DNA (160-180 bp) being revealed as opposed to intact animals. Protection of gamma-irradiated rats by cystamine or gammaphos enhanced this phenomenon. The injections of cystamine and gammaphos to nonirradiated animals stimulated DNA ejection into blood stream in 2 h only with normalization by 5 h. Cystamine was the most effective, and in experiment with non-irradiated animals the low-molecular DNA was detected for cystamine only.

[Structure of low-molecular DNA in the blood plasma of irradiated rats]. / O strukture nizkomolekuliarnoi DNK plazmy krovi obluchënnykh krys.

Low-molecular DNA in blood plasma of rats appeared after gamma-irradiation in a dose 8-100 Gy. This DNA has been cloned and the 26 clones have been sequenced. The search for sequence similarity between the designated sequences and sequences in EMBL allowed the three homology to LINE 3 sequences to be found. The differences in the structure of low-molecular DNAs extracted from rat blood plasma after irradiation of rats in doses 8 and 100 Gy were not found.

Extracellular DNA level in the blood of irradiated rats.

There is high-molecular DNA in the blood of unirradiated rats which moves as a single fraction during electrophoresis in 0.5% agarose. At short times (2-5 h) after gamma-irradiation at doses from 1 to 100 Gy a low-molecular species of DNA appears (about 180 nucleotide pairs), the amount of which is directly proportional to exposure dose at 5 h after exposure. It has been established by Southern hybridization that the low-molecular DNA has few nucleotide sequences common with those of the high-molecular DNA, but it shows homologously to genomic sequences.

[Contents of extracellular DNA in blood of irradiated rats]. / Soderzhanie vnekletochnoi DNK v krovi obluchennykh krys.

Intact rat plasma contains high-molecular DNA which moves as a single fraction in 0.5% agarose electrophoresis. As early as 2-5 hours after gamma-irradiation in a dose of 1-100 Gy there appears low-molecular DNA (about 180 nucleotide pairs), the amount of which directly correlates with the irradiation dose 5 hours after the exposure. Blot-hybridization showed that low-molecular DNA has no common nucleotide sequences with high-molecular DNA, though has sites similar to genome repeat sequences.

[Detection of the determinants of tetracycline A, B and C resistance in Shigella and Salmonella using DNA probes]. / Opredelenie determinant resistentnosti k tetratsiklinu klassov A, B i C u shigell i sal'monell s pomoshch'iu DNK-zondov.

Genetic determinants of tetracycline resistance of classes A, B and C were detected with DNA probes labeled with radioactive phosphorus (32P) in Shigella (44 strains) and Salmonella (50 strains). It was shown that in the Shigella strains the frequency of the Tet A gene amounted to 66 per cent, the frequency of the Tet B gene was equal to 84 per cent, the frequency of their combination was equal to 50 per cent and the frequency of the Tet C gene was nil. In the Salmonella strains the frequency of the Tet A, Tet B and Tet C genes was equal to 0.100 and 20 per cent, respectively, and that of their combination amounted to 20%. Possible use of the DNA probes in epidemiological analysis of outbreaks of Shigella and Salmonella infections is suggested.

[Changes in the serum fraction composition of nucleic acids in radiation injuries. Alterations in an early period after gamma-irradiation of rats]. / Izmeneniia fraktsionnogo sostava nukleinovykh kislot syvorotki krovi pri radiatsionnykh porazheniiakh. Narusheniia v rannie sroki posle gamma-oblucheniia krys.

The content and fractional composition of nucleic acids of blood serum change after lethal (8 Gy) particularly superlethal (100 Gy) gamma-irradiation of rats. This concerns DNA the content of which increases by 7 times 5 h following 100 Gy irradiation. It has been shown by electrophoresis in 0.85% agarose that a heterogeneous DNA fraction with the molecular weight of (1-15) X 10(6) dalton increases. The analysis of the preparation in the polyacrylamide gel has revealed a DNA fraction that is not found in norm: the fraction possesses the electrophoretic mobility corresponding to that of nucleosome DNA.

[3H-thymidine incorporation into the DNA of the nucleic factor in the ascitic fluid of Ehrlich cancer]. / Vkliuchenie 3H-timidina v DNK nukleinovogoo faktora astsitnoi zhidkosti raka Erlikha.

After intraperitoneal administration of 1.85 MBq 3H-thymidine to mice with Ehrlich ascites tumours the maximal radioactivity of nucleic factor DNA of ascitic fluid was observed when the isotope had been injected 5-6 days before extraction of ascitic fluid (4-5.10(5) cpm/mg). The maximal radioactivity of DNA of tumour cells themselves was registered when 3H-thymidine was administered 2 days prior to tumour ascites extraction (5.2.10(5) cpm/mg). The administration of even 37 MBq 3H-thymidine 1.5 h before the ascitic fluid extraction from the Ehrlich ascites tumours did not result in the incorporation of this radioactive precursor into nucleic factor DNA. The results obtained show that there is an interval (several days) between the nucleic factor DNA synthesis and its secretion.