[Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines].

INTRODUCTION: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form. OBJECTIVE: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses. MATERIALS AND METHODS: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay. RESULTS: 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 109 to 1 × 1010 copies/ml. CONCLUSION: Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

Human Diploid Fibroblast Cell Lines - a Model System for Studying Immunodulatory Properties of Modern Immunobiological Drugs and Viruses.

The immunomodulatory properties of immunobiological drugs Glutoxim and Phosprenyl we well as vesicular stomatitis virus and inactivated tick-borne encephalitis vaccine virus were studied using human diploid fibroblast cell line from the collection of M. P. Chumakov Federal Research Center for Research and Development of Immunobiological Products. All tested preparations exhibited immunomodulatory activity in human diploid fibroblast cell line. Glutoxim in doses of 0.1 and 0.25 µg/ml stimulated production of IL-6 and IL-10 during 24-48 h of culturing, but did not stimulate production of IL-1ß. Phosprenyl, on the contrary, increased production of IL-1ß and the levels of IL-6 and IL-10. Vesicular stomatitis virus stimulated the production of IL-1ß, IL-6, and IL-10, while inactivated tick-borne encephalitis vaccine virus stimulated the production of cytokines IL-8 and IL-18. Immunomodulatory activity of inactivated tick-borne encephalitis vaccine virus was first demonstrated in the in vitro system.

Selection of Domestic Cell Lines for the Creation of Diagnostic and Preventive Preparations against Enterovirus 71.

We studied the sensitivity of domestic proprietary human and animal cell lines from the collection of M. P. Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products to infection with different enterovirus 71 strains. A cell system based on domestic proprietary permanent cell line 4647 was for the first time used for reproduction of four enterovirus 71 strains (BrCr, 42266, 42934, and 43374). It was shown that strain 4647 is the optimal cell substrate for enterovirus 71 reproduction. The titers of enterovirus 71 for all four strains considerably (by 2 lgTCID50/ml and more) increased during sequential passages in permanent cell line 4647. The prospects of using permanent cell line 4647 for creation of diagnostic and preventive preparations against 71 was demonstrated.

[THE USE OF COMBINATION ANTIVIRAL THERAPY IN LIVER CIRRHOSIS HCV ETIOLOGY].

Is a clinical example of combination antiviral therapy drugs interferon and ribavirin in the treatment of liver cirrhosis in chronic HCV infection, class A on Child-Pugh which made the transition of liver cirrhosis in the F1 fibrosis (the Metavir) and achieved sustained antiviral response (SVR).

[Antifibrotic properties of lidase in experimental berylliosis]. / K voprosu o protivofibroznykh svoistvakh lipazy pri eksperimental'nom berillioze.

The effect of lidase with its inhalation against the background of a fibrotic process in the lungs was studied on a model of experimental berylliosis provoked in rats through intratracheal administration of 5 mg of Be (OH)2. The degree of fibrosis was assessed according to the dry residue in the lungs, content therein of oxyproline, hexosamines and hexuronic acids. Lidase was found not only to delay the development of the affections but also to lower the level of fibrosis existing prior to the treatment. The therapeutic effect of the compound continued for a comparatively long time.

[Distribution and activity of pyridoxal kinase in human brain during ontogenesis]. / Raspredelenie i aktivnost' piridoksal 'Kinazy v mozge cheloveka v protsesse ontogeneza

The activity of pyridoxal kinase was sharply increased in whole brain tissue of human, embryos and fetuses within 6-11 weeks of development. In brain stem the maximal values of the enzyme activity was observed at early stages of prenatal development of fetuses. The activity of pyridoxal kinase was increased in cerebral cortex and in the limbic system up to complete maturation of fetuses. It correlated with the fetus age within 14-40 weeks of development as calculated per 1 g of tissue wight or 1 mg of protein. The enzyme is distributed evenly in brain of newborns, babies and adult people. Its activity in grey cortex substance is higher, than in white one. There are 2-10-fold individual fluctuations of pyridoxal kinase activity in brain of people without CNS pathology. In newborns, having prolonged hypoxy at prenatal period, the enzyme activity was on the average by 70-80% lower at different brain parts than in newborns which had no primary asphyxia. A low pyridoxal kinase activity (not more than 1-5% as compared with its normal level) was observed in different brain parts of a child affected by focal gliosis and epilepsy.