Novosibirsk State Medical University
Novosibirsk, Russia
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Rusanov A.L.,Novosibirsk State Medical University | Luzgina N.G.,Novosibirsk State Medical University | Barreto G.E.,Pontifical Xavierian University | Barreto G.E.,Autonomous University of Chile | And 2 more authors.
CNS and Neurological Disorders - Drug Targets | Year: 2016

In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. © 2016 Bentham Science Publishers.

Nepomnyashchikh T.S.,Novosibirsk State Medical University | Antonets D.V.,Novosibirsk State Medical University | Maksyutov R.A.,Novosibirsk State Medical University
Medical Immunology (Russia) | Year: 2017

Over last decade, a substantial progress has been made, with respect to understanding of cancer biology and its interplay with the host immune system. Different immunotherapeutic drugs based on recombinant cytokines and monoclonal antibodies are widely used in cancer therapy, and a large number of experimental cancer treatments have been developed, many of which are currently undergoing various stages of clinical trials. Recent endorsement of a recombinant oncolytic herpesvirus T-VEC for the treatment of melanoma was an important step towards a more safe and efficient anticancer therapeutics. In this review, we shall mention only some of the most promising cancer immunotherapy strategies, namely, immune checkpoint inhibitors, cellular therapy and oncolytic viruses. © 2017, SPb RAACI.

Soboleva M.K.,Novosibirsk State Medical University
Pediatriya - Zhurnal im G.N. Speranskogo | Year: 2016

The article presents the current understanding of Anderson-Fabry disease (AFD)-historical aspects of this rare hereditary disease study, genetic decoding of various AFD variants, clinical picture of the disease in different stages, modern diagnosis and treatment possibilities, differential diagnosis issues. The article is focused on nephropathy accompanying AFD. © 2016, Pediatria Ltd. All rights reserved.

Porshennikov I.A.,Novosibirsk State Medical University
Sovremennye Tehnologii v Medicine | Year: 2017

The aim of the investigation was to analyze the techniques and results of right liver resections with vascular resections and reconstructions in advanced hepatic alveolar echinococcosis. Material and Methods. The retrospective study included 12 patients with advanced alveolar echinococcosis of the right part of the liver and parasitic invasion of portal vein bifurcation, and/or inferior vena cava, and/or hepatic veins confluence. The mean age was 47.6±18.3 years (from 21 to 65 years, median 57). Extended right hemihepatectomy (Sg4–8) was performed in 10 (83.3%) cases, right hemihepatectomy (Sg5–8) in 2 (16.7%) cases. Sg1 was removed in 11 cases, additional nonanatomic resection of Sg2 and Sg3 was performed in 1 case. Normothermic resection was used in 10 patients, in vivo in situ hypothermic perfusion in 1 patient, and ex vivo resection in 1 patient. Arterial resection was necessary in 2 cases, portal vein resection in 9 cases, inferior vena cava resection in 8 cases. inferior vena cava was reconstructed with a ePTFE-graft (1 case), autogenous vein graft (2), anastomosis (2), or by caval plasty (3). Results. Hospital mortality was absent. Surgical complications (Grade IIIb–IVa, Clavien–Dindo) were observed in 5 cases, bile leakage (Grade C, ISGLS) in 2 cases. There were no vascular complications and post-hepatectomy liver failure. The patients stayed in the intensive care unit for 9.0±8.5 days (from 3 to 34 days, median 6) and total length of hospital stay was for 34.0±16.1 days on average (from 13 to 70 days, median 33). During 19-month median follow-up there was no recurrence of the disease. Conclusion. Liver resection is the preferred treatment option and is feasible in the majority of patients with advanced alveolar echinococcosis in the absence of unresectable distant metastases, liver cirrhosis, Budd–Chiari syndrome and in the presence of technical possibility to preserve or reconstruct afferent and efferent blood circulation in the remnant liver. © 2017, Nizhny Novgorod State Medical Academy. All rights reserved.

Suhovskih A.V.,Novosibirsk State University | Aidagulova S.V.,Novosibirsk State Medical University | Kashuba V.I.,NASU Institute of Molecular Biology and Genetics | Kashuba V.I.,Karolinska Institutet | Grigorieva E.V.,Novosibirsk State University
Cell and Tissue Research | Year: 2015

Glycosylation changes occur widely in colon tumours, suggesting glycosylated molecules as potential biomarkers for colon cancer diagnostics. In this study, proteoglycans (PGs) expression levels and their transcriptional patterns are investigated in human colon tumours in vivo and carcinoma cells in vitro. According to RT-PCR analysis, normal and cancer colon tissues expressed a specific set of PGs (syndecan-1, perlecan, decorin, biglycan, versican, NG2/CSPG4, serglycin, lumican, CD44), while the expression of glypican-1, brevican and aggrecan was almost undetectable. Overall transcriptional activity of the PGs in normal and cancer tissues was similar, although expression patterns were different. Expression of decorin and perlecan was down-regulated 2-fold in colon tumours, while biglycan and versican expression was significantly up-regulated (6-fold and 3-fold, respectively). Expression of collagen1A1 was also increased 6-fold in colon tumours. However, conventional HCT-116 colon carcinoma and AG2 colon cancer-initiating cells did not express biglycan and decorin and were versican-positive and -negative, respectively, demonstrating an extracellular origin of the PGs in cancer tissue. Selective expression of heparan sulfate (HS) proteoglycans syndecan-1 and perlecan in the AG2 colon cancer-initiating cell line suggests these PGs as potential biomarkers for cancer stem cells. Overall transcriptional activity of the HS biosynthetic system was similar in normal and cancer tissues, although significant up-regulation of extracellular sulfatases SULF1/2 argues for a possible distortion of HS sulfation patterns in colon tumours. Taken together, the obtained results suggest versican, biglycan, collagen1A1 and SULF1/2 expression as potential microenvironmental biomarkers and/or targets for colon cancer diagnostics and treatment. © 2015, Springer-Verlag Berlin Heidelberg.

Krivoshapkin A.L.,Novosibirsk State Medical University | Zelman V.L.,University of Southern California
World Neurosurgery | Year: 2012

There is archaeological evidence that the first neurosurgical procedure in what is now known as Siberia was performed in 8005 ± 100 B.C. According to signs of bone growth, perhaps more than half of the individuals who received the ancient trepanations survived. In Siberia, the first operations on the human brain and spinal cord were performed in 1909 at Tomsk University Hospital by the outstanding Russian surgeon and professor Vladimir M. Mysh. Professor Mysh initially moved from Saint Petersburg to Tomsk and later to Novosibirsk. Nicolay N. Burdenko, the founder of Russian neurosurgery and the Moscow Neurosurgical Institution, began his medical education at the Tomsk Imperial University. In the 1950s, Professor Ksenia I. Kharitonova exerted her great influence upon the development of neurosurgery in Siberia. Since 1955, and for 30 years thereafter, Professor Kharitonova was recognized as a principal leader of Siberian neurosurgery. She applied every effort to spread neurosurgical knowledge, and she popularized best practices around Siberia and the Far East. Perestroika deconstructed and ultimately eliminated the orderly system of neurosurgical service in the Soviet Union. From another perspective, the process opened the window to the world. Fully equipped centers and clinics with state-of-the-art techniques for neuro-oncology, cerebrovascular diseases, neurotrauma, and spinal pathology management in Novosibirsk, Barnaul, Kemerovo, and Irkutsk were enabled. © 2012 Elsevier Inc.

Pupyshev A.B.,Novosibirsk State Medical University
Tsitologiya | Year: 2011

Lysosomal membrane labilizing agents (incl. proapoptotic proteins of Bcl-2 family, LAPF, p53), estimation of lysosomal membrane permeabilization in living cells, the new data on differential permeabilization of lysosomal membranes, membrane stabilizing factors (incl. Hsp70), relations between lysosomal membrane damage, and initiation of apoptosis were considered. Signal effect of lysosomal membrane permeabilization is caused preferentially by release of cathepsin B and D in cytosol. Subsequent numerous pathways of apoptogenic signalization include proteolytic attack/activation on signal cytosolic proteins, mitochondria, procaspases, cell nuclei. The mainstream of the cell damage is connected with activation pf proapoptotic Bid and Bax, leading to permeabilization of the outer mitochondrial membrane, release of cytochrome c into cytosol and activation of caspase cascade. Translocation of the lysosoma enzymes in cytosol is capable to induce both the caspase-dependent and caspase-independent paths of apoptosis.

Olennikov D.N.,Russian Academy of Sciences | Kruglova M.Yu.,Novosibirsk State Medical University
Chemistry of Natural Compounds | Year: 2013

A total of 48 compounds and the new flavonoid glycoside ulmarioside, which was identified as quercetin-4′-O-α-rhamnopyranosyl-(1→6)- β-glucopyranoside (quercetin-4′-O-rutinoside), were isolated from Filipendula ulmaria (Rosaceae). Phenolic compounds from six species of Filipendula (F. camtschatica, F. denudata,F. palmata, F. stepposa, F. ulmaria, F. vulgaris) growing in Russia were compared. © 2013 Springer Science+Business Media New York.

Kozlov V.A.,Novosibirsk State Medical University
Voprosy Onkologii | Year: 2016

There are numerous data in experimental and clinical medicine that convincing evidence on the leading role of the immune system in the pathogenesis of tumor diseases. Exactly immune cells such as cytotoxic T lymphocytes, NK cells, macrophages and dendritic cells have the ability to kill tumor cells. Under normal conditions the activity of these cells is a factor of inhibition proliferation and differentiation of tumor cells. An appearance of tumor itself, as uncontrolled cell growth and clinical manifestation, says that it was changed the cytotoxic activity of the cells causing tumor immunity. The main factor, if not the only reason for the decline of anti-tumor activity of the cells, is the formation of powerful extra- and inside-tumor suppressor mechanisms suppressing cytotoxic activity of anti-tumor immune-competent cells and allowing tumor cells to avoid surveillance by the immune system. It is showed that T and B cells, macrophages, and cells of myeloid origin suppressors possess these immunosuppressive properties. Therefore, in the future, methods to suppress functional activity of cells suppressors of various geneses can be the basis for immunotherapy of tumor growth.

Pupyshev A.B.,Novosibirsk State Medical University
Tsitologiya | Year: 2014

Molecular regulation of reparative/homeostatic autophagy induced by failure of vital resources and by cellular stress is considered. Extensive autophagy regulatory apparatus responds to starvation, insufficiency of growth factors and energy supply, accumulation of unfolded proteins (ER stress), reactive oxygen species, microbial invasion. Central sensor of the regulation is kinase mTOR. Part of the mTOR pool presented in lysosomes responds to the local level of amino acids and is able to induce autophagy under low rates of intralysosomal proteolysis. Autophagy is a self-regulated cell process, the peak of autophagy is followed by its regulatory weakening by amino acids formed in autophagolysosomes. Protective effect of autophagy is associated mainly with removal of permeabilized mitochondria generating ROS, and elimination of abnormally folded proteins. Autophagy has optimum of its activity: its deficiency leads to accelerated cellular aging, and the excessive autophagy brings to the deficiency of cellular survival resources and cell death. Autophagy cell death seems like a hyper- stimulated self-eating of the cell, but more probably that excessive autophagy disturbs cellular energy supply and switches on some specific cell death signalization (possibly associated with kinases c-Jun, DRP-1, PI3K class I etc.). Some approaches to use reparative autophagy for prevention of cell degeneration are considered.

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