Иммунотерапия онколитическими вирусами (ОВ) становится полноценным методом неоадъювантной терапии в парадигме доказательной медицины для все большего числа онкологических заболеваний. Особенно актуально применение ОВ для иммунологически «холодных» опухолей, вызывающих минимальный иммунный ответ и обладающих выраженным иммуносупрессивным опухолевым микроокружением. Для стимуляции противоопухолевого ответа применимы рекомбинантные ОВ, несущие последовательности иммуноактивирующих белков. Целью работы было исследовать онкоселективность и противоопухолевую активность рекомбинантного ОВ, созданного на базе штамма LIVP вируса осповакцины, экспрессирующего последовательности интерферона-альфа человека и мыши (hIFNα и mIFNα соответственно). В экспериментах с помощью метода Рида и Менча было показано, что созданные рекомбинантные ОВ проявляют онкоселективность в отношении опухолевых линий соответствующего вида. Для LIVP-hIFNα показана способность эффективно заражать линии аденокарциномы и глиобластомы человека. Для LIVP-mIFNα in vitro продемонстрирована селективность в отношении глиомы Gl261 и меланомы B16. В эксперименте in vivo на мышах линии C57Bl/6 c подкожной меланомой В16 показана способность LIVP-mIFNα после внутривенного введения уменьшать объем подкожного аллографта опухоли и увеличивать инфильтрацию опухоли CD8+- и NK-клетками. Созданный рекомбинантный вирус может быть потенциальной платформой для разработки онколитической виротерапии меланомы и глиобластомы человека.

Sredi onkoliticheskih virusov odnim iz naibolee izuchennyh yavlyaetsya virus ospovakciny (VV), shtamma modificirovannogo vysokoattenuirovannogo virusa Ankara (MVA), pokazavshego mnogoobeshchayushchie rezul'taty v doklinicheskih i klinicheskih ispytaniyah. SHtamm Lister VV iz Moskovskogo Instituta virusnyh preparatov (LIVP) issledovan v men'shej stepeni, chem MVA i imeet otlichnyj ot MVA tropizm. Cel'yu raboty bylo sravnit' onkoliticheskuyu effektivnost' shtammov LIVP i MVA v otnoshenii solidnyh opuholej. Dlya povysheniya selektivnosti LIVP i MVA k opuholevym kletkam nami byli polucheny rekombinantnye varianty s inaktivaciej gena timidinkinazy (TK), MVA-RFP i LIVP-RFP, ekspressiruyushchie krasnyj fluorescentnyj belok. Kinetiku replikacii i onkoliticheskuyu aktivnost' poluchennyh rekombinantnyh shtammov ocenivali in vitro i in vivo na liniyah opuholevyh kletok i allotransplantatah myshinyh singennyh modelej metastaticheskoj adenokarcinomy molochnoj zhelezy myshi 4T1, adenokarcinomy tolstoj kishki CT26 i melanomy B16. Kak MVA-RFP, tak i LIVP-RFP pokazali vysokuyu effektivnost' replikacii v opuholevyh kletkah i vyrazhennuyu onkoliticheskuyu aktivnost' v otnoshenii allotransplantatov melanomy V16 i adenokarcinomy molochnoj zhelezy 4T1. V otnoshenii 4T1, yavlyayushchejsya model'yu trojnogo negativnogo raka molochnoj zhelezy cheloveka, LIVP-RFP po sravneniyu s MVA-RFP pokazal bolee chem na 50% povyshennuyu citotoksichnost' v testah in vitro, a takzhe dostovernoe zamedlenie progressirovaniya allotransplantatov 4T1 i povyshenie vyzhivaemosti zhivotnyh v eksperimentah in vivo. Primenenie shtamma LIVP v kachestve platformy pri razrabotke rekombinantnyh onkoliticheskih virusov dlya terapii raka molochnoj zhelezy mozhet byt' bolee perspektivnym, chem primenenie shtamma MVA.

Electroconvulsive therapy (ECT) is the effective way of treatment for drug-resistant depression. However it was demonstrated that in some cases ECT may exert a temporary negative effect on memory, which confine its application in practice. In our study we tried to estimate the effect of ECT on cognitive function of Sprague-Dawley rats under normal conditions and under modeling of depressive-like disorder. After two series of behavioral experiments the absence of ECT negative effect on rats cognitive functions was demonstrated.

Fluorescent diagnosis was first proposed in the early XX century and has been used in neurosurgery for about 15 years. The method relies on selective accumulation of strongly fluorescent protoporphyrin IX in tumor cells. Over the past years, the method of intraoperative fluorescence diagnosis has occupied its niche in many neurosurgical clinics around the world and is now used for fast intraoperative diagnosis in brain tumor surgery. However, the efficiency of fluorescent intraoperative diagnosis using 5-aminolevulinic acid is 80-90% and 58.8% for surgery of Grade III-IV and I-II gliomas, respectively. One of the methods to improve the efficiency of fluorescent diagnosis is to use vector systems for delivering fluorescent drugs into the tumor. This paper reports the results of an experimental study of systems for delivering fluorescent agents (protoporphyrin IX, Alexa 488, Alexa 660) using connexin-43 antibodies in rats with transplanted C6 glioma.

The results of fundamental and applied studies of blood-brain barrier had been conducted by authors during the last 10 years are summarized in the publication. The molecular anatomy of barrier microvessels, as well as promising markers of BBB and other proteins involved in barrier functions are discussed. Via in vitro experiments with endothelial cells of cerebral microvessels we characterized the basic conditions required for adequate BBB modeling. The in vivo data of BBB permeability for macromolecules in normal and different pathological processis including radiation injury, hyperosmotic shock, and nervous tissue ischemia are properly described. A particular attention was focused upon the experimental studies of the permeability and functional reorganization of barrier endothelium during tumor neoangiogenesis. We detected a dramatically increased permeability of neoplastic microvessels both for horseradish peroxidase/serum albumin and labeled monoclonal antibodies. The increased tumor permeability for IgG and the overexpression of target antigens in tumor tissue and peritumoral zone make possible the targeted delivery of diagnostics and therapeutic agents into the tumor by means of monoclonal antibodies.

This review is focused on up-to-date methods of radioimmune therapy and other approaches to the targeted treatment of high-grade gliomas. Radioimmune therapy with monoclonal antibodies to nucleoproteins, matrix and endothelial proteins and receptors of growth factors is discussed. New methods and themost promising techniques for the targeted treatment of gliomas (inactivation of signaling pathways, boron neutron capture therapy, targeted transport of nanoparticles by biomimetic protein vectors) are analysed.