Introduction. the ability of the small intestine (internalization) to absorb water-soluble anticancer cytostatics determines the possibility of their oral administration. the ex-vivo express method that simulates the internalization of substances using a modified technique of an isolated «inverted» segment of the rat small intestine with flash chemiluminescence is adequate to solve the problem. Objectives: to evaluate the absorption of the new water-soluble anticancer cytostatics with different properties from the rat small intestine for preclinical study by oral administration. Material and methods. conjugated with acridinium (Acridinium NHS Ester, Toronto Research Chemicals, Canada) cytostatics were studied: low molecular weight (1) anthrafuran-acridinium (MW 0.8 kDa) and high molecular weight (2) aimpila-acridinium (MW 105 kDa) and (3) L-lysine-α-oxidase (LO-acridinium, MW 122 kDa). absorption was determined in a modified model of an isolated «inverted» segment of the rat small intestine using flash-chemiluminescence with the calculation of the relative light units (RLu). Results. It was shown that the absorption level of acridinium-conjugated cytostatics depending on molar concentration ranged from 55 % (1) to 1.7–11 % (2, 3) and 2500 (1) to 9.2–188 nmol/l (2, 3), respectively. the level of internalized anthrafuran-acridinium (55 %) was consistent with the known value of the effective non-conjugated cytostatic oral dose, which was two times higher than equitherapeutical parenteral dose: 100 mg/kg vs 50 mg/kg. Conclusion. the data obtained allow us to consider ex vivo express method for preclinical study of the various water-soluble anticancer cytostatics for screening and identification of an opportunity for oral administration and estimation of starting dose. the method has a good correlation with in vivo tests and economically favorable due to a quick response and small number of the tested agent.

The review presents a discussion on articles and patents, describing new in vitro and in vivo models of pigmented or non-pigmented human cutaneous melanoma, received in NMRCO from the patients» metastases. Molecular genetic characteristics of the new models is supported by the arguments in addition to the given data and visual materials. The subjects of the discussed publications are 3 polyclonal cell lines, 2 subclones and 4 subcutaneous (s/c) xenografts in immunodeficient mice Balb/c nude. All the models are stored in Cryo Collection with xenografts at N.N. Blokhin NMRCO as well as in the Russian Collection of Cell Cultures of Vertebrae (RCCCV, St. Petersburg). This mini-collection is recommended for use in basic research of cutaneous melanoma and pre-clinical studies of anti-melanoma agents. The basis for these studies are the appropriate characteristics of the models, including cytological, immunologic, transplantation and molecular-genetic ones, as well as in vivo drug sensitivity to the corresponding target therapy.

Введение.Разработка новых ортотопических моделей опухолевого роста (surgical orthotopic implantation, SOI) открывает возможность доклинического изучения потенциального антиметастатического действия препаратов, в том числе направленных на лечение диссеминированного светлоклеточного рака почки, с использованием в качестве имплантата фрагмента опухоли или метастаза от пациента.Использование подкожного (п/к) ксенографта открывает возможность оптимизации SOI с расширением возможностей применения в эксперименте.Наличие п/к ксенографта РПоч1, охарактеризованного трансплантационно, морфологически, иммунологически и по чувствительности к классическим противоопухолевым цитостатикам в коллекции опухолевых штаммов ФГБУ «Российский онкологический научный центр им.Н. Н. Блохина» Минздрава России, позволяет получить ортотопическую модель для полифункционального применения при доклиническом изучении новых специфических лекарств

Introduction. Development of new models of a human disseminated skin melanoma of the with molecular-genetic targets for specific therapy increases productivity of the preclinical researches new the anti-melanoma drugs or their combinations in vitro and in vivo. Such opportunity is realized by adaptation in vivo of the original human pigmented skin melanoma cell line mel Cher and receiving subcutaneous (s. c.) xenograft under monitoring of transplant, morphological, molecular-genetic (V600E BRAF mutation) and chemotherapeutic (sensitivity for the inhibitor of BRAF kinases to a vemurafenib) characteristics. Objective: receiving from the cell line mel Cher s. c. xenogratft of the human pigmented skin melanoma with V600E BRAF mutation and sensitive to specific target therapy. Materials and methods. Human pigmented skin melanoma cell line mel Cher from the Collection of Russian Cancer Research Center and immunodeficient Balb/c nude female mice cultivated in Russian Cancer Research Center was used. Required characteristics are defined by multiple s. c. transplanting in vivo by methods of transplant biology, a light microscopy, molecular-genetics and the experimental chemotherapy. Sensitivity to a BRAF kinase inhibitor to a vemurafenib was estimated under monitoring of the tumor growth rate (Vt/V0) on indexes, adequate for patients: existence of the complete remission and possibility of recurrence. Results. When s. c. transplantation of 107 cell of mel Cher line cytological identical intertwined s. c. xenografts with a stable growth kinetics on 4-9 passages (a latent phase 8 days, exponential - to 14 days, stationary - to 24 days) and existence of a mutation of V600E BRAF have been recieved. Vemurafenib in a single dose of 75 mg/kg caused the complete remission during a 15-day course and within 7 days after its cancellation - with the subsequent recurrence. Conclusion: receiving from the cell line mel Cher s. c. xenogratft of a human pigmented melanoma of skin with a mutation of V600E BRAF and sensitive to specific target therapy is suitable for preclinical studying of the new anti-melanoma drugs specific for this target.

Pharmaceuticals derived from plants, have become one of the leading commercial directions in modern biotechnology. The benefits that offer these technologies, cannot be matched with any other modern technology for producing drugs from recombinant proteins. Main advantages of plant technologies for production of proteins are easy scalability, efficiency, bio-safety, ease of cultivation and collection of biological material. This approach promises to be the most perspective for production of a wide range of drug substances and vaccines. In current investigation we have analyzed in vitro and in vivo biological activity of plant-derived anti-HER2 recombinant antibodies - phytotrastuzumab. Phytotrastuzumab and trastuzumab have similar activity in grows suppression of breast cancer cells overexpressing HER2 in-vitro and were active in suppression of xenografted tumors SK-BR-3 in-vivo.

Luminescent porous silicon nanoparticles with mean size of about 100 nm were covered by biodegradable polymer (dextran) and were investigated as potential sensitizers for ultrasound-assisted therapy. Luminescent confocal microscopy revealed an efficient uptake of the nanoparticles by cancer cells in vitro. The nanoparticles were found to be almost nontoxic up to the concentration of 0.1 mg/mL and doses of 30 mg/kg as it was confirmed by in vitro and in vivo experiments, respectively. A strong suppression of the cancer cell proliferation was observed after a combined treatment by the nanoparticles and therapeutic ultrasound irradiation with frequencies of 1-3 MHz and intensities of 1-2 W/cm(2). The obtained results are discussed in view of potential applications of biocompatible and biodegradable silicon-based nanoparticles in sonodynamic therapy of cancer. (c) 2015 Elsevier Inc. All rights reserved.

The experience of the joint research by the Department of Chemistry, Lomonosov Moscow State University, and the Federal State Budgetary Scientific Institution "N.N. Blokhin Russian Cancer Research Center" (FSBSI "N.N. Blokhin RCRC"), on the application of medium-intensity ultrasound in combination with chemotherapy and sonosensitizers in the treatment of cancer diseases was summarized. A cycle of preclinical trials showed that the method allows enhancing the damaging effect of ultrasound on the tumor, while no metastasis-promoting and toxic effects are exerted. The combined method is being currently tested in clinical trials.

Sonodynamic therapy in combination with antitumor drugs and sonosensitizers (theraphthal and its derivatives) was studied in preclinical testing against malignant tumors. The use of this therapy scheme enhances the destructive effect of ultrasound on tumors, promotes no metastasis, and make therapeutic drugs more bioavailable. The scheme was recommended for clinical use. A solid-phase sonosensitization mechanism was proposed. A possible system of laboratory and in vitro testing for selection of efficient sonosensitizers was outlined.