Vol 14, No 4 (2015)
REVIEWS
3-8 357
Abstract
CSCs are a tumor cell subpopulation that is a potential cause of cancer therapy resistance, recurrence and metastasis. This is the reason cscs seem a promising target for developing new approaches in anticancer treatment. Several mechanisms have been revealed that allow cancer cells to acquire CSC phenotype making malignant tumor treatment much more complicated. One of such mechanisms is a variant of epithelial-to-mesenchymal transition and e-cadherin loss, which results in cells with CSC characteristics occurring in carcinomas. The purpose of the present study is to review possible ways if cscs formation in human carcinomas.
DEVELOPMENT OF CANCER DIAGNOSTICS AND MONITORING METHODS BASED ON ANALYSIS OF TUMOR-DERIVED EXOSOMES
9-18 537
Abstract
Exosomes are small (80 - 130 nm) membrane vesicles secreted by virtually all cell types. The main physiological function of exosomes is considered to transfer substance and information from cell to cell. The biochemical composition of exosomes retains similarities with the cell of origin and reflects their endosomal biogenesis; moreover exosomes contain various signaling and regulatory molecules, components of the extracellular matrix and enzymes. Malignant transformation is associated with the activation of the exosomes secretion by cells. Cancer cell - derived exosomes are shown to play essential role in disease progression. The most significant effects of exosomes include suppression of anti-tumor immunity, stimulation of invasive growth and metastasis, the development of chemo- resistance. Tumor-derived exosomes can be detected in biological fluids, including blood. Exosomes are biochemically stable, their complex composition determines the possibility of comprehensive analysis. Thus, circulating exosomes have emerged as a promising source of cancer diagnostics material as it was demonstrated by number of studies. Although many substantial and methodological questions still remain to be addressed. This review briefly summarizes the current concepts of exosomes biology and discusses the main methodological aspects of exosomes research. Results of recent investigations aimed to develop new methods for cancer diagnosis and monitoring based on the analysis of exosomes and exosomal components are presented in great details.
ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ
N. A. Lyzhko,
A. V. Misyurin,
T. V. Ahlynina,
Y. P. Finashutina,
E. V. Aksenova,
I. N. Soldatova,
V. A. Misyurin,
A. Yu. Baryshnikov
19-30 301
Abstract
The problem on the localization of the protein PRAME in cancer cell remains unclear. We have created two antibodies, that specifically recognize PRAME epitopes. Using them, we have checked the localization of PRAME protein in some cell lines, including K562 and mel Kor, that characterized by high PRAME gene expression level, original lines B16F10 and WI-38, and B16F10 and WI-38, that transfected by PRAME gene. Finally, we have investigated the PRAME localization in acute myeloid leukemia patient's bone marrow cells. We have shown, the PRAME protein are localisated in nucleus, cytoplasm and plasma membrane of cells with high PRAME gene expression levels. PRAME protein localisation only in cytoplasm and plasma membrane in cells with lower gene expression level. Moreover, our antibodies demonstrated cytotoxic effect during co-incubation with PRAME1 cells.
31-38 447
Abstract
Multiplexed suspension systems of anew generation are capable to provide precise quantitative profiling of mul- tipledisease-specific markers in human body fluids. We have developed suspension microarrays based on microbeads encoded with fluorescent nanociystals, that show undeniable advantages overavailable analogues in terms of improved multiplexing capabilities, physical and optical properties, low cost and simplicity of analysisperformance. We have adapted QD-encoded suspension microarrays for the simultaneous detection of two forms of prostate-specific antigen (PSA) in human serum by means of classical flow cytometiy. In the present study, we describe in detail the designed system properties including evaluation the microarray for quantitative analysis of serum markers in comparison to standard clinical approach ELISA, as well asestimation of the most important analytical characteristics, such as analytic sensitivity (limit of detection), reproducibility, reliability and accuracy of the analysis, the linear rangesfor detectable- marker concentrations. Experimental data suggested that the developed diagnostic system quantifies two forms of PSA in blood serum samples of patients with high accuracy, precision and reliability.
D. A. Afanasieva,
M. A. Baryshnikova,
T. N. Zabotina,
A. A. Borunova,
O. S. Burova,
E. Yu. Rybalkina,
A. A. Nikolina,
Z. G. Kadagidze
39-44 406
Abstract
MDR is the main obstacle to chemotherapy efficiency. MDR can grow in cancer cells even if only the one cytostatic agent will act. The aim of the nowadays work is to characterize MDR in metastatic human skin melanoma cell lines prepared in “N.N. Blokhin Russian Cancer Research Center”. pgpl70 expression was detected by immunofluorescence methods. mRNA of MDR gene was identified by Reverse Transcriptase- PCR( RT-PCR) method. Rhodamine 123 (Rhl23) emission has been evaluated by flow cyto- fluorimetiy, cytotoxic activity was estimated by MTT-tests. The cells sensitivity to Aianoza cytostatic effects has showed that mel Kor cells were sensitive to Aranoza acting, but mel Ibr and mel Mtp X were not. Mel Ibr cells had expressed pgpl70 from 35 to 50 per cent, it was detected by immunofluorescence reaction. Mel Kor and mel Mtp-X cells were not expressed P-glycoprotein. mRNA of genes responsible for multi-drug resistance - MDR1, BCRP, MRP1 and LRP (MVP) - were detected by PCR. mRNA of BCRP and MRP1 genes has low expression, barely visible stripes after 33 cycles in all cell lines samples. LRP (MVP) genes expression of mRNA, unfortunately, never managed to see. YB1 gene mRNA expression is well, it is typically for cancer cells. mRNA of gene was found in mel MtpX and mel Ibr subclones cell lines. Mel Kor cells didn't contain mRNA of MDR1 gene. The study of the Rhl23 emission from cells showed that mel Kor control cells had accumulated Rhl23 and didn't throw it out. Mel Ibr cell line accumulated Rhl23 and threw out the half part of it. Mel MtpX cell tine had accumulated the less part of Rhl23 and almost all were thrown out. Thus, the study shows that mel Kor cell tine that are sensitive to Aranoza doesn't express pgpl70, not contain mRNA of multi-chug resistance genes and does not throw Rhl23. Mel Ibr cells resistant to the Aranoza cytotoxic action express pgpl70 ,contain mRNA of MDR1 gene and throw out Rhl23. However, mel MtpX cell line resistant to Aranoza does not express pgpl70, but contains mRNA of MDR1 gene and actively throws out Rhl23.
E. R. Pereverzeva,
I. D. Treschalin,
E. V. Voznyakovskaya,
M. I. Treschalin,
T. B. Pereverzeva,
N. V. Eremkin,
N. V. Bulushova,
E. P. Sannikova
53-58 374
Abstract
Toxicological study of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female inbred rats. L-asparaginase was injected intraperitoneally at the 1 and 10 therapeutic dose (15x1200 IU/kg or 15x12000 IU/kg with 24-h interval). Dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed 1 and 15 days post treatment. At necropsy, the organs were inspected macroscopically. The mass coefficients of heart, kidneys, liver, spleen and thymus were calculated. The pathomorphological evaluation was performed for internal organs. The results of the study demonstrate that the treatment with L-asparaginase Was79 did not produce any changes in body weight, hematology, blood biochemical or urinary parameters. Hematological, renal, gastrointestinal, and pancreatic toxicity of L-asparaginase have been documented only by microscopic pathology observation. Liver toxicity, revealed in the histopathological findings, was supported by the results of clinical chemistry. Marked elevation of ALT and alkaline phosphatase in serum was found in both treated groups. Most of these abnormalities were reversible and dose-dependent.
59-64 317
Abstract
The research has been devoted to the study of acute toxicity of preparation based on derivative of indolocarba- zole - LCS-1208 in mice of both sexes and in rats of both sexes at intravenous and intraperitoneal administration of the drug. In the experiments the laboratory animals - outbred white rats and hybrid mice (C57Bl/6JxDBA2)Fl (B6D2F1) have been used. On the results of study has been obtained the calculated toxic doses of novel preparation based on derivative of indolocarbazole at intraperitoneal administration of the drug in mice of both sexes.
65-72 373
Abstract
The paper presents the results of the study of «acute» toxicity and some results of the study of «subchronic» toxicity of Ormustin, a new anticancer drug belonging to nitrosourea class, in small laboratory animals. In the experiments the laboratory animals - hybrid mice (C57Bl/6J×DBA/2)F1 male and female and outbred male and female rats have been used. On the results of study has been obtained the calculated toxic doses of Ormustin at intravenous administration of the drug in mice and rats; has been given the preliminary assessment of the impact of Ormustin on organs and systems of rats at multiple intravenous administration.
E. V. Sanarova,
A. V. Lantsova,
Xi Zhang,
M. V. Dmitrieva,
A. P. Polozkova,
O. L. Orlova,
Z. S. Shprakh,
M. P. Kiseleva,
L. M. Borisova,
Z. S. Smirnova,
N. A. Oborotova
73-78 368
Abstract
At present, the hormone somatostatin analogues is increasing interest in connection with their activity against hormone-dependent tumors, which leads to the need to develop domestic drugs belonging to this group. In the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin RCRC» synthesized new domestic pentapeptide somatostatin analogue of hypothalamic hormone (AGGS). In preliminary studies of this substance demonstrated sufficiently high antitumor activity AGGS on transplanted solid tumors of mice. Due to the insolubility of the substance in the water as an alternative liposomal formulation proposed, allowing to increase the bioavailability of the drag due to the possibility of intravenous administration, increased therapeutic efficacy and reduce side effects, by improving the selectivity of action against tumor cells. During experiments on the development of the liposomal formulation AGGS pre-established model containing as essential components of the liposomal bilayer and egg lecithin PEG-2000-DSPE in a molar ratio 72/1 and as a ciyo- protectant - sucrose. In developing the technological parameters of the process of obtaining dosage form (LF) found that for an acceptable size derived phosphohpid vesicles needs about 7 cycles extrusion. The lack of stability of liposomal dispersion selected composition during storage has led to this problem by means of freeze-drying, which kept the physico-chemical parameters LF at the initial level. The efficacy of the model LF on transplantable tumors of mice - breast adenocarcinoma Ca-755, which was more than 60 % of ITG at a dose of 5 mg / kg and more than 80 % ITG with 20 mg / kg. The findings of biological experiments indicate the prospects for further research and improvement liposomal LF to produce high-performance domestic anticancer drag from the group of somatostatin analogues.
M. A. Kaplan,
A. I. Malygina,
G. V. Ponomarev,
A. A. Mikhailovskaya,
V. V. Drozhzhina,
L. M. Arkhipova,
J. S. Osipchuk
79-85 380
Abstract
Antitumoral therapy of sarcoma M-l of rats is spent with use of the combined method of treatment (photodynamic therapy and radial therapy) at various sequences of its carrying out, at different time intervals and parametres of a laser irradiation. A photosensitinogen dose amidoaminchlorine and a gamma radiation dose were identical at all spent researches. The purpose: to study influence of all components of combined therapy and to define optimum conditions of its carrying out for achievement of significant antitumoral effect in comparison with monotherapy of each of them. As a result of researches intensifying of inhibiting effect is taped at complex therapy and optimum parametres of its carrying out are found.
ТЕЗИСЫ. МАТЕРИАЛЫ XII ВСЕРОССИЙСКОЙ НАУЧНО-ПРАКТИЧЕСКОЙ КОНФЕРЕНЦИИ С МЕЖДУНАРОДНЫМ УЧАСТИЕМ «ОТЕЧЕСТВЕННЫЕ ПРОТИВООПУХОЛЕВЫЕ ПРЕПАРАТЫ»
S. S. Brusov,
A. V. Efremenko,
V. S. Lebedeva,
E. Yu. Shchepelina,
Ph. V. Ponomarev,
A. V. Feofanov,
A. F. Mironov,
M. A. Grin
87-92 430
Abstract
A neutral photosensitizer, aminobutylamide chlorin e6 with a terminal amino group (1), and its derivative, a cationic photosensitizer with a terminal trimethylammonium group (2) were synthesized. Spectral, photophysical and photobiological properties of compounds 1 and 2 were studied. An impact of a charge in molecule 2 on a photoinduced antitumor activity was evaluated in vitro. Relative coefficients of intracellular accumulation (Krei) were determined for compounds 1 and 2 in human lung adenocarcinoma A549 and human glioblastoma U251 cells. The coefficients of intracellular accumulation of neutral chlorin 1 in both cell types are fivefold higher than those of cationic chlorin 2. As a consequence, compound 1 surpasses fifteen-fold compound 2 in photoinduced cytotoxicity.
A. A. Pankratov,
T. N. Andreeva,
R. I. Yakubovskaya,
A. D. Kaprin,
A. A. Konarev,
T. V. Yakunina,
E. A. Lukyanets
93-98 445
Abstract
We developed the original preparation Lymphotest on the basis of disulphoderivative of diaminotriphenylmet- anic dye, differing from Lymphazurin by positions if sulphogroups in benzene ring - N-[4-[[4-(diethylamino)phenyl] (2,5-disulfophenyl)methylene]-2,5-cyclohexadien-l-ylidene]-N-ethylethanaminium hydroxide, inner salt, sodium salt. The proposed compound practically does not differ by spectrum from Lymphazurin, but is much more accessible and highly lymphotropic. Lymphotest in the form of 1% aqueous solution is characterized by a high diagnostic efficiency when using direct color lymphography, low toxicity (imposed dose exceeded the anticipated maximum dose for a human in 50-1000 times) and has no locally-irritating effect when using subcutaneously.
КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ
L. I. Korytova,
V. P. Sokurenko,
E. A. Maslyukova,
A. V. Meshechkin,
N. D. Oltarzhevskaya,
M. A. Korovina,
I. V. Gusev,
A. D. Kuznetsov,
V. G. Krasnikova,
E. M. Obuhov
99-103 406
Abstract
The article is devoted to the effectiveness evaluation of the use of sterile material «Kolegel 5-ftur» on the basis of sodium alginate with 5-fluorouracil, as of shape of disk, in the course of chemoradiotherapy in patients with rectal cancer, breast cancer and cancer of the floor of the mouth. The study group included 38 patients: 19 patients diagnosed with CRR, 10 patients -BC, 9 patients - a cancer of the mouth floor. The study used a hydrogel material «Kolegel 5-ftur» during chemoradia- tion therapy for histologically confirmed diagnosis of a malignant tumor. The effectiveness of the combined treatment is proved by the following criteria: local control of the tumor, the analysis of toxicity and immediate effect. Thus, the use of hydrogel materials «Kolegel-5-ftur» in group of patients with primary malignant tumor localization in the floor of the mouth, with the aggressive chemotherapy provided enhancing the effectiveness of therapy.
ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)
ISSN 1726-9792 (Online)