Vol 16, No 2 (2017)
REVIEWS
6-12 396
Abstract
Prostate cancer (PC) incidence and mortality are growing steadily the world over including Russia. PC incidence in 2014 made up 14.3 % of all male tumors in the Russian Federation. PC mortality growth rate since 2004 turned out to be topmost among all men’s cancers. PC etiology is poorly understood yet. Thus the role of human papillomaviruses (HPV) belonging to the highly oncogenic types is unclear while in some other human organs they were proven to be powerful carcinogens. Communications keep on emerging from various laboratories by authors who make mutually exclusive conclusions on the role of these viruses in PC genesis. It seems urgent to clarify the given problem from both theoretical and practical viewpoints. Firstly, this is the way to specify the origin of such a common cancer type as PC is. Secondly, if PC association with oncogenic HPV is confirmed the outlook for PC prevention is discovered by means of inoculating of boys with the vaccines designed for cervical cancer prevention. The present review of the literature contains analysis of data on possible HPV involvement in PC genesis.
ORIGINAL REPORTS
E. R. Nemtsova,
O. A. Bezborodova,
N. B. Morozova,
M. S. Vorontsova,
J. B. Venediktova,
T. N. Andreeva,
E. I. Nesterova,
T. M. Andronova,
R. I. Yakubovskaya
13-22 457
Abstract
Objective of the study. To evaluate the pharmacological effects of N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-glutamic acid (GMDP-A) as a modifier of biological reactions, i. e. to study its modifying action in regard to traditional cytostatic chemotherapy. Materials and methods. The used drug agents were GMDP-A, cisplatinum, gemcitabine, cyclophosphamide, 5-fluorouracil. The transplanted murine tumors were Р-388 lymphocytic leukemia and S-37 sarcoma (solid and ascites variants), B-16 melanoma, CC-5 squamous cell carcinoma of the cervix uteri, C-26 adenocarcinoma of the colon, and AKATOL carcinoma of the colon (solid tumor variants). Efficacy indices were inhibition of tumor growth, and increase of life span of animals. Results. In the models of transplanted tumors in conventional mice, the influence of GMDP-A has been studied on therapeutic efficacy of cisplatinum (Р-388, S-37, В16, CC-5), 5-fluorouracyl (C-26, AKATOL), gemcitabine and cyclophosphamide (P-388) by using variations in single and total doses, time of the start of the treatment, as well as the route and site of the injection. It has been shown that GMDP-A has modified the efficacy of some cytostatic agents (cisplatinum, gemcitabine and cyclophosphamide) enhancing their antitumor activity irrespective of the location of the site of injection in regard to the tumor node. Conclusion. The obtained results proved the potency of GMDP-A as a modifier of biological reactions.
L. M. Borisova,
M. P. Kiseleva,
V. N. Osipov,
L. P. Sushinina,
S. V. Ustinkina,
L. I. Smirnova,
Z. S. Shprakh
23-29 381
Abstract
Introduction. Search of active compounds among cyphetrylin analogues is one of prospective directions in synthesis of new compounds that have higher resistance to fermentation. The report I presented the synthesis of new cyphetrylin compounds with various functional substituents (thiazolidin, naphthyl, rimantadine, chlorophenacyl and cyphelin), their presence on the surface of tumor cells when binding to receptors would enhance the cytotoxic effect of modified cyphetrylin compounds on tumor. Objective. The study of anti-tumor activity of the synthesized analogues cyphetrylin modified by cytotoxic agents. Materials and methods. The research was carried out on the transplanted murine tumors: breast adenocarcinoma Ca-755 and melanoma B-16. Drug solutions were prepared ex tempore with the use of dimethylsulfoxide or ethanol diluted with saline to a concentration of 10 % and was administered to female mice-hybrids F1 (C57Bl/6 х DBA/2) daily subcutaneous injection in doses of 5, 10, 20 and/or 30 mg/kg for 5 days. The criteria of antitumor effect served the tumor growth inhibition (TGI, %) and the increase in lifespan (ILS, %) of test animals compared to the controlled. Results. Boc-Cys(Thp) - Phe-D-Trp-Lys(ClPhe) - Thr-OMe - pentapeptide modified by chlorophenacyl lysine at Nc-group in a dose of 5 mg/kg on breast adenocarcinoma Ca-755showed a short-term antitumor effect directly after the end of the treatment (TGI = 73 %). Boc-Phe-D-Trp-Lys (Ac-Sar-Val) - Thr-OMe - tetrapeptide modified by cyphelin lysine at №-group in a dose of 10 mg/kg caused melanoma B-16 growth inhibition for 75-85 % within 4 days after the end of the treatment and increased lifespan (ILS) of mice for 29 %. Conclusion. 2 of 7 cyphetrylin analogues, modified by cytotoxic agents, showed antitumor activity, that indicate the prospects for their further research as antitumor compounds on other tumor models.
M. Yu. Reutovich,
Yu. P. Istomin,
O. V. Krasko,
H. M. Treshalina,
A. I. Shmak,
P. M. Bychkovsky,
T. L. Yurkshtovich,
N. V. Golub,
S. O. Solomevich,
Y. I. Rogov
30-35 496
Abstract
Introduction. Earlier it has been shown that the hydrogel (HG) on the basis of the dextran phosphate (DP) increases effectivity of cisplatin (CDDP) and especially prospidin (Pr) which at intraperitoneal (i.p.) therapy of the rat Zajdel ascite hepatoma (ZAH) the long-lived the complete remission (CR) of an ascites. It was assumpte that addition of the CDDP to HG/Pr with receiving double composition (HG/ Pr/CDDP) can lead to increase its efficacy. The purpose of research - the assessment of a possibility to increasing of efficacy i.p. therapy of an ZAH by the HG with Pr and CDDP. Materials and methods. It was used 55 white outbreed rats with ZAH (n = 7-10) by which obtained i.p. single therapy with HG/Pr/ CDDP in doses for Pr of 250 or 500 mg/kg and for CDDP of 3.0 of 5.5 mg/kg. Groups of comparison received HG/Pr in adequate doses. For assessment of effectivity the most significant index - number of the CR on accumulation of an ascites (control time - 42 days) with assessment of decrease in the relative risk (Cox model of proportional risks) and cumulative survival was chosen. Results. It is shown that efficacy of HG/Pr/CDDP when Pr was used in maximal doses of500 mg/kg was equal to HG/Pr, CR = 100 % against this model. When it was used Pr with subtherapeutic dose of 250 mg/kg CR = 0, but addition of the HG/CDDP led to CR = 50-70 % with depended on dose, and simultaneously with increase in cumulative survival up to pl mk = 0,004. The good tolerance of all therapeutic systems was evaluated. Conclusion. In rats with ZAH, a double composition of HG/Pr/CDDP in a high therapeutic dose for Pr of500 mg/kg is equally effective with HG/Pr in dose of 500 mg/kg, which makes it impossible to evaluate the therapeutic gain of adding CDDP. At a subtherapeutic dose for Pr of 250 mg/kg, a double composition with CDDP provides CR in a part of the rats. The obtained data confirm the importance of HG/Pr for intraperitoneal therapy of tumoral lesions of the human abdominal cavity, for which HG/CDDP acts as an adjuvant.
E. M. Uchanova,
T. M. Kulinich,
E. A. Kudiniva,
V. K. Bozenko,
S. M. Sitdikova,
M. S. Kalishjan,
H. M. Treshalina
36-41 399
Abstract
Introduction. Within constructed of molecules with a pathogenetic orientation to a tumor cell a row the chimeric of the peptides including the functional fragment with the amino-acid sequence from the SEQ ID NO group is created: 1 - SEQ ID NO: 17 and transport sequence. These peptides are capable at target delivery in the cells to find short functional domains in proteins regulators of various functions. Among them there is MM-D37K blocking G1 phase and inducing an apoptosis in the human tumor cells, including a colorectal cancer HCT-116. It is considered as the potential antineoplastic agent with the corresponding stages of studying. Aim. The aim of the study was an investigation of the MM-D37K dose characteristics at the parenteral administration on the human subcutaneous (s. c.) colorectal cancer xenografts HCT-116. Research problems. 1. Studying of the efficacy of MM-D37K in the dose range at multiple parenteral administration to the Balb/c nude mice with HCT-116. 2. Tolerance control of MM-D37K at multiple parenteral administration to the Balb/c nude mice with HCT-116. Materials and methods. Researches of a chimeric peptide MM-D37K (an inhibitor the cyclin-dependent protein kinases 4/6) are conducted on hypodermic s. c. colorectal cancer xenografts HCT-116 at immunodeficient Balb/c nude mice when using reference criteria assessment of efficacy and tolerance under adequate statistical processing of the results with use of nonparametric Mann-Whitney U-test. Results. It is shown that MM-D37K in single doses of 5 or 10 mg/kg at s. c. or intravenous (i. v.) 5-fold administration in 48 h (total doses 25 or 50 mg/kg) significantly and authentically inhibits the tumor growth within 9 days after the treatment on the level of T/C = 27-43 % (p <0.05) (reference criterion of T/C <42 %) at a well tolerance. At both routes of administration was observed the dose dependence foe efficacy as on T/C and on the maximal effect achievement. There was revealed big deviation of the tumor after the individual sensitivity to a peptide (variability of the tumor size at a larger dose by the i. v administration). Conclusion. The obtained data confirm the sufficient therapeutic range of a MM-D37K chimeric peptide in vivo on the model of a human colorectal cancer HCT-116 allowing to obtained significant reliable anticancer effect at parenteral multiple administrations in the double range of therapeutically doses.
N. P. Ermakova,
S. S. Trofimov,
N. Y. Kulbachevskaya,
O. I. Konyaeva,
V. M. Bukhman,
L. M. Michailova
42-49 583
Abstract
Introduction. Neurotoxicity is one of the specific systemic complications of anticancer chemotherapy. Detection in experimental animals complications of psychotropic or neurotropic action of the new drug is one of the most difficult challenges of preclinical toxicology. Preclinical toxicological study of the effect of a binary catalyst system «tereftal + ascorbic acid» on the central nervous system (CNS). Objective. The prediction of toxic effects of binary catalytic system in clinical application in patients. Materials and methods. The study was conducted on 300 male mice hybrids (CBA х C57 Bl/6J) F1. Have terephtal - russian drug. A binary catalyst system was injected intravenously once at close to the maximum tolerated dose - 50 mg/kg tereftal + 110 mg/kg ascorbic acid and in therapeutic dose - 20 mg/kg tereftal + 44 mg/kg ascorbic acid. The obtained data were compared with a control animal treated with saline solution and with the data of animals treated with one tereftal and one ascorbic acid in equivalent doses. To assess neurotoxicity tests used standard neuropharmacological screening. An assessment of emotional status, muscle tone were undertaken. Behavior was evaluated in the tests «open field» and «aggression». We evaluated the response to pain stimulation, the change in rectal body temperature. Higher integrative brain functions were investigated on the model of the conditioned reflex of passive avoidance. Estimated effect on convulsive readiness of the CNS. Results. The catalytic system changed the general condition of the animals. This was manifested, on the one hand, in the suppression of their overall activity (sluggishness, inactivity until weakness, muscle relaxation, the lowering side, the slowing of breathing), the other - to increase their excitability (when in group, some animals adopted a characteristic aggressive stands, in some cases seizures). These animals were observed exophthalmos, the appearance of the position «frog», posture «praying mouse», the desire to hide. The inhibitory effect of the catalytic system was dose-dependent. Observed inhibition of various forms of behavior, emotional status, decrease in body temperature and pain sensitivity, in the test for aggression - reducing the number of fights, in open field test - locomotor activity suppression. Spontaneous seizures in the provocation corazol binary catalytic system was not strengthened. Conclusion. The obtained data allow to predict toxic effects from the CNS during clinical use of binary catalytic system «tereftal + ascorbic acid»: total confusion, lethargy, physical inactivity, decrease in body temperature, increased anxiety and aggression and, in very rare cases, the occurrence of seizures.
O. I. Konyaeva,
N. Yu. Kulbachevskaya,
V. A. Chaley,
N. P. Ermakova,
A. A. Nikolina,
T. I. Malova,
V. M. Bukhman
50-59 451
Abstract
Introduction. The study investigates the embryotoxicity, teratogenicity and reproductive toxicity of lyophilized dosage form borchlorin on rats. Materials and methods. The research was conducted on 210 outbred female rats and 105 outbred male rats weighing 250-300 g. We used a lyophilized dosage form borated chlorin e6 called «Borchlorin liposomal, lyophilisates for dispersion for injection 2.5 mg». The drug was administered intravenously daily for 48 days (males) and 15 days (females) in 2 corresponding total doses for therapeutic dose in mice and rats based on the 10-therapeutic doses. As a control, intact rats were used, as well as rats - males and females who received intravenous 0.9 % sodium chloride solution into the mode corresponding to the mode of administration, and in the amounts corresponding to the maximum volume of the injected solution. Results of the study. To study the damaging effect of lyophilized liposomal formulation borchlorin on the generative function in rats - the identification of the possible negative effect of the drug on the progenesis stage (formation of male and female gametes). It was found that lyophilized liposomal formulation borchlorin has a damaging effect on the reproductive function of male and female and fetal deve lopment (embryotoxicity) rats on the index's ability to fertilization and conception and the index of postimplantation fetal loss. Postimplant death of the fetuses in most pronounced in females treated with a total dose of the drug, therapeutic doses corresponding to 10, coupled with intact males. The lyophilized liposomal formulation borchlorin pre-implantation does not cause the death of the fetus, has no teratogenic effects. Conclusion. The lyophilized dosage form borchlorin has a damaging effect on the reproductive function of male and female and fetal development (embryotoxicity) neinbrednyh rats on the index's ability to fertilization and conception and the index of postimplantation fetal loss. The lyophilized dosage form borchlorin pre-implantation does not cause the death of the fetus, has no teratogenic effects, effects on the physical development of the offspring, and the rate of maturation of the sensory-motor reflexes during the feeding of offspring.
N. V. Andronova,
L. F. Morozova,
N. M. Suraeva,
A. A. Lushnikova,
D. V. Filonenko,
S. M. Sitdikova,
I. N. Mihailova,
H. M. Treshalina
60-65 382
Abstract
Introduction. Drug sensitivity of metastatic .skin melanoma (SM) is rather low and bound, including, with various ability to a melanogenesis. Most often (70 %) dependent on RAF/MEK/ERK of an signal pathway therapeutic significant BRAF of a mutation are found in the amelanotic SM. In the N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia œllection of human melanoma cell lines is a culture of amelanotic SM mel Ibr/BRAF+ and its various subclones, including, subclone mel Ibr EE/BRAF+ suitable for creation of the models in vivo that are necessary for the final stage of preclinical studying perspective antimelanomа agents. Adaptation to the in vivo growth of these cell cultures is directed to receiving such model. Objective. Adaptation of the cell cultures of these SM to the growth at immunodeficient Balb/c nude mice by the subcutaneous implantation. There were a few positions: BRAF-V600E mutation verification in the cells; definition of number of cell doublings for calculation of an implanted dose for in vivo; implantation ability of SM cells into the Balb/c nude mice by s. c. inoculation; investigation of growth dynamics of measured s. c. tumor nodules in Balb/c nude mice. Materials and methods. For adaptation are used stable transplanted human SM cell of mel Ibr/BRAF+ and the its subclone of mel Ibr EE/BRAF+ which passed more than 30 passages in the same environment with the reduced content up to 5 % of fetal serum veal. V600E mutation in an exon of the 15 gene of BRAF was defined in SM cells, emitting genomic DNA from 3-day cell culture by means of the «AmplyPrime® DNA-sorb-V» set according to the instruction of the producer (NexBio Ltd., Russia). For searching of somatic mutations in an exon of the 15 gene of BRAF used polymerase chain reaction with the corresponding primers. Calculation of a implanted cell dose of each of SM cells is defined according to number of doubling cells, determined at cultivation by the relation of number of the dispelled cells which grew to quantity at a passage. The transplantable ability of the cells was controlled by hands and vision observation, the characteristics of the growth of subcutaneous tumor nodules with calculating of its dynamics was controlled by a morphometry. Results. It was shown, that proliferation level of mel Ibr/BRAF+ was a twice less than at its subclone mel Ibr EE/BRAF+: in 72 h the number of doubling makes 3 against 6. At implantation of the mel Ibr/BRAF+ in the maximal for in vivo inoculated dose of 1 x 107 cells on mouse the complete transplantable ability was not reached, the tumor left at 1 of 2 mice. At implantation of a subclone of mel Ibr EE/BRAF+ in a vaccinating dose 3 x 106 cells on a mouse the inoculation took place at all 3 mice, 100 % transplantable ability was achieved. Measured s. c. tumor nodules of the studied melanomas grew with various dynamics, in case of mel Ibr/BRAF+ without malignant progressive, during of 3 weeks after tumor inoculation a volume of solid tumor nodule was only 120 mm3. In case of subclone mel Ibr EE/BRAF+ of 1st passage at the short latent period (5 days) gave the tumor nodules which are progressively increasing to more 20-fold size with steady exponential study. Conclusion. Adaptation characteristics to the in vivo growth are absent at the mel Ibr/BRAF+ line and are brightly expressed for cells of a subclone of mel Ibr EE/BRAF+ that testifies to its suitability for receiving a solid tumor at Balb/c nude mice without preliminary browning on mice. The received model can be recommended for assessment of effectiveness of multiple cytostatic therapy, including for BRAF-V600E mutation.
66-73 356
Abstract
Introduction. Autophagy, a catabolic process of protein and organelle recycling by transferring defective cytoplasm and organelles into double-membraned vesicles to degrade and regenerate materials, plays a critical role in maintaining energy homeostasis. Autophagy also protects against stress and infection, participates at the development of autoimmune disease. In recent years, the existence of alternative blood circulation system in tumors, vasculogenic mimicry (VM), which can partially compensate the lack of nutrients and oxygen under the hypoxic conditions, has been described. Objective. To elucidate the relationship between autophagy and VM. Materials and methods. In this study we used 2D- and 3D-culturing of melanoma cells derived from surgical species of patients with disseminated melanoma, electrophoresis and western blot, knockdown of the genes by using small interfering RNA (siRNA), flow cytometry, fluorescence microscopy. Results. We detected the basal level autophagy by examining the expression of autophagy-specific protein (LC-3B) by flow cytometry and cellular immunofluorescence staining by monodancylcadaverine. Both assays are the markers of autophagy late stage. Here we show that the level of autophagy in melanoma cells mel P, participated in capillary-like structures (CLS) formation in matrigel, was considerably higher than in mel Me cells which do not involve in VM. To explore the function of autophagy in the ability of melanoma cells to form CLS 3-methyladenine (3-MA) or chloroquine - inhibitors of initiation and terminal stage of autophagy - were used. Both inhibitors reduced the ability of melanoma cells to engage in VM. The data obtained were confirmed by siRNA-mediated gene silencing of BECN1 involved in the initiation of autophagy and ATG5 gene which is considered to be a marker of late stage of autophagy. Knockdown of BECN1 or ATG5 in mel P melanoma cells reduced the level of protein Beclin-1 and Atg5 about 70-75 %, and suppressed CLS formation in matrigel. Melanoma cells with the ATG5 gene knockdown changed the shape but maintained the ability to migrate and recognize each other, the formation of CLS was not observed. Low molecular weight VM inhibitor LCS-1269, significantly reduced the basic level of autophagy. Conclusion. Our data indicate that autophagy participates in CLS formation, and inhibition of autophagy suppresses CLS formation. We suggest that autophagy plays a dual role in the survival and development of tumors: autophagy helps cancer cells against environment stress and provides a temporary survival pathway by promoting energy regeneration, autophagy also promotes VM formation which supplies nutrients and oxygen to less vascularized area of tumor.
74-81 764
Abstract
Introduction. In recent years, significant progress has been achieved in immunotherapy of tumors, however, little is known about the crosstalk between the tumor and the immune system. It seems reasonable to rise the question of patients treatment with PD-1 and its ligands blockers after chemotherapy. Objective. To investigate the expression of cell surface molecules PD-L1 and PD-L2 both at the mRNA and protein levels in human melanoma cell lines after exposure to «Aranoza, lyophilisate for preparation of solution for injections» (aranoza-lio), liposomal formulation of aranoza and «empty» liposomes without aranoza. Materials and methods. In this study we used 11 melanoma cell lines, 5 of which carried the BRAF mutation. In quantitative polymerase chain reaction in real time we investigated the level of PD-L1 and PD-L2 gene expression. Using flow cytometry we evaluated the expression of cell surface antigens PD-L1 and PD-L2. Results. PD-L1 and PD-L2 mRNA are expressed at a lower level in cells with BRAF mutations, differences were significant only for PD-L2 (p = 0.1373 andp = 0.0207respectively). A high basal level of protein PD-L1 and PD-L2 expression was observed in wild type BRAF melanoma cells. After exposure to liposomal aranoza the level of PD-L1 and PDL-2 mRNA expression was significantly reduced (p = 0.0004 and p = 0.0442 respectively) in compare to control non-treated cells. It is of interest, aranoza-lio and «empty» liposomes increased the expression of PD-L1 (p <0.0001 and p = 0.0005 respectively) and PDL2 (p = 0.0005 and p = 0.0025). Of note, we observed an opposite effect in some melanoma cell lines. Moreover, changes in the expression of proteins PD-L1 and PD-L2 did not correlate with the mRNA level. The expression of PD-L1 protein after incubation with the liposomal aranoza increased dramatically compared to non-treated cells (p = 0.0269). Aranoza-lio and «empty» liposomes decreased the expression of PD-L1 protein (p = 0.0663 and p = 0.7213 respectively). The protein level of PD-L2 after exposure to liposomal aranoza did not change significantly (p = 0.1141), however, aranoza-lio and «empty» liposomes reduced the expression of PD-L2 (p = 0.0021 andp = 0.008). Conclusion. These findings are consistent with those of other researchers and confirm that the level of PD-L1 and PD-L2 mRNA and protein are modulated after treatment. Also, various drug formulations of Aranoza, as well as the «empty» liposomes, have different effects on the expression of PD-L1 and PD-L2 mRNA and proteins.
N. V. Pashintseva,
L. S. Eremina,
K. V. Lisitskaya,
A. V. Ivanov,
L. I. Kovalev,
M. A. Kovaleva,
S. S. Shishkin
82-90 347
Abstract
Introduction. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP А1) and other RNA-binding proteins involved in splicing participate in realization of genetic information and can be greatly changed in pathological conditions including tumors. Objective. Proteomic study of hnRNP A1 and other RNA-binding splicing proteins in 10 human malignant and non-malignant cultured cell lines of mesenchymal and epithelial origin. Materials and methods. Two-dimensional gel electrophoresis of adenocarcinomas (LNCaP, DU-145, PC-3, 769-P) and sarcomas (U2-OS, SK-UT-1B, RD) cell lines with following protein identification by matrix-assisted laser desorption ionization mass spectrometry have been carried out. Results. HnRNP А1 has been identified as an abundant protein in all studied malignant cell lines. It has been revealed in lower amount in normal mesenchymal cells compared to malignant cultured cells and achieved undetectable levels in myoblasts after induction of differentiation. Conclusion. High cellular level of hnRNP А1 can suggest high proliferative activity of cells including malignant those. Hence, hnRNP А1 and other RNA-binding splicing proteins hold promise to its further investigation in human transformed cells.
91-96 412
Abstract
Introduction. Treatment with interferon alpha (IFN-α) is a possible therapeutic option in patients with metastatic renal cell carcinoma (mRCC) with favorable and intermediate prognosis. However, in some patients there is a lack of clinical effect despite the activation of the cellular component of anti-tumor immunity. According to various authors the CD4+CD25+ suppressor cells may suppress antitumor immune response, and their study is of scientific interest. Increasing the number of these cells in the peripheral blood was found at various malignancies. Objective. To study the efficiency and tolerance of IFN-α in patients with mRCC and to examine changes in subpopulation of CD4+CD25+ T-lymphocytes and their association with the efficiency of the therapy. Materials and methods. Forty-one patients with mRCC received IFN-α in 2011 to 2016. Therapy was performed in the 1st line in 32 patients and in the 2nd line in 9 patients. Evaluation of immunological parameters was carried out within 1 week prior to immunotherapy, 2 weeks after the beginning and after 8 weeks in the control examination period. The immunophenotype of lymphocytes was assessed by multi-color flow cytometry using antibodies, including CD3, CD4, CD8, CD16, CD20, CD25 and perforin. Statistical analysis and data processing was performed using STATISTICA program (version 13). Results. The complete effect was achieved in 2 (4.8 %) patients, partial regressions were recorded in 9 (21.9 %) patients, and long (≥6 months) stabilizations of a tumor process were observed in other 19 (46.3 %) patients. The overall rate of disease control (complete + partial regressions + long stabilizations) was 73.1 %. The median time to progression was 8 months (p = 0.03). The baseline count of CD4+CD25+ T-lymphocytes in patients with an objective response was almost within the donor group (3.5 ± 2.1 %) and amounted to 4.4 ± 3.0 % (p <0.05). The baseline count of this subpopulation of cells was thrice greater in patients with the progressive disease: 12.1 ± 8.0 %. It should be noted a tendency to reduce this count during therapy in the group with clinical effect. Conclusion. The baseline count of subpopulations of CD4+CD25+ T-lymphocytes in the peripheral blood of patients can be a negative prognostic factor in immunotherapy IFN-α, most likely due to immunoregulatory subpopulations of CD4+CD25+FOXP3+CD-127bw-T-cells (Treg). It is advisable to further study this subpopulation of T-cells as a potential marker of the effectiveness of immunotherapeutic approaches.
97-102 344
Abstract
Introduction. The perspective direction in therapy of dyslipidemia (DLP) is a complex application of biologycally active substances from marine hydrobionts. Objective. The purpose of research - to compare the lipidcorrective action of preparates based on biologically active substances from marine hydrobionts - fukolam and maristim - individually and in combination with atorvastatin in patients with DLP. Materials and methods. 250patients with DLP and 40 healthy donors were included in research. As medicines atorvastatin, fukolam, maristim were used. In the blood serum the levels of lipid spectrum were determined. Results. Hypolipidemic action of fukolam in complex of basic therapy of patients with DLP was implemented by gradually reducing the total cholesterol, cholesterol of low-density lipoproteins, triglycerides levels to control values. The efficacy of fukolam was comparable with that of atorvastatin in a daily dose of 10 mg. Complex of «fukolam-maristim» showed hypolipidemic effect in severe hyperlipidemia. Conclusions. Combined therapy with use of bioactive substances of natural origin may be one of the way to improve the efficiency of hypolipidemic therapy. We have developed the algorithm of differential correction of DLP by inclusion the fukolam and maristim in complex therapy.
ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)
ISSN 1726-9792 (Online)