[The risk-adaptive strategies of Hodgkin's lymphoma therapy].

Using of radiochemotherapy improves short-term and long-term results of treatment in patients with primary Hodgkin's lymphoma (HL) comparing with treatment by chemotherapy alone. The rates of 5-year, 10-year OS and DFS are 88%, 83% and 90%, 86% in case of radiochemotherapy, versus 73%, 66% and 72%, 68% using chemotherapy alone. The 5-year and 10-year OS, DFS estimates in treatment with ABVD are 84% and 83%, 75% and 74%; BEACOPP-baseline - 83% and 82%, 82% and 81% (p<0.05). At the same time ABVD chemotherapy develops less toxicity (p<0.001). The treatment with 6 cycles of ABVD is considered as the most appropriate in primary Hodgkin's lymphoma patients with extranodal lesions. Comparison of complications rate during chemotherapy with MOPP, ABVD, BEACOPP-baseline, BEACOPP-escalated reveals major hematologic toxicity and infectious complications rate in BEACOPP-escalated program (p<0,05). The age ≥45 years, hemoglobin <105g/l, B symptoms, fibrinogen >5g/l, involvement of 3 and more areas of lymph nodes, liver involvement, inguinal lymph nodes are defined by the multiple-factor analysis as adverse prognostic factors of patients with primary Hodgkin's lymphoma (HL) with extranodal lesions (p<0.05). Allocation of group of high risk is proved by correlation between survival and the Prognostic Score (PS). The 5-year and 10-year DFS, OS for patients with PS-0-2 estimates are 88% and 86%, 89% and 83%, for patients with PS-3-4 - 78% and 69%, 80% and 77%, for patients with PS-5-6 - 43% and 42%, 60% and 38% respectively (p<0.001).

Role of molecular-genetic abnormalities in pathogenesis and risk stratification of multiple myeloma.

Over the past decades the studies have greatly improved our understanding of the molecular basis of multiple myeloma (MM) and mechanisms of disease progression. The majority of the most widespread chromosomal aberrations, revealing in MM, has independent predictive value and influence on a choice of optimal treatment. There were observed 190 MM patients in hematologic hospitals of St. Petersburg. Genetic anomalies (GA) were detected at 3l,3% of patients and did not depend on their age. Patients with ISS III had a detectability of GA higher than with ISS II and ISS I (48,°% (24/5°), 2l,2% (7/33) and 27,6% (8/29)). Translocation t(ll;l4) was found in 23,3% (3O/129) patients; dell3q - 20,8% (27/13°); dell7p - at 8,4% (7/83); t(4;l4) - at 6,9% (9/13O), that allowed to stratify patients in groups of risk according to mSMART version l. O and 2. O. Median overall survival (OS) modified mSMART l. O in group of standard risk was 7° months, high risk - 47,l months. Median OS mSMART 2. O in group of standard risk was 7° months, intermediate risk - 47 months, high risk - 45 months. OS did not depend on age, clinical manifestations, treatment and other factors.

[The role of genetic polymorphisms of interleukins in chronic lymphocytic leukemia in patients of different ages].

Chronic lymphocytic leukemia (CLL) is a multifactorial disease, in which development the important role played the cytokine genes, in particular interleukins. This type of leukemia is more common in the elderly. The purpose of the study was to evaluate the association of genetic polymorphisms of interleukin with the development of chronic lymphocytic leukemia among residents of the Central Chernozem region of Russia. Genotyping of the -889C/T IL-1A, -590C/T IL-4 and VNTR IL-1 Ra was conducted in 206 patients with CLL and 307 individuals of the control group. The study found that the genetic risk factor for the development of CLL is allele -590T IL-4 (OR=-1,45). The development of thrombocytopenia in patients with CLL is associated with genetic variants -889T IL-1A (OR=1,95), -889TT IL-1A (OR=6,2) and IL-1Ra*1 (OR=-2,32).

[Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations].

AIM: To study the pattern of complex chromosome damages (CCD) in acute leukemias (AL) and their place in the development of post-transplant recurrences (PTR) of AL. MATERIALS AND METHODS: Cytogenetic and partially molecular biological studies of bone marrow cells were conducted in 10 patients with PTR. Of them, 6 patients were diagnosed as having acute lymphoblastic leukemia (ALL), including T-ALL and Ph-positive ALL in 2 and 4 patients, respectively; and 4 patients had acute non-lymphoblastic leukemia (ANLL), including one case secondarily induced by previous polychemotherapy (PCT) and irradiation. The standard G-band staining technique complemented by multicolor fluorescence in situ hybridization in one of the cases was used. RESULTS: It was shown that CCD had the similar pattern in 4 patients before transplantation and in PTR, progressed in 4 more patients, was absent or unnoticed in the early stage of the disease. The other recurrent chromosomal abnormalities that are worthy of notice are as follows: a) the presence of two Ph chromosomes in the cells of two of the 4 patients with Ph+ ALL; b) the frequent involvement of chromosome pairs 9, 19, 5, and 7 into the numerical and structural rearrangements. CONCLUSION: The important feature of PTR of AL is cellular CCDs, a portion of which is clearly related to previous PCT and may be of pathogenetic value for the development of recurrences.

[Lipid peroxidation and mechanism of antioxidant effect of vitamin E]. / Perekisnoe okislenie lipidov i mekhanizm antioksidantnogo deistviia vitamina E.

Data concerning lipid peroxidation and mechanism of the vitamin E inhibiting action are reviewed. Steps of initiated lipid autooxidation, formation of primary and secondary oxidation products, destabilizing the membrane structure and possessing cytotoxic effects are described. The mechanism of the antioxidant action of alpha-tocopherol, dependence of its activity on the structure and composition of the products of cooxidation of lipids and alpha-tocopherol in biological and model systems are also discussed.

[Participation of tocopherol and its analogs in lipid peroxidation processes and electron transport in rat liver mitochondria in vivo]. / Uchastie tokoferola i ego analogov v protsessakh perekisnogo okisleniialipidov i transporta élektronov v mitokhondriiakh pecheni krys in vivo.

The effects of vitamin E and its analogs--alpha-tocopheryl acetate with a shortened up to six carbon atoms side chain carrying a saturated and an unsaturated bonds at the chain terminus, alpha-tocopherol and alpha-tocopheryl quinone devoid of the side chain--on the rate of malonic dialdehyde formation, the diene conjugate and total lipid content in the liver as well as the activity of the respiratory chain enzymes--succinate--and NADH-dehydrogenase, succinate- and NADH-ubiquinone reductase, as well as the vitamin E and ubiquinone content in the liver mitochondria of vitamin E-deficient rats in vivo have been investigated. It has been found that alpha-tocopheryl acetate with a shortened (up to C6) side chain carrying a saturated bond at the chain terminus is the most effective analog of tocopherol. Further reduction of the tocopherol side chain or tocopherol conversion into quinone causes a decrease in their tocopherol activity.

[Interaction of vitamin E (alpha-tocopherol) with oxygenated fatty acid derivatives]. / Vzaimodeistvie vitamina E (alpha-tokoferola) s oksigenirovannymi proizvodnymi zhirnykh kislot.

Fluorescence spectra of alpha-tocopherol and its mixtures with oxygenated derivatives of fatty acids--linoleic acid hydroperoxide, hydroxylinoleic and ricinoleic acids--were investigated in terms of the excitation and emission dependence on the concentration of components in acetonitrile solution. In accordance with our results, formation of the alpha-tocopherol excimer and exciplex with the oxygen-containing derivatives of polyunsaturated fatty acids was suggested. The character of the interaction between components of the excited complexes and their possible role in peroxidation of lipids are discussed.

[Study of the interaction of alpha-tocopherol with phospholipids, fatty acids, and their oxygenated derivatives by (31)P-NMR spectroscopy]. / Izuchenie vzaimodeistviia alpha-tokoferola s fosfolipidami, zhirnymi kislotami i ikh oksigenirovannymi proizvodnymi metodom (31)P-IaMR- spektroskopii.

Interaction of alpha-tocopherol with phospholipids, oleic, ricinoleic acids and linoleic acid hydroperoxides was investigated by means of 31P NMR spectroscopy on a model artificial membranes containing egg phosphatidylcholine and lysophosphatidylcholine. alpha-Tocopherol was shown to support the bilayer organization of lysophospholipids, whereas its introduction into the lecithin-water system stimulated the hexagonal phase formation. Free fatty acids exhibited a synergism to alpha-tocopherol, the effect of the hexagonal phase formation being at most increased by oxygenated acids--ricinoleic acid and linoleic acid hydroperoxides. In accordance with the experimental data, a conclusion about modifying and structuring action of alpha-tocopherol was made. Origin of the alpha-tocopherol's modulating effect on the membrane structure and a possible role of hexagonal phase forming upon its action in the course of peroxidation of lipids was discussed.

[Mechanism of action of vitamin E. Study of the interaction of vitamin E (alpha-tocopherol) and its analogs with fatty acids and their derivatives by fluorimetry]. / K mekhanizmu deistviia vitamina E. Izuchenie vzaimodeistviia vitamina E (alpha-tocoferola) i ego analogov s zhirnymi kislotami i ikh proizvodnymi metodom fluorimetrii.

Formation of a complex between alpha-tocopherol or its analogues in the excited state and fatty acids or their hydroperoxides has been suggested basing on the fluorescence quenching experimental data. The possible mechanism of the complex formation, its nature and role in the fatty acid peroxidation is discussed.

[Transformation products of vitamin E and its analog--chroman C1 in an oxidizing ethyl linoleate medium]. / Produkty transformatsii vitamina E i ego analoga--chromana C1 v srede okisliaiushchegosiia étillinoleata.

Spirodimers, dimers, quinones of alpha-tocopherol and chroman C1 have been synthesized by the alpha-tocopherol and chroman Ci oxidation with K3[Fe(CN)6] and FeCl3. Products of the oxidative transformation of alpha-tocopherol and chroman Ci, viz. dimers, quinones and trimers, in the media of ethyllinoleate and nonane have been identified by HPLC, TLC, UV, IR and 1H NMR spectroscopy. The mechanism of the transformation and modifying activity of chromans under various oxidation conditions are discussed with regards to the experimental data.

[Role of isoprenoid chain of lateral mobility of alpha-tocopherol in lipid bilayer]. / Rol' izoprenoidnoi tsepi lateral'noi podvizhnosti alfa-tokoferola v lipidnom bisloe.

Using the quenching effect of the fluorescence by nitroxyl radicals the lateral mobility of chromanols in the lipid bilayer was studied. The lateral mobility of the chromanols was shown to increase when the length of phytol chain was diminished. The result is consistent with the idea that antioxidant affect of the chromanols depends on their lateral mobility.

[The effect of alpha-tocopherol in water-soluble form on human erythrocyte membranes while in contact with oxygen]. / Vliianie al'fa-tokoferola v vodorastvorimoi forme na membrany éritrotsitov cheloveka pri ikh kontakte s kislorodom.

The effect of water soluble tocopherol forms (dipotassium salt d,l-alpha-tocopheryl-phosphate) on lipid peroxidation induced by oxygen in membranes of human erythrocytes has been studied. An erythrocyte was considered as a structure reflecting the state of plasmatic membranes of organs and tissues. It has been established that this substance doses optimum for membrane protection against lipid peroxidation are not in excess of 1.5-5.0 mg per 1 kg of human body mass; the dose by an order higher may exert a toxic effect.

[Synthesis and antioxidative activity of structural analogs of vitamin E]. / Sintez i antiokislitel'naia aktivnost' strukturnykh analogov vitamina E.

Analogues of alpha-tocopherol with modified structure of side isoprenoid chain and chroman nucleus have been synthesised. The influence of chromanol structure on the dynamic of oxidation products formation have been investigated on models of induced and noninduced bulk-phase peroxidation of ethyl linoleate in presence of 2.3.10(-3)-1.2.10(-2) M alpha-tocopherol and the synthesised compounds.

[Nature of the modifying action of polyunsaturated fatty acids on the growth of transplantable tumors of different types]. / Kharakter modifitsiruiushchego deistvie polinenasyshchennykh zhirnykh kislot na rost perevivaemykh opukholei raznogo tipa.

Modification effect of sodium salts and ethers of linolenic, arachidonic and alpha-linolenic acids on the growth of transplantable mouse tumors was examined. Polyunsaturated fatty acids (PUFA) enhanced the growth of mammary adenocarcinoma Ca-755, whereas the opposite effect was observed in mice with leukemia L-1210 and sarcoma 180. No differences in the growth of melanoma B-16 and Lewis lung carcinoma were noted in control and experimental animals. Modification effect of PUFA was significantly suppressed by prostaglandin inhibitor indomethacin and to a lesser extent by antioxidant alpha-tocopherol.

[Use of high performance liquid chromatography of methylbenzocoumarin esters of prostaglandins in their quantitative fluorimetric analysis]. / Primenenie vysokoéffektivnoi zhidkostnoi khromatografii metilbenzkumarinovykh éfirov prostaglandinov dlia ikh kolichestvennogo fluorimetricheskogo analiza.

A method is suggested for quantitative fluorimetric analysis of natural prostaglandins (PGs). It is based on preparation of the fluorescent methylbenzocoumarine PG esters after their reaction with 4-bromomethyl-7.8-benzocoumarine (Br-MBC). Conditions for the reverse-phase high-performance liquid chromatography were evaluated, which permitted separating PGs into groups and according to the degree of unsaturation. Sensitivity and linear dependence of the ester fluorescence on the PG concentration make this method suitable for the quantitative analysis of PGs in different biological objects.