[ Spectrum of oncogene mutations is different in melanoma subtypes].

Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.

Use of recombinant interleukin-2 for intrapleural therapy of tumor-associated pleurisy.

Clinical efficiency of low dose Roncoleukin was studied in 30 patients with metastatic exudative pleurisy. Intrapleural therapy proved to be highly effective (overall effect reached 84%), was well tolerated, and improved patients' quality of life.

The lichen transplant methodology in the source apportionment of metal deposition around a copper smelter in the former mining town of Karabash, Russia.

The lichen transplant monitoring methodology has been tested for source apportionment of metal deposition around the Cu smelter and former mining town of Karabash. Transplants of the lichen Hypogymnia physodes (L.) Nyl., collected from a 'control' site in July 2001, were set up at 10 stations along a 60 km NE-SW transect centred on Karabash. Samples were collected after 2 and 3 month monitoring periods and analysed using established wet-chemical techniques. The sources of particulate investigated were the smelter blast furnace and converter, floatation tailings, metallurgical slags, local road dusts, top soils and ambient airborne total suspended particulate. From multi-element least-squares modelling the blast furnace was the main source of particulate in transplants close to the smelter (<10 km). Particulate from the converter, with relatively high Pb and Zn, was found to be more widely dispersed, being finer-grained and so having a longer atmospheric residence time. Ambient airborne particulate, sampled in Karabash town using air-pump apparatus, was almost entirely derived from the converter, very different to the lichen transplants from the same area which mainly contained blast furnace particulate. It is proposed that lichens close to the smelter mainly trapped larger blast furnace-derived particulate as they have a low capture efficiency for smaller (converter) particles. The study demonstrates the utility of lichen transplants for monitoring atmospheric deposition and highlights the caution required in their use to assess ambient air quality in human health studies.

[Cancer vaccinotherapy: from the experiment to clinical application].

Methods of cancer immunotherapy with dendritic cell-based vaccines, activated outside the organism, as well as techniques employing genetically modified whole-cell antitumoral vaccines, transfected by cytokine gens and stimulating the patient's dendritic cell stimulation in vivo, have been developed in Russian Oncological Research Center. Phase 1 clinical trials of dendritic cell vaccine in patients with disseminated melanoma and colon cancer have been carried out. The treatment is well-tolerated; significant adverse effects are absent. Moderate clinical efficacy and immune activation have been noted. Preclinical and phase 1 clinical studies of genetically modified vaccines also demonstrate the safety of this treatment and its ability to activate antitumoral immune response. Both vaccines are promising as subjects of rationally planned clinical trials of the efficacy of this treatment.

Biogeochemical signatures in the lichen Hypogymnia physodes in the mid Urals.

Multi-element content and uranium (U) isotopes were investigated in the lichen Hypogymnia physodes (native and transplants) sampled across a 60-km transect, centred on Karabash smelter town, from Turgoyak Lake (SW) to Kyshtym (NE) to investigate the origin of U. Kyshtym was the site of a major nuclear accident in 1957. (234)U/(238)U activity ratios in native thalli sampled during July 2001 were within the natural isotopic ratio in minerals. Uranium/thorium (U/Th) ratios were higher in native thalli towards the NE (average 0.73) than those in the SW (average 0.57). Element signatures in native thalli and transplants suggest U was derived from fossil fuel combustion from Karabash and sources lying further to the east. Systematic and significant U enrichment indicative of a nuclear fuel cycle source was not detected in any sample. Element signatures in epiphytic lichen transplants and native thalli provide a powerful method to evaluate U deposition.

[Melanoma cell lines as the basis for antitumor vaccine preparation].

The aim of the study was to obtain cell lines from tumor samples, and to determine phenotypic cell characteristics in order to choose the optimal line for vaccine preparation. 15 cell lines with stable growth, varying in cultural growth character and cytomorphology, were obtained from samples taken from patients with metastatic skin melanoma. Immunofluorescense method was used to determine the expression of T- and B-lymphocyte markers, antigens of major histocompatibility complex (MHC) class I and II, and CD86 co-stimulating molecule in the cell lines. The expression of melanocyte differentiation antigens and cancer/testicular antigens was evaluated using immunocytochemical assay. The results allowed the authors to distinguish three types of melanoma cell lines according to the expression of MHC molecules: MHC-negative; MHC class I positive; MHC classes I and II positive.

[Characteristics of drug resistance of tumor plasmocytes in vitro in patients with multiple myeloma differently responsive to chemotherapy]. / Kharakteristika lekarstvennoi ustoichivosti opukholevykh plazmotsitov in vitro u bol'nykh mnozhestvennoi mielomoi s razlichnym otvetom na khimioterapiiu.

AIM: To determine sensitivity of tumor plasmocytes in vitro to cytostatic drugs (prednisolone, alkeran belustin, vincristine, rubomycin, doxorubicin, cytarabin, methotrexate, cysplatin, etoposide). MATERIAL AND METHODS: The sensitivity was measured with DISC method in 12 patients with multiple myeloma (MM) in two groups: resistant and responsive to induction polychemotherapy (PCT). RESULTS: The groups appeared significantly different by lowering of pathological paraprotein concentration (PIg): by 7.4 +/- 2.5% and 32.5 +/- 3.7%, respectively (p < 0.05). The resistance to the drugs was higher in the resistant patients than in the responders (0.7 +/- 0.28 versus 0.4 +/- 0.02, p < 0.05). PCT schemes of resistant patients contained 65.0 +/- 2.3% of ineffective drugs. In the responders the percentage was 35.7 +/- 5.3% (p < 0.05). CONCLUSION: The relationship exists between resistance of tumor plasmocytes to drugs in vitro and clinical findings.

[A modern therapeutic strategy in Ph-positive chronic myeloleukemia]. / Strategiia sovremennoi terapii Ph-pozitivnogo khronicheskogo mieloleikoza.

The aim of this paper was to show the validity of programmed treatment of chronic myeloid leukemia (CML) patients regarding the risk group. In a group of low CML risk monochemotherapy (myelosan or hydroxyurea) was applied. In a group of moderate or high CML risk cytostatic therapy was performed in two variants: as monotherapy and polychemotherapy. Of 112 patients with CML, 50 received cytostatics plus long-term course of interferon-alpha. The combined treatment was well tolerated.

[Acute rheumocarditis in young men]. / Ostryi revmokardit u molodykh muzhchin.

A study was made of the characteristic features of rheumocarditis in 200 young recruits. Rheumocarditis developed within the first 2-3 days since the onset of migrating polyarthritis and high fever. In many cases, it was accompanied by rhythm and conduction disorders as well as by a moderate increase of the left heart in combination with intracardiac hemodynamic disturbances. In 42 patients (21%), myocardial injury was coupled with mitral valve lesion. Injury to the pericardium was recorded in 20 patients (10%); fibrinous pericarditis was diagnosed in 15 patients, exudative pericarditis in 5 patients. Injury to all 3 heart membranes was ascertained in 5 patients (2.5%) (according to echocardiography). Thus, the clinical and instrumental manifestations of rheumocarditis made it possible to diagnose marked carditis symptoms almost in all the patients (in 96%). Unmarked carditis was only discovered in 7 patients. The above-mentioned characteristics of rheumocarditis in young men may be due to the intensity of the action of streptococcal infection on the heart structures within the first days of the disease as well as due to the action of immunopathological processes. Besides, a definite role may be played by the foregoing physical load.

[Determination of antibodies to Streptococcus group A polysaccharide by an immunodiffusion method in human sera in various pathological processes of streptococcal etiology]. / Opredelenie antitel k polisakharidu streptokokka gruppy A metodom immunodiffuzii v syvorotkakh cheloveka pri razlichnykh patologicheskikh protsessakh streptokokkovoi étiologii.

A method for the assay of antibodies to the specific antigenic determinant of group A streptococcal polysaccharide (A-polysaccharide) in human sera was developed. The sera were tested in the precipitation test in agar gel with different doses of A-polysaccharide. The presence of a high level of the above-mentioned antibodies is indicative of infection caused by group A streptococcus, but not streptococci of other groups or by the L-forms of streptococci. In 87.5% of patients with primary rheumatism a high level of antibodies to the specific antigenic determinant of A-polysaccharide was detected during the first day of the disease, which confirms most convincingly the etiological role of group A streptococcus in rheumatism. Considerable differences in the level of antibodies to A-polysaccharide in the active and non-active phases of rheumatism have been established, which makes it possible to use the presence of a high level of these antibodies as an indicator of the rheumatic process activity. A considerable percentage of sera with a high level of antibodies to A-polysaccharide was also detected in erysipelas and acute glomerulonephritis patients.

[Antibodies to fibroblast antigens in the sera of rheumatism patients]. / Izuchenie antitel k antigenam fibroblastov v syvorotkakh bol'nykh revmatizmom.

The sera from patients with active rheumatic fever possess unmarked ability to react with antigens of human fibroblasts. More intense reactions were obtained with guinea-pig fibroblasts. In rheumatoid arthritis, positive reactions with human and guinea-pig fibroblasts were disclosed in half of the test sera. No complement-dependent cytotoxic antibodies were found in the patients' sera.