[The radiosensitivity change after low-dose irradiation, possible mechanisms and regularities].

This paper is a short review of literature data and results of our own investigation into the adaptive response (AR). It was aimed at the analysis of the AR induction, its formation, some mechanisms, its expansion, and universality. It is supposed that a lot of mechanisms, a high variability degree, the absence of this phenomenon in some individuals, as well as dependence on many situations make the AR induction not predictable. Perhaps AR induction is not a universal phenomenon in practice, as it was supposed earlier.

[Are the properties of peripheral blood lymphocytes of patients with prostate cancer connected with the efficiency of radiation therapy?].

The genome damage (frequency of cells with micronuclei and chromosome aberrations), concentration of reactive oxygen forms (ROS), markers of lymphocytes activation, expression of proliferation (CD69, Ki67) and proapoptotic antigen (CD95), as well as the ability to adaptive response have been investigated in blood lymphocytes of healthy donors and patients with prostate gland cancer. The influence of hormone-therapy on lymphocytes properties and connection between the parameters studied with the effectiveness of treatment, which was estimated by the level of prostate specific antigen (PSA), have been investigated. It was discovered that the genome damage to the patients with prostate gland cancer lymphocytes does not differ from control. The increase of the ROS level and decrease of radiosensitivity (irradiation of isolated lymphocytes in vitro at a dose of 1 Gy) are observed but they are insignificant. The content of the cells expressing CD69 and CD95 markers doesn't change but the expression of proliferative activity marker Ki67 in cells decreases. Radiosensitivity of lymphocytes in patients with prostate gland cancer correlates with the CD95 markers expression--a higher radio sensitivity points to their predisposition to apoptotic death. The expression of the markers studied depends on the oxidative status--a high ROS level suppresses their expression. The hormone therapy applied before radiotherapy leads to the increase in radiosensitivity and decrease in ROS. As the MN test shows, the ability to adaptive response of the lymphocytes in patients with prostate gland cancer is increased as compared with lymphocytes of healthy donors but it is insignificant; moreover, hormones do not influence the ability to the adaptive response. The high oxidative status further the formation of the adaptive response. We suppose that the discovered correlation between the initial, before treatment, frequency of lymphocytes with micronuclei and treatment effectiveness, namely, the decreased number of damaged cells associated with the treatment efficiency, is very important for the treatment prognosis. The results obtained can be very important for the experimental justification and understanding a possible use of blood lymphocytes for the additional diagnostics of prostate gland cancer and prognosis for its successful treatment.

[Genomic damage, adaptive response induction in blood lymphocytes at the prostate cancer patients. Connection with the tumour radiotherapy efficiency].

On the blood lymphocytes of prostate cancer (PCa) patients before and during radiotherapy: DNA damage by DNA commet assay (DNA double strand breaks - DSB); the frequency of cells with micronuclei (MN) with cytokinetic cytochalasin block; the adaptive response induction by the additional irradiation of PHA stimulated lymphocytes in the doses of 0.05 and 1.0 Gy 24 h and 48 h after stimulation were studied. Changes of these parameters with the decreasing of prostate specific antigen (PSA) have been compared. PSA decreasing is an adequate of the radiotherapy efficiency. It was shown that in oncological patients the DSB level and the frequency of cells with MN have been increased. During radiotherapy (in 3 months) the DNA DSB level and the frequency of cells with MN is enhancing. The degree and direction change of these parameters coincide. It was discovered the significant correlations between the enhancing of DNA DSB level and the cell frequency with MN during therapy and degree of the PSA level decreasing. Then it was shown that when the cell frequency with MN before treatment is higher the radiotherapy efficiency is worse. These results can have great significance for the evaluation of the prognosis of the treatment efficiency. The investigation of lymphocytes for the adaptive response ability has shown that in the patients with the pronounced adaptive response before radiotherapy the decrease of PSA level during treatment was not significant (in mean 3.5-3.6 ng/ml); when the adaptive response is absent or the phenomenon of enhanced radiosensitivity was observed the PSA level (in the most cases) was decreased very essential (in mean 0.07 ng/ml). We can suppose that prognosis of the treatment efficiency of the prostate cancer patients with the pronounced adaptive response in blood lymphocytes will be worse.

[An estimation of individual radiosensitivity prostate malignant tumour cells using dynamic control of prostatic specific antigen level].

Individual radiosensitivity of prostate malignant tumor cells were estimated in blood of 122 patients in accordance with the level of prostate-specific antigen. Estimation has been performed in dynamics (before and after 3, 6, 12, 18, 24, 30 and 36 months) after radiation (external beam radiotherapy with total dose 70 Gy, brachytherapy with clinical dose 140-170 Gy) and hormone-radiation therapy. It was detected the differences of prostate tumors in the radioresistance. Levels of antigen at all times of detection in patients with relative radioresistant tumors (39 patients) were higher then in patients with radiosensitive tumors (81 patients). The number of persons with clinically unfavorable clinical prognosis in the group of patients with relative radioresistant tumors were registered 2 times more often then in group with radiosensitive timorous (35.9% vs. 16.0%). The ratio of patients with radiosensitive and relative radioresistant tumors depends on the method of treatment. It is supposed that after neoadjuvant hormone therapy tumour becomes more radiosensitive.

Use of the new levodopa agent Stalevo (levodopa/carbidopa/entacapone) in the treatment of Parkinson's disease in out-patient clinical practice (the START-M open trial).

Despite the significant symptomatic effects of levodopa, stable 24-h treatment responses are in the vast majority of patients replaced 2-3 years from the start of treatment by oscillations in motor symptoms (fluctuation, dyskinesia), amelioration of which requires addition of constant (physiological) stimulation of postsynaptic dopamine receptors. To some extent this is provided by Stalevo, which contains levodopa and two enzyme inhibitors: the DDC inhibitor carbidopa and the COMT inhibitor entacapone. The results obtained in the present study demonstrated the advantages of Stalevo over traditional agents in patients with the "wearing off" and "on-off" phenomena.

[The study on the assessment of the new levodopa drug--stalevo (levodopa/carbidopa/entacapone), in treatment of Parkinson's disease in out-patient clinical practice (the results of the open START-M)].

Despite significant symptomatic effect of levodopa, in most patients the stable 24 hour's effect changed for alterations of movement symptoms (fluctuations, dyskinesia) after 2-3 years of the therapy. These complications may be reduced due to the constant (physiologic) stimulation of post-synaptic dopamine receptors that, to a certain degree, provides the drug stalevo, which contains levodopa and 2 enzyme inhibitors, dopa decarboxylase (carbidopa) and catechol-O-methyltransferase (entacapone). The results of the study demonstrated beneficial effects of stalevo as compared to traditional therapy in patients with "wearing off" and "on-off" phenomena.