MODULATION OF ANTITUMOR IMMUNE RESPONSE IN MOUSE PROSTATE CANCER MODEL.

Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model. We studied their impact on murine prostate cancer cells and on dendritic cells (DC), the most potent antigen-presenting cells known. RM-1 is a murine prostate cancer cell line, resembling hormone-independent model, which is a lethal variant of this disease in humans. Dendritic cells were obtained from murine bone marrow. Cell proliferation assays were performed to evaluate the effect of 5-AzaC and lenalidomide on prostate cancer and DC. Flow cytometry, ELISA and real-time PCR was performed to evaluate the effect of these compounds on DC and prostate cancer cells. 5-AzaC treatment of RM-1 prostate cancer cells and DC resulted in the decreased proliferation for both, while lenalidomide had no effect. DC were treated with lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC. There was also the change in the expression of endothelin receptors on DC, which can affect their function. 5-AzaC also resulted in the increased expression of cancer-testis antigen, P1A, by prostate cancer cells. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide should increase tumor immunogenicity and it enhanced DC function. Therefore, these compounds might have a role in the treatment of advanced prostate cancer.

[Assessment of patients' condition by noninvasive methods of examination in the follow-up after Fontan's operation in atresia of the right atrioventricular ostium]. / Otsenka sostoianiia bol'nykh s pomoshch'iu neinvazivnykh metodov issledovaniia v otdalennye sroki posle operatsii Fontena pri atrezii pravogo atrioventrikuliarnogo otverstiia.

The article discusses the results of using noninvasive methods to study the condition of patients (20) in late-term periods after Fonten's operation in atresia of the right atrioventricular orifice. All patients were subjected to physical examination, electro-, phono- and echocardiography, radiological examination, radioisotope scintigraphy, and left ventriculography. Most patients change to functional class I in the late-term periods after the operation. Though the patients have a sense of well being, the left-ventricular pumping and contractile functions remain disturbed. A tendency towards gradual improvement of these parameters is noted, however. The right atrium is enlarged and its myocardium hypertrophied. Its overexertion increases significantly in physical loading. The blood flow in the lungs becomes normal gradually. The results of various noninvasive methods correlate with one another and with the results of angiocardiography. This allows in some cases to avoid intracardiac examination which presents a certain risk, especially in the first one-two years after Fonten's operation when the mechanisms of cardiac activity compensation are still weak.

[New approach to the selection of the method of corrective surgery in single heart ventricle]. / Novyi podkhod k vyboru metoda korrigiruiushchei operatsii pri edinstvennom zheludochke serdtsa.

The work deals with choice of the optimal method for correction of a single heart ventricle. With this in view, the authors studied the anatomy and function of the atrioventricular valves, the volumetric and functional characteristics of the single ventricle, and the condition of the central parts of the pulmonary artery and the subaortic tract in 46 patients with various anatomical forms of the anomaly. Analysis of the results not only helped in specifying the indications for the use of one or another method of correction of the single ventricle but made it possible to determine the optimal volume of the chosen method according to the anatomo-hemodynamic variant of the anomaly and the condition of the vessels of pulmonary circulation. By means of the approach discussed in the work, 4 operations were carried out for forming an artificial interventricular septum and 14 operations for hemodynamic correction in patients with stenosis of the pulmonary artery.

[Quantitative evaluation of normal mitral and tricuspid valves (comparison of the data of echocardiometric and morphometric studies)]. / Kolichestvennaia otsenka mitral'nogo i trekhstvorchatogo klapanov serdtsa v norme (sopostavlenie dannykh ékhokardiometricheskogo issledovaniia).

Fifteen children, aged 5 to 15 years, were investigated by two-dimensional echocardiography in order to estimate quantitative characteristics of the normal mitral valve (MV) and tricuspid valve (TV). The results were compared to morphometric data in 21 children matched for age. Echocardiography allowed a fairly accurate estimation of the dimensions of atrioventricular valves. Following the standardization procedure, echocardiometric findings showed good correlation to morphometric data, while the differences between the two never exceeded 23%. Quantitative MV and TV characteristics were dependent on body surface area, but, the dependence being nonlinear, the variation followed a strict pattern.

[Quantitative assessment of the aorta and pulmonary artery in normal subjects (comparison of data from echocardiometric and morphometric studies)]. / Kolichestvennaia otsenka aorty i legochnoi arterii v norme (sopostavlenie dannykh ékhokardiometricheskogo i morfometricheskogo issledovanii).

Fifteen children whose age ranged from 5 to 15 years were examined by the method of two-dimensional echocardiography to calculate the quantitative characteristics of a normal aorta and pulmonary artery. To determine the character of correlation of these data with the findings of morphometric examination of the heart, the results were compared with the morphometric data in 21 children of the same age. The study showed that echocardiography makes it possible to calculate the size of the semilunar valves quite precisely. In standardization of the echocardiometric examination the parameters correlate well with the findings of morphometry, while the differences between them do not exceed 6-7%. It proved that the quantitative characteristics of the aorta and pulmonary artery were determined by the body surface area, but due to the non-linearity of their dependence on it, they change according to strictly specific patterns.

[Regional blood circulation in the area of the hip joint in patients with various inflammatory rheumatic diseases]. / Regionarnoe krovoobrashchenie v oblasti tazobedrennykh sustavov u bol'nykh s nekotorymi vospalitel'nymi revmatologicheskimi zabolevaniiami.

An analysis of the results of a study of the regional blood circulation in 36 patients with marked pathology of the hip joints of inflammatory nature (rheumatoid arthritis, Bechterew's disease, Reiter's disease) showed a statistically significant increase in transcutaneous oxygen pressure in the projection of the affected joints in unilateral as well as in bilateral pathology. In unilateral pathology there was a significant increase in transcutaneous oxygen pressure, on the surface of the contralateral joint, where pathology was undetectable by routine clinical methods. In the authors' opinion, it could be indicative either of an early stage of the joint involvement or the general reaction of a region under study to an inflammatory process.

[Gangrene of the extremities in diabetes mellitus]. / Gangrena konechnostei u bol'nykh sakharnym diabetom.

The results of the treatment of 111 patients, who have developed obliterating diseases of the arteries of the lower extremities against the background of diabetes mellitus, are set forth. The author strongly recommends not to come hastily to amputation as an intense treatment may bring about a persistent remission of the pathological process even in senile patients.