Prognostic Significance of Tumor-Associated Inflammation in Renal Cell Carcinoma.

This study analyzed tumor-associated inflammation by assessing the expression of cyclophilin A (CypA) and TNF in samples of kidney tumors of various histological types. It was shown that different histological types of renal cell carcinoma differed by the expression of these proteins. Thus, the highest expression of CypA and TNF was observed in papillary and chromophobe kidney cancer, although no correlation with overall bacterial load was found for these tumors. In the case of clear cell renal cell carcinoma, the expression of proinflammatory factors was observed in only half of the cases and directly correlated with the presence of resident bacteria, serving as a favorable prognostic factor for the disease.

Soluble B7-H3 in Colorectal Cancer.

We present the results of comparative ELISA of the concentration of soluble form of immunity checkpoint B7-H3 (sB7-H3) in the serum of patients with colorectal cancer (CRC) at different stages before treatment and healthy control donors. The analysis revealed a statistically significant difference between the median levels of sB7-H3 in the blood serum of CRC patients (19.66 ng/ml) and healthy donors (16.76 ng/ml) (p=0.0025). ROC analysis showed 62.9% sensitivity and 56.7% specificity for CRC patients (cut-off 17.62 ng/ml; p=0.0028). An association of sB7-H3 levels with tumor progression was revealed. We demonstrated that sB7-H3 levels were significantly lower in patients with regional metastases than in patients without metastases (p=0.039) and that sB7-H3 concentration tends to decrease at the late stages of the disease. Thus, high serum level of sB7-H3 in CRC patients can be a favorable prognostic factor in future.

Clinical Significance of CD66b Expression in Non-Small Cell Lung Cancer.

We studied the expression of CD66b (a protein of the cancer-embryonic antigen family, expressed mainly in neutrophils) in tumor and stromal cells of non-small cell lung cancer (93 samples). The number of CD66b+ neutrophils is not associated with clinical and morphological parameters of the tumors and the disease prognosis. However, CD66b is expressed in the tumor cells of most studied samples. CD66b expression is also associated with the histological type of tumor and its localization. Increased expression of CD66b in tumor cells indicated a more favorable prognosis, which allows using this protein as a prognostic marker and as a potential target for the immunotherapy.

Cytotoxic Activity of Macrophages as a Tumor Malignancy Factor.

An experimental cell-based model was developed to study antibody-independent cytotoxic activity of macrophages that allows selection of derivative tumor cells resistant to this activity and clarification of the mechanisms responsible for this selection. Cytotoxic macrophages showing antibody-independent cytotoxic activity were obtained. Derivatives of PC3 and H1299 cells resistant to cytotoxic macrophage activity were generated. The main characteristics of the obtained derivative cells were studied. The proposed experimental model can be used as a tool for studying the mechanisms of the development of tumor cells resistance to antibody-independent cytotoxic activity of macrophages.

The Mechanism of the Development of Macrophage Tolerance in Tumor Microenvironment.

Bacteria forming the resident microbiome of the tumor are an integral component of its microenvironment. The interaction of the tumor microbiome with the tumor or tumor stromal cells is not well understood. We hypothesized that bacteria in the tumor microenvironment induce macrophage tolerance. Macrophage tolerance is a phenomenon of macrophage inability to respond to a repetitive inflammatory stimulus, which leads to a loss of cytotoxic activity. We studied the development of macrophage tolerance under the influence of bacteria and cytokines of the tumor microenvironment in vitro. It was found that the macrophage tolerance in the tumor stroma can develop in response to bacterial cell wall components and inflammatory factors. The acquired tolerance is inability of macrophages to produce proinflammatory cytokines TNFα, IL-1ß, and MCP-1 and activation of the production of immunosuppressive IL-10.

Transcriptome of Lung Cancer Cells Resistant to the Cytotoxic Activity of Macrophages.

The role of the immune system in tumor progression has been the subject of research for more than 100 years since Paul Ehrlich hypothesized that the presence of the immune system limits the occurrence of cancer. One of the mechanisms hindering the initiation and progression of the tumor is the cytotoxic activity of macrophages; however, in some cases, it is not sufficient to control tumorigenesis. This may be due to both the development of resistance of tumor cells to the antitumor activity of macrophages and the development of a tolerant phenotype of macrophages that do not have sufficient antitumor activity. In this work, the lung cancer cells resistant to the cytotoxic action of macrophages were obtained and characterized for the first time, and the genes associated with the observed changes were identified. Understanding the mechanisms of resistance of tumor cells to the cytotoxic activity of macrophages and the peculiarities of its manifestation in a tumor environment is critically important for improving the effectiveness of the existing methods of cancer treatment and developing novel methods for tumor immunotherapy.

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer.

A comprehensive analysis of the cell phenotype of the inflammatory infiltrate of the tumor stroma represents a promising area of molecular oncology. The study of not only soluble forms of various immunoregulatory molecules, but also their membrane-bound forms is also considered highly relevant. We performed a comprehensive analysis of tissue and circulating forms of the PD-1 and PD-L1 proteins, as well as macrophage and B-cell markers in the tumor stroma of gastric cancer, to assess their clinical and prognostic significance. The tumor and blood plasma samples from 63 gastric cancer patients were studied using ELISA and immunohistochemistry. Malignant gastric tumors were shown to be strongly infiltrated by B-cells, and their number was comparable to that of macrophages. For PU.1 expression, an association with tumor size was observed; i.e., larger tumors were characterized by fewer PU.1+ infiltrating cells (p = 0.005). No clinical significance was found for CD20 and CD163, but their numbers were higher at earlier stages of the disease and in the absence of metastases. It was also demonstrated that the PD-L1 content in tumor cells was not associated with the clinical and morphological characteristics of GC. At the same time, PD-L1 expression in tumor stromal cells was associated with the presence of distant metastases. The analysis of the prognostic significance of all the markers studied demonstrated that CD163 was statistically significantly associated with a poor prognosis for the disease (p = 0.019). In addition, PD-L1 expression in tumor cells tended to indicate a favorable prognosis (p = 0.122). The results obtained in this work indicate that the study of soluble and tissue markers of tumor stroma is promising in prognosticating the course of GC. The search for combinations of markers seems to be highly promising, with their comprehensive analysis capable of helping personalize advanced antitumor therapy.

Soluble B7-H3 in Ovarian Cancer and Its Predictive Value.

The content of the soluble form of protein of the key point of immunity B7-H3 (sB7-H3) in the blood plasma of 75 patients with epithelial ovarian cancer before treatment was measured by ELISA. It is known that B7-H3 belongs to the immunoglobulin superfamily (B7 molecule family) and is involved in the regulation of the immune response mediated by T cells. The sB7-H3 concentration correlated with the clinical and morphological parameters of ovarian cancer. The content of sB7-H3 was higher at the later stages of the disease, in the presence of ascites, and in patients with poorly differentiated ovarian cancer. It was revealed that increased plasma content of sB7-H3 in patients with epithelial ovarian cancer is associated with unfavorable prognosis of the disease. Therefore, sB7-H3 can be used as a prognostic marker in ovarian cancer patients.

Immunosuppression Factors PD-1, PD-L1, and IDO1 and Colorectal Cancer.

Due to the low efficiency of immunotherapy for colorectal cancer (CRC), it is extremely promising and relevant to study the mechanisms of immunosuppression. In this work, a comprehensive study of the expression of soluble and tissue forms of PD-1 and PD-L1 in blood serum and tumors of patients with CRC, as well as IDO1 in tumors was performed for the first time. The diagnostic and prognostic significance of the studied parameters was determined. A statistically significant decrease in the number of soluble forms of PD-1 and PD-L1 in the blood serum and the association of the number of PD-L1+ cells in the stroma of tumors with the CRC stage were established. The absence of correlations between soluble and tissue forms of the studied proteins was shown, indicating the presence of independent mechanisms of immunosuppression in CRC, which may explain the ineffectiveness of immunotherapy for this type of tumor.

Expression of Transcription Factor PU.1 in Stromal Cells as a Prognostic Marker in Non-Small Cell Lung Cancer.

Transcription factor PU.1 is involved in hematopoiesis and is expressed in various cells of the inflammatory infiltrate of the tumor stroma, mainly in macrophages. The expression of PU.1 in 100 samples of non-small cell lung cancer was analyzed by the immunohistochemical method. The number of PU.1+ cells did not correlate with clinical and morphological parameters of the tumors. However, increased number of PU.1+ cells significantly correlated with favorable prognosis in adenocarcinoma and poor prognosis in squamous cell carcinoma. Thus, transcription factor PU.1 can serve as a stromal prognostic marker of non-small cell lung cancer depending on the histological type of the tumor.

Soluble forms of immune checkpoints in ovarian cancer.

The data of a complex immunoassay comparative study of the content of soluble forms of sPD-1, sPD-L1, sNKG2D, sNKG2DL1, sB7-H3 and sHLA-G in the blood plasma of 75 patients with epithelial ovarian cancer and 20 healthy donors of the control group are presented. The diagnostic significance of the studied proteins was determined. The study showed that the profile of soluble immunity checkpoints differs when malignant ovarian pathology occurs. There was a statistically significant decrease in the content of sPD-L1, sNKG2DL1, sB7-H3, and sHLA-G in the blood plasma of patients compared with the control group. Differences were found in the content of the studied markers depending on the histological type of tumors. Correlations between the soluble forms of some of the studied proteins are shown, indicating the presence of independent mechanisms of immune regulation in ovarian cancer, which may explain the insufficient effectiveness of the existing immunotherapy for this type of tumor. The results obtained will undoubtedly facilitate the development of new effective methods for the diagnostics and therapy of ovarian cancer.

[Features of using endovascular laser coagulation in complex treatment of varicose disease].

The investigation was performed in 41 patients who were given laser coagulation of the subcutaneous vein trunks. The technique of laser coagulation as a stage of combined phlebectomy and the results of morphological investigation of the venous wall after laser coagulation depending on the parameters of coagulation are described. An analysis of the nearest and long-term results of the treatment using clinical and ultrasonic methods of investigation suggests that it is possible to use laser coagulation of the subcutaneous veins in patients with symptoms of chronic venous insufficiency of the II-V stages by CEAP classification.

[Effect of physical activity on spectral analysis indices of the heart rhythm in patients with stage II hypertension disease].

The authors aimed at studying wave structure of the heart rhythm of patients with II stage hypertension disease without and with physical activity. 72 patients with II stage hypertension disease (47 men and 33 women) have been observed. Investigators used national bicycle ergometer complex called VRR (Kiev, design office "Ergometr"). Indices of spectral analysis of the heart rhythm at rest and recovery period have been calculated. Bicycle ergometer diagnostic was carried out using continuously graduated increase of physical activity. Patients with II stage hypertension disease were found to have at rest the tendency to the increase of slow II grade waves and centralization index but indices of wave structure of heart rhythm at the period of recovery were not changed.

[Significance of ultrasound examination and computed tomography in the diagnosis of pancreatic cancer]. / Znachenie ul'trazvukovogo issledovaniia i komp'iuternoi tomografii v diagnostike raka podzheludochnoi zhelezy.

The diagnostic sensitivity of USI for localization of a tumor of the pancreatic head was 89.3%, specificity--69.7%, exactness--84.4%. When the tumor was localized in the body-tail these indices were 85.7%, 73.4% and 78.7% respectively. The sensitivity of CT in cases when the localization of the tumor was in the head of the pancreas was 84.9%, specificity--72.2%, exactness--76.5%. When the tumors were localized in the body-tail these indices were 89.5%, 75.4% and 80.9% respectively. An associated analysis of information of the ultrasound and CT concerning the structure of the pancreas made the exactness of the diagnosis of malignization as high as 87.6%, specificity as high as 81.3%, sensitivity as high as 93.7%. The informative value of USI and CT depended on the tumor size, the presence of an inflammatory reaction of the pancreas, the character of a complication, if any, or of their combinations, localization and size of the pathological focus. In the investigation no alterations in the pancreas characteristic only of cancer were found. Thus, a comparison of diagnostic potentials of USI and CT has shown that one method does not exclude, but only supplements the other. CT gives more reliable results in the assessment of the process spread to the surrounding tissues and regional lymph nodes, especially when the tumor is localized in the area of the pancreas tail. USI helps to make more exact assessment of the involvement in the process of the common bile duct, pancreatic duct, and of the visceral vessels by the Doppler examination.

[The evaluation of pharmacological tests with nitroglycerin, anaprilin, korinfar and No-Shpa in patients with stable stenocardia of effort]. / Otsenka farmakologicheskikh prob s nitroglitserinom, anaprilinom, korinfarom i no-shpoi u bol'nykh so stabil'noi stenokardiei napriazheniia.

Acute pharmacological tests were done in 47 patients with stable II-III functional class angina of effort. Indices for central hemodynamics were determined with the aid of Iu. T. Puskar' modification thoracic rheovasography techniques. In the acute test in patients with exertional angina, nitroglycerin, anaprilin, corinfar, and no-shpa tend to reduce energy expenditure on displacement of one litre of cardiac output, with corinfar being also capable of lowering total peripheral vascular resistance, no-shpa tending to augment the cardiac index and reduce total peripheral vascular resistance 30 minutes after the intake of the drug (but this effect is but of short duration: it lasts for only 30 minutes).

[An evaluation of the plastic function of the cardiomyocytes by silver staining of the nucleoli in patients operated on for ischemic heart disease]. / Otsenka plasticheskoi funktsii kardiomiotsitov metodom serebreniia iadryshek u operiruemykh bol'nykh ishemicheskoi bolezn'iu serdtsa.

Examinations of plastic function changes in myocardial cells (MC) from 36 patients with chronic ischemic heart disease were carried out before, during and soon after cardioplegic ischemia. The initial mean number of silver grains in nucleoli varied greatly showing some difference between groups of the patients with (9.5 +/- 0.48) or without (11.0 +/- 0.5) myocardial infarction. During the myocardial arrest this index of MC plastic activity was decreased in all but 7 patients. In contrast to this, it was elevated in most patients tested during subsequent reperfusion. On the basis of these data and parallel histochemical photometric assessment of DNA, RNA and succinate dehydrogenase activity, a hypothesis was suggested which explains the non-standard elevation of ribosomal cistron activity during both myocardial arrest and reperfusion by their compensatory reaction to myocardial injury.