Preoperative blood markers for prediction of recurrence-free survival after surgical treatment of patients with stage III lung adenocarcinoma.

The possibility of the preoperative level of 42 indicators characterizing the cellular composition and metabolism in blood of patients with stage III lung adenocarcinoma (AC) to predict their relapse-free survival was studied. Blood samples of 451 patients with newly diagnosed AK stage III after their surgical treatment (resection volume - R0) have been investigated. The duration of the relapse-free period (period of observation - 1 year), cellular composition of the blood, concentration of C-RP, albumin, Cyfra 21-1 antigens, SCC, TPA, chemokines CXCL5, CXCL8, pyruvate kinase TuM2 PK isoenzyme, HIF-1α and hyaluronic acid in blood serum so as the proportion of blood cells with CXCR1 and CXCR2, CD44V6 receptors in blood serum were measured. To determine the dependence of the duration of the relapse-free period after the treatment on the observation time, Kaplan-Meier graphs were built. The relationship between the determined parameters and survival was judged using single- and multi-factor Cox proportional hazard models. Comparison of groups with different risk of AK recurrence was performed using the Log Rank test and χ2. The assessment of the predictive information content of laboratory tests was carried out using ROC analysis. It was shown that the concentration of monocytes, eosinophilic leukocytes, the relative quantity of lymphocytes with CXCR1 receptor, the level of Cyfra 21-1 before surgical treatment were associated with the duration of the relapse-free period. A regression equation was compiled, which included the level of Cyfra 21-1, relative content of lymphocytes with CXCR1, and the eosinophilic leukocytes / monocytes ratio. Based on the threshold value Y=0,597, a Kaplan-Meier plot of patient survival was built and the results of it correspond to the TNM stratification. The prognostic sensitivity of the results of the equation - 85,7%, the specificity - 94,7%.

On the issue of diagnostic value of determining the level of receptors and their ligands in blood in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) occupies the first place in the structure of mortality due to oncological diseases. Late diagnosis worsens the effectiveness of its treatment. There are no informative biomarkers that allow us to judge the prevalence of the tumor process, especially in the early stages of NSCLC. To determine the level of CXCL5, CXCL8, CXCR1 and CXCR2 in the peripheral blood of patients with NSCLC to assess the possibility of their use in the diagnosis of the disease. The material was the blood of 218 patients with NSCLC, 19 patients with lung hamartoma and 42 healthy people. The concentration of CXCL5, CXCL8, and SCC in blood serum was determined by enzyme immunoassay, the CYFRA 21-1 level was determined by immunochemiluminescence analysis. The proportion of leukocytes equipped with CXCR1 and CXCR2 receptors and the fluorescence intensity of receptor complexes with antibodies (MFI) in them were measured by flow cytometry. MFI CXCR1 in granulocytes and the proportion of lymphocytes supplied CXCR2, increased in the blood already at stage I of NSCLC and showed an even more significant increase in subsequent stages. The level of these indicators was correlatively related to the stages and characteristics of NSCLC. Measuring the level of MFI CXCR1 in the blood serum makes it possible to diagnose the early stages of NSCLC with a sensitivity of 87.4% (specificity - 73.8%). Determination of the proportion of lymphocytes equipped with CXCR2 demonstrates comparable diagnostic sensitivity (87.2%) and specificity of 66.7% in the detection of stages I-II of NSCLC. MFI CXCR1 in granulocytes can also be used to differentiate stages I and II of NSCLC (diagnostic sensitivity - 75,3%, specificity - 69,6%). The sensitivity of determining for this purpose the proportion of lymphocytes equipped with CXCR2 is 75.0% with a specificity of 71.7%. In 89.7% of patients with stages III-IV NSCLC, the MFI CXCR1 in granulocytes exceeds the threshold value of 47.8 (specificity - 74.8%). Diagnostic sensitivity of determining the proportion of lymphocytes for this purpose was 90.7%.

[Diagnostic efficiency of determining CXCR1, CXCR2 and hyaluronic acid blood level in non-small cell lung cancer patients]. / Diagnosticheskaia éffektivnost' opredeleniia urovnia retseptorov CXCR1, CXCR2 i gialuronovoi kisloty v krovi pri nemelkokletochnom rake legkogo.

In the structure of lung cancer incidence most cases belong to non-small cell lung cancer (NSCLC) which is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). A five-year survival rate of patients with stage I NSCLC is two times higher than in patients with stage II and more than five times higher than in stages III-IV. Currently, there are no informative blood biomarkers to diagnose early stages of NSCLC. The aim of the study was to evaluate complex determination of hyaluronic acid (HA), CXCR2 and CXCR1 levels blood of patients with AC and SCC. Blood samples from of 107 patients with SCC, 90 patients with AC, and 40 healthy people were used in this study. Concentration of HA in blood serum was determined by enzyme linked immunoassay. The level of CXCR2 and CXCR1 was determined by flow cytometry. Diagnostic parameters were determined by constructing mathematical models in the form of regression equations using the method of stepwise inclusion of predictors and subsequent ROC-analysis. Results of the study indicate that MFI CXCR1 in granulocytes, proportion of lymphocytes containing CXCR2 and concentration of HA in blood serum in stage I AC and SCC are significantly higher than in healthy people. The level of these parameter significantly increases at stage II of the disease compared to stage I and demonstrates further growth at its later stages. Based on the obtained results, regression equations were created: (i) including MFI CXCR1 in granulocytes, proportion of lymphocytes supplied with CXCR2 and HA concentration in the serum to detect stages I-II SCC (diagnostic sensitivity - 95.7%, specificity - 93.7%, threshold value - 0.59) and stages III-IV SCC (diagnostic sensitivity - 93.1%, specificity - 93.3%, threshold value - 0.64); (ii) including the proportion of lymphocytes supplied with CXCR2 MFI CXCR1 in granulocytes and CYFRA 21-1 blood level, which allows the detection of I-II stages of AC (sensitivity - 91.3%, specificity - 94.7%, threshold value - 0.61); (iii) including the proportion of lymphocytes supplied with CXCR2 and CYFRA 21-1 blood level, which allows the detection of AC stages III-IV (sensitivity - 94.6%, specificity - 91.3%, threshold value - 0.15); (iv) including the proportion of lymphocytes supplied with CXCR2 and HA level in the serum to differentiate stage II SCC from stage I (sensitivity - 94.4%, specificity - 87.5%, threshold value - 0.44) and II stage AC from stage I (sensitivity - 88.5%, specificity - 91.2%, threshold value - 0.46).

[Glutathione-dependent regulation of platelet aggregation with neutrophils and tumor cells].

It is shown that in the presence of reduced glutathione at low concentrations (1-5 microM) the extent of platelet aggregation with neutrophils increases and the lag period of platelet aggregation induced by tumor cells decreases. At the same time in the presence of reduced glutathione at high concentration (3 mM) the extent of platelet aggregation with neutrophils decreases, and the lag period of platelet aggregation induced by tumor cells increases. It is established that glutathione-dependent regulation of the intercellular contact formation between platelets and neutrophils depends on the ratio of glutathione oxidized and reduced forms: at fixed total glutathione concentration of 5 microM, increase of glutathione redox potential from -175 mV to 0 mV led to reduction in platelet aggregation with neutrophils. Thus, it is shown for the first time, that GSH has priming effect on the platelet aggregation with neutrophils and tumor cells, which may contribute to the regulation of inflammatory diseases and cancer.

[Evaluation of the double bonds of lipid fatty acids by ozonization in cancer patients].

The diagnostic value of total unsaturation of plasma lipids was studied by ozonization in 950 patients with malignant neoplasms. An examination was made on their primary admission. The control group included 470 patients with chronic benign diseases of the studied sites and 205 clinically healthy persons. The study established that the development of a tumor in cancer patients was associated with the structural changes in lipids, which are responsible for a significant reduction in their total unsaturation. The degree of lipid metabolic disturbances depends on the site of a tumor. The most significant disturbances were noted in patients with cancer of the stomach and urinary bladder. The calculated diagnostic criteria of double bonds (DB) corroborate the advisability of determining lipid unsaturation to improve the quality of diagnosis and monitoring of cancer diseases. The loose correlation between DB, lipid peroxidation products, the antioxidant system, and the electron paramagnetic resonance parameter a of spin-labeled serum is a prerequisite for their combined use in order to enhance the efficiency of laboratory diagnosis.

Oxidative metabolism of rat blood in the course of alveolar hepatic carcinoma PC-1 growth.

AIM: To evaluate oxidative metabolism of rat blood in the course of alveolar hepatic cancer growth in vivo. METHODS: The oxidation imbalance was assessed by the rise in the values of the integral index of oxidation stress. The structural and functional state of erythrocyte membranes was investigated by spin electron paramagnetic resonance spectroscopy. RESULTS: The growth of alveolar carcinoma was found to be associated with intensification of lipid peroxidation processes with increased blood content of conjugated dienes, malonic dialdehyde against the background of decreased concentration of endogenous antioxidants tocopherol and retinol. Destabilization of the structural state of erythrocyte membranes of rat tumor hosts at the development of oxidation stress was studied, which was characterized by nonspecific structural changes of membrane sorption centres, reduction in specific capacity in the protein-lipid contact area and its increase in the phospholipid bilayer, rise in the degree of order and polarity. CONCLUSION: Alveolar carcinoma growth in rats resulted in intensification of free radical lipid peroxidation processes with a shift of the prooxidant-antioxidant balance to the left and development of oxidation stress.

[Radionuclide studies on the hormonal manifestations of heat stress in cancer patients under controlled total hyperthermia]. / Radionuklidnye issledovaniia gormonal'nykh proiavlenii teplovogo stressa u onkologicheskikh bol'nykh pri obshchei upravliaemoi gipertermii.

The results of the investigations of ACTH, HGH, hydrocortisone, glucagon, C-peptide, insulin in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia treatment, aimed at increasing the range of indications for its use in clinical oncology.

[The prevention of the hypercoagulation syndrome during the combined treatment of lung cancer patients using artificial hyperglycemia]. / Profilaktika giperkoaguliatsionnogo sindroma pri kombinirovannom lechenii bol'nykh rakom legkogo s ispol'zovaniem iskusstvennoi giperglikemii.

Status of hemostasis system and occurrence of postoperative thromboembolic complications were assessed in 246 lung cancer patients in whom combined treatment included artificial hyperglycemia. The latter condition contributed to higher blood coagulability resulting in lung artery thromboembolism in some cases. Administration of a combination of heparin, curantil and nicotinic acid was followed by a decrease in blood coagulability, increase in anticoagulation function, decrease in platelet aggregability, activation of fibrinolysis and regression of biochemical signs of DIC syndrome thereby assuring a drop in the occurrence of thromboembolic complications.

[The effect of whole-body controlled hyperthermia on the energy resources of cancer patients]. / Vliianie obshchei upravliaemoi gipertermii na énergeticheskie resursy u onkologicheskikh bol'nykh.

The results of examination of 120 patients with advanced malignant melanoma, soft tissue sarcomas and lung and renal cancer suggest disturbance in mechanisms of energy supply during whole-body guided hyperthermia. Cell glucose uptake was inhibited in hyperglycemic patients. High energy loss in due to utilization of such alternative substrates as lipids and proteins which, in turn, potentiates peroxidation of lipids toxic to cell membranes. These data provide biochemical rationale for developing procedures aimed at managing biochemical dysbalance, increase in carbohydrate utilization included.

[Infusion therapy in sessions of general artificial hyperthermia using large doses of insulin in cancer patients]. / Infuzionnaia terapiia pri seansakh obshchei iskusstvennoi gipertermii s primeneniem bol'shikh doz insulina u onkologicheskikh bol'nykh.

A scheme of infusion correction of water-electrolyte shifts occurring during general artificial hyperthermia sessions (rectal t degrees-40-42 degrees C) employing large insulin doses (100-1120 U) in cancer patients has been suggested. The infusion therapy according to the technique described was used during 103 general artificial hyperthermia sessions in 58 patients. This made it possible to maintain physiologically normal blood plasma levels of glucose, Na+, K+, calcium, inorganic phosphates, normal acid-base balance, adequate hydration and circulating blood volume.

[Effects of induced hyperglycemia on the activity of pancreatic and gastrointestinal secretion of hormones in oncologic patients]. / Vliianie iskusstvennoi giperglikemii na aktivnost' pankreaticheskoi i gastrointestinal'noi sekretsii gormonov u onkologicheskikh bol'nykh.

Artificial hyperglycemia (AHG) used in the cancer treatment considerably increases the insulin and S-peptide content in blood, decreases the glucagon concentration and tissue glucose tolerance. The changes are reversible, have a functional character, that indicates the absence of a disbalance in hormonal mechanisms of carbohydrate metabolism control as well as marked disorders of the pancreas function. In order to achieve a wider range of indications for using AHG in complex schemes of the cancer treatment, it is necessary to take measures on optimization of the carbohydrate metabolism state which should be controlled by the suggested complex of laboratory tests.