Metabolic reprogramming is a key feature driving oncogenesis in cancers.Recent studies have revealed that protein metabolism is largely altered in gliomas facilitating its malignant growth.Urea is the end product of nitrogen metabolism which is mainly produced by arginase.The interdependence of arginase and other biochemical mechanisms triggered scientific research interest.This research aimed to investigate the relationships between the urea as the main parameter of protein metabolism and glioma progression.It was also the most pronounced relationship between urea and the level of the nuclear protein Ki-67 as a marker of proliferative activity and O-6-methylguanine-DNA methyltransferase (MGMT), which performs DNA repair.Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed.

The aim of the study was to analyze the input of cytosolic and oxidative pathways of energy metabolism in ATP production of cultured cells by using FLIM and routine biochemical techniques. Fluorescent imaging of endogenous cofactors NADH and FAD demonstrated a more pronounced oxidative redox status of fibroblasts compared to tumor cells and significant differences in metabolic processes in which FAD is involved. Analysis of glucose and lactate content and absorption showed that tumor cells not only absorb glucose more intensively from the environment, but also use it more intensively during anaerobic glycolysis. Lower energy efficiency of glycolysis and FAD oxidative path and greater energy consumption is the reason for the lower concentration of ATP in tumor cells. Presumably, the prevalence of glycolytic metabolism in tumor cells could be largely determined by their hypoxic reprogramming through the PI3K/AKT/mTOR signal pathway. The results of the study suggest that correlation between intracellular consumption of glucose and cytosolic concentration of NADH may contribute to the characteristic of energy metabolism state of cultured cells and serve as the biosensor of malignant cell transformation.

Analysis of relationships between blood proteins content and free radical activity in blood plasma and tumor presence and stage was studied. Blood plasma samples of 39 patients with tumors of epithelial tissues previously non-exposed to anti-tumor treatment and 14 healthy patients without tumor (control sample) have been taken for analysis. Free radical activity was evaluated by induced biochemiluminescence and oxidative modification of proteins was estimated by the level of carbonyl derivatives. The content of blood plasma proteins and their fractions was determined by bioanalyzer. Blood investigation of patients with neoplasms revealed decrease in albumins and β-globulins, while the total plasma protein was not practically changed. Blood analysis in malignant tumors of epithelial tissues showed a significant increase in free radical activity and the degree of plasma proteins oxidative modification. In the initial stages of carcinogenesis processes of both fragmentation and aggregation of proteins predominate (growth of aldehyde and ketone carbonyl derivatives of dinitrophenylhydrazones). Protein aggregation dominates at the fourth stage of carcinogenesis (increase of aliphatic ketone-dinitrophenylhydrazones). Parameters of oxidative modification of blood plasma proteins can be used for preoperative diagnosis of the stage of malignant neoplasms of epithelial tissues.

Цель. Анализ электрофоретической подвижности эритроцитов у пациентов при заболеваниях, обусловленных нарушением пролиферации клеток, и её взаимосвязи с липидным спектром эритроцитарных мембран. Методы. Изучена кровь 42 больных злокачественными новообразованиями эпителиальных тканей (раком кишечника, почки, простаты, мочевого пузыря, шейки матки) и 16 больных дерматозами. Контрольную группу составили 20 практически здоровых человек. Электрофоретическую подвижность эритроцитов оценивали методом микроэлектрофореза. Содержание фракций липидов в эритроцитах определяли методом одномерной тонкослойной хроматографии. Результаты. У пациентов со злокачественными новообразованиями эпителиальных тканей и дерматозами, ассоциированными с нарушенными процессами клеточной пролиферации (псориазом), выявлено снижение электрофоретической подвижности эритроцитов на 59 и 60% соответственно (более чем в 2 раза), а при дерматозах воспалительного генеза снижение было менее выраженным (на 30%). Содержание заряженных фосфолипидов эритроцитарных мембран при онкологических заболеваниях и псориазе менялось сходным образом: статистически значимое снижение уровня сфингомиелинов при отсутствии отличий по содержанию фосфатидилэтаноламинов и фосфатидилхолинов. Выявлены разнонаправленные статистически значимые изменения в содержании лизофосфатидилхолинов в зависимости от стадии онкологического заболевания при их двукратном снижении при псориазе. Уровень холестерола, диацилглицеролов, свободных жирных кислот в мембранах эритроцитов при онкологических заболеваниях и псориазе менялся разнонаправлено. Вывод. При заболеваниях, обусловленных активацией клеточной пролиферации, электрофоретическая подвижность эритроцитов снижается более чем на 50%; меняющиеся при нарушениях фосфолипидного спектра мембран кинетические характеристики эритроцитов могут быть использованы для диагностики состояний патологической пролиферации, в том числе злокачественных новообразований.

Aim. To investigate the relationship between blood plasma biochemical indicators in patients with solid tumors before a treatment and after the first course of chemotherapy with objective treatment response. Methods. Blood plasma samples taken from 14 patients with cancer relapse were studied before the treatment and after the first course of specific chemotherapy (carboplatin, methotrexate, vinblastine in patients with urine bladder cancer and irinotecan, leukovorin and fluorouracil in patients with colorectal cancer). The first group included patients with colorectal cancer relapse (males — 3, females — 4) aged 57-62 years. The second group included patients with urine bladder cancer relapse (males — 5, females — 2) aged 48-64 years. Free radical activity and protein oxidative modification, as well as endogenous intoxication and major mineral and trace elements levels were studied. Results. When achieving the objective chemotherapy effect in patients after the first treatment course, an increase of alpha-1 globulin and gamma globulin level, as well as an increase of phosphorus, zinc, lithium and iron blood plasma level was observed. In case of following disease progression, the opposite dynamics of above-mentioned indicators was revealed. In patients with good objective effect of polychemotherapy after the first treatment course, a significant increase of endogenous intoxication and blood plasma free radical activity decrease were observed. If the following tumor progression was observed, the tendency of blood plasma free radical activity increase, accompanied by the total protein oxidative modification activation, was revealed after the first treatment course. Conclusion. The increase of alpha-1 and gamma globulin levels, as well as an increase of phosphorus level in blood plasma after the first course of polychemotherapy can be used as prognostic factors of anticancer therapy efficiency. High level of endogenous intoxication as well as an increase of copper, iron, zinc and lithium blood plasma concentrations can be applied as the additional markers.