The influence of 5-fluorouracil on activity of thymidine phosphorylase in gastric adenocarcinoma and normal adjacent tissue

The aim of the present study was to evaluate the change of thymidine phosphorylase (TP) activity in gastric adenocarcinoma and adjacent tissue upon the intraarterial administration of 5-fluorouracil (5-FU). Matherials and methods: The specimens of tumor and adjacent tissue were obtained by surgical operation on 36 patients (20 men and 16 women aged from 38 to 82 years) with gastric adenocarcinoma (stages II–IV). 5-FU was administered in the bolus dose to the gastroepiploic artery 2–60 min before the tumor resection. The concentration of 5-FU and activity of TP in both tissues were determined by high performance liquid chromatography method. Results: The concentration of 5-FU was decreased in a time-dependent manner in both tissues, though the interpatient variability of this value was much less in tumor tissue. The activity of TP was decreased with the course of the time after 5-FU administration in tumor and normal adjacent tissue. There were statistically significant differences in the TP activity in both tissues between 2–20 min and 40–60 min after 5-FU injection (p < 0.05). Conclusion: 5-FU administration results in the decrease of TP activity in tumor and normal adjacent tissues that might have importance for chemotherapy with fluoropyrimidines. Key Words: 5-fluorouracil, thymidine phosphorylase, gastric adenocarcinoma, normal mucosa

Применение метформина – целевая метаболическая терапия в онкологии

It is well known that metformin is widely used for the treatment of type II diabetes mellitus. However, in numerous epidemiological studies it was shown that patients taking metformin were less likely to have cancer of different localization and had better survival prognosis. Many researchers consider metformin to be a targeted metabolic drug that has many goals: it acts on mitochondria, affects intracellular signaling, blocks channels, inhibits the formation of endothelial and platelet growth factors, reduces the level of vitamins involved in the synthesis of nucleotides and amino acids, etc. It has also been established that metformin belongs to the group of “metabostemness” drugs, that is, it acts on cancer stem cells, blocking their division. We conducted a survey study that highlights the most important mechanisms and fields of application of metformin. The study of the use of this drug in oncology will make it possible to understand the pathogenetic targets of metabolic therapy and the prevention of cancer. Общеизвестно широкое применение метформина для лечения сахарного диабета II типа. Однако в многочисленных эпидемиологических исследованиях было показано, что больные, принимавшие метформин, реже болели раком различной локализации и имели лучший прогноз по выживаемости. Многие исследователи считают метформин таргетным метаболическим препаратом, который имеет множество целей: действует на митохондрии, влияет на внутриклеточный сигналинг, блокирует каналы, тормозит образование эндотелиального и тромбоцитарного факторов роста, снижает уровень витаминов, вовлеченных в синтез нуклеотидов и аминокислот и пр. Также установлено, что метформин относится к группе «метабостемных» препаратов, то есть действует на раковые стволовые клетки, блокируя их деление. Нами проведено обзорное исследование, которое освещает важнейшие механизмы и области применения метформина. Изучение применения данного препарата в онкологии позволит понять патогенетические мишени метаболической терапии и профилактики онкопатологий.

T9

Metformin is a antidiabetic drug with anticancer properties. However, the mechanism action by which metformin affects various cancer cells still unknown. It is known that tumor growth is accompanied by changes in the metabolic cascade that includes overproduction of lactate and adenosine. The adenosine is released into the extracellular environment and regulates differentiation, proliferation, and angiogenesis of tumor mass. We found that lactate is activator of key enzyme of adenosine metabolism – adenosine deaminase (ADA). Aim: The aim of our study was to investigate the catabolism of adenosine in the tumor while taking metformin. Materials and methods: In this study we investigated the level of adenosine, inosine, hypoxanthine and ADA activity in 15 women aged 46–76 years, with breast cancer (BC) T2-4N1M0 (cancer tissues) during treatment with metformin, 1000 mg per day for 3 months. Control group – 15 women aged 46–76 years, with stage T2-4N1M0 breast cancer (cancer tissues) without metformin therapy. Statistical analysis was performed using the license package StatSoft. Statistica 12.0. Results: ADA activity during treatment with metformin was 2-fold increased: 12.1 ± 2.49 nmol/min*mg in comparison with 4.77 ± 0.943 nmol/min*mg. Concentration of catabolic products of adenosine degradation was increased before metformin therapy. Inosine level was 0.121 ± 0.041 micro mol/g tissue (BC tissues from women without metformin 0.042 ± 0.015 micro mol/g tissue). Hypoxanthine 2.45 ± 0.428 micro mol/g tissue (in comparison with 0.711 ± 0.269 micro mol/g tissue). Whereas, adenosine level in BC after metformin therapy was 0.226 ± 0.148 micro mol/g tissue (in comparison with 0.186 ± 0.056 micro mol/g tissue), that were not significantly different. Conclusion: Thus, we have found that metformin significantly increases the rate of catabolism of adenosine, and this in turn reduces the inhibitory effect on the tumor microenvironment cytotoxic cells. Therefore, our data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to adenosine metabolism regulation

Контраст-індукована нефропатія (огляд літератури і власні дані)

This review shows the frequency of incidence of contrast-induced nephropathy in patients with ischemic heart disease who underwent percutaneous coronary intervention with intravascular administration of contrast media. The information about the pathogenesis, risk stratification and clinical manifestations of contrast-induced nephropathy is presented. Also, results of current completed studies about the possible therapeutic measures aimed at the prevention of this nephropathy are shown in this review.В данном обзоре представлены сведения о частоте развития контраст-индуцированной нефропатии у пациентов с ишемической болезнью сердца, которые подвергались чрескожному коронарному вмешательству с внутрисосудистым введением рентгеноконтрастных препаратов. Приведены данные о патогенезе, стратификации факторов риска и клинических проявлениях контраст-индуцированной нефропатии. Также отражены результаты выполненных на настоящий момент исследований о возможных лечебных мероприятиях, направленных на профилактику возникновения данной нефропатии.У даному огляді представлені відомості про частоту розвитку контраст-індукованої нефропатії у пацієнтів з ішемічною хворобою серця, які піддавалися черезшкірному коронарному втручанню з внутрішньосудинним уведенням рентгеноконтрастних препаратів. Наведено дані про патогенез, стратифікацію факторів ризику та клінічні прояви контраст-індукованої нефропатії. Також відображені результати виконаних на даний момент досліджень, про можливі лікувальні заходи, які спрямовані на профілактику виникнення даної нефропатії

THE RATE OF RENAL DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME AFTER USING X-RAY CONTRAST AGENTS

Purpose: to evaluate the rate and severity of filtration renal dysfunction in patients with acute coronary syndrome after percutaneous coronary intervention (PCI) with X-ray contrast.Materials and Methods: serum creatinine levels were collected from 71 patients twice, before the introduction of the contrast agent and 3 days.Resuls: in 56.9% of cases was recorded worsening renal function, and in 37.3% diagnosed the incidence of contrast-induced nephropathy (CIN), defined as a rise in serum creatinine level by 25% or more.Summary: because at the time of admission to the hospital, a physician still does not have enough reliable criteria for evaluating the risk of CIN, a preventive measures for improving renal function have to be included in the complex treatment of patients who are receiving the radiocontrast agent. Regardless of the severity of patients’ condition and the presence of concomitant chronic diseases

THE ROLE OF FREE RADICAL OXIDATION IN THE DEVELOPMENT OF CONTRAST-INDUCED DISORDERS OF RENAL FILTRATION

Aim. To find out the links between the state of system and the risk and severity of impairment of renal function in patients after percutaneous coronary intervention (PCI).Material and methods. The free radical oxidation system’s response was assessed in patients with different degree of severity of the glomerular filtration impairment. The intensity of lipid peroxidation was evaluated by the concentration of malondialdehyde (MDA) in the red blood cells of patients.Results. Almost all 59 patients after PCI were observed with various degree of inhibition of renal filtration. The mean value of MDA significantly (p = 0,032) increased from 10,3 ± 1,7 mmol/g to 11,0 ± 1,8 mmol/g. The level of MDA was significantly higher (p &lt;0,001) in the group of patients with more severe inhibition of glomerular filtration.Conclusion. The results indicate the important role of free radical processes in the pathogenesis of renal function impairment