Исследование проводилось на белых беспородных крысах. Метастазирование в печень моделировали путём введения клеток саркомы 45 (0,1 мл, 1*106) в селезёнку, за 3 недели выведенную под кожу. Изучали уровни рилизинг гормонов в гипоталамусе и тропных гормонов в гипофизе до развития первичной опухоли в селезёнке (через 1-2 недели после перевивки), в период сформированной первичной опухоли и до визуализации метастазов в печени (через 5 недель после перевивки). Установлено, что адаптационные реакции, разработанные для здорового организма, в условиях онкопатологии модифицируются с развитием нейроэндокринного диссонанса на центральном уровне гормональной регуляции, максимум - накануне метастазирования в печень. Ключевые слова: метастазы в печень, саркома 45, крысы, рилизинг-гормоны гипоталамуса, тропные гормоны гипофиза, адаптационные реакции.

Aim. To study the levels of reduced and oxidized glutathione (GSH and GSSG, respectively), as well as the thiol status in gastric cancer (GC) tumors of various histological types and grades. Materials and methods. The indicators were determined by ELISA methods in tumor, peritumoral and visually intact tissues obtained during surgery from 52 patients with GC: 18 patients had a G1-2 adenocarcinoma (AC), 8 with G3 AC, 6 with signet ring cell cancer (SRCC), 14 with combined gastric lesions (CGL) – AC with signet ring cell fragments, 6 with patients with a component of undifferentiated cancer, G4. Results. In the groups of patients with low-differentiated and undifferentiated tumors, the GSH content in the tumor tissue and the peritumoral zone was higher than in the group of patients with well- and moderately-differentiated tumors. Tumor GSH levels in G3 AC and SRCC exceeded the values in visually intact tissues. Moreover, in the visually intact tissue of patients with SRCC, GSH level was reduced relative to G1-2 AC and CGL. GSH in all tissues of patients with CGL was higher than in patients with G1-2 AC. The lowest level of GSSG in the tumor tissue was registered in SRCC: 27.5% lower than in G1-2 AC and 30.3% lower than in G3 AC. Patients with undifferentiated tumors (G4 AC) had the highest GSH content in all studied tissues: by 29.9% in tumor; by 40.7% in peritumoral zone; and in visually intact tissue not only GSH, but also GSSG was increased by 22.5–25.5% in comparison with AC G1-2. G4 AC was also characterized by a sharp increase in the thiol status in tumor tissues by 80.2 and 89.9% higher than in visually intact and peritumoral tissues, and it was statistically higher than in AC G1-2, AC G3, SRCC and CGL. The ratio of GSH and GSSG was the most informative. Conclusion . Poor AC differentiation (in the row G1-2, G3, G4) and a change of histological tumor type (AC, SPL and SRCC), i.e. an increase in tumor aggressiveness, were accompanied by the enhancement of reductive processes in tumor tissue, as evidenced by the statistically significant increase in the GSH/GSSG coefficient and a sharp increase in the thiol status in G4 AC.

Проведено исследование физико-химических параметров ассоциатов не стабилизированных наночастиц (НЧ) меди, полученных плазмохимическим способом. Для определения размеров ассоциатов НЧ использовали оптические методы, включая атомно-силовую микроскопию, спектрофотометрию и флюорометрию. Размеры НЧ меди варьировали от 30 до 75 нм, а размеры ассоциатов НЧ — от 481.1 до 1037 нм. Проведен анализ фазового состава НЧ меди методом рентгеновской дифрактометрии с использованием многофункционального рентгеновского дифрактометра Rigaku Ultima IV. На поверхности ассоциатов НЧ обнаружена оксидная пленка без примеси органических молекул. Изучали действие НЧ меди на культуру клеток А549. Обнаружено изменение биохимических показателей сыворотки крови белых беспородных мышей под влиянием НЧ меди. Выявлен противоопухолевый эффект НЧ меди и сопоставлена его выраженность при разных способах введения НЧ животным с фибросаркомой (С-45) и лимфосаркомой Плисса.

Purpose of the study. Examine the dynamics of the content of ferritin and other indicators of iron metabolism in the blood of patients with colorectal cancer before surgery and in the postoperative period to 7 days, and compare it with other known non-specific criteria of the acute phase of inflammation. Respond to the question whether changes in iron metabolism parameters in patients with colorectal cancer after surgery are specific. Materials and methods. The content of ferritin, transferrin, iron and unsaturated iron binding capacity (TIBC) in the blood serum of patients with colorectal cancer before surgery and in the postoperative period of 1, 3 and 7 days was determined at the biochemical analyzer Cobas Integra 400. The values of parameters in the group of individuals without cancer pathology (control group) were used for comparison. Results. Before surgery, patients studied parameters were within normal limits. In the postoperative period (7 days) ferritin level was significantly increased by 88%, and transferrin level was reduced by 73% in relation to that of the control group (p <0.05; U-Mann-Whitney). Total iron binding capacity was significantly reduced by 250%. Conclusions. Opposite changes of ferritin and transferrin, known as the acute-phase proteins, show predominance in the first week after surgery nonspecific reaction of patients to surgical stress. These metalloproteins are considered as one of the markers of the stress. We compared revealed changes in the studied parameters of iron system with the experimental data on the changes in the membrane potential of red blood cells and lymphocytes, and came to the conclusion that the identified synchronicity indicates their potential conditionality.

The analysis of the significance of a number of indicators characterizing the intensity of free-radical processes, the severity of oxidative stress, the degree of endogenous intoxication in the prediction and assessment of the effectiveness of treatment of patients with recurrent and metastatic cancer of the cervix. The obtained data are compared with the results of treating 27 patients with generalized cervical cancer. The method of cancer treatment includes a combination of autohemochemotherapy and autohemoimmunotherapy using cytokine series drugs: interleukin – 2 and interferon – alpha. Marked interrelation of the parameters studied with a degree of effect on tumor regression reflects the sensitivity of recurrent and metastatic cervical cancer to therapy. This allows the use of background levels of peroxynitrite and nitrosyl hemoglobin in assessing the effectiveness of the treatment.

Medium molecular weight molecules in blood of cervical cancer patients with and without metastases were studied to evaluate endotoxemia level. Efficiency concentration and reserve binding capacity of albumin were determined in cervical cancer patients with and without metastases in order to compare detoxifying capacity of their blood. Proteins’ sensitivity to proteolysis increased in cervical cancer patients with metastases. Changes in the physical and chemical properties, as well as decrease in functional activity of albumin, were found in all cervical cancer patients (in patients with metastases mostly) in comparison with donors. Coefficient of intoxication and toxicity index in cervical cancer patients with metastases and in remission were analyzed. Endogenous intoxication syndrome was more pronounced in cervical cancer patients with metastases than in patients without metastases.

The monitoring of patients with ovary cancer was implemented to evaluate effect of combined treatment the content of haptoglobin (the immunoturbidimetric technique applied) and oxydase activity of ceruloplasmin (the colorimetric technique applied). The comparison of obtained data with results of ultrasound monitoring and parameters of intratumoral hemodynamics of local recurrence was implemented. The reliable alterations of examined indicators were established under appearance of recurrence of ovary cancer and intensification of vascularization of recurrent tumor. The study established increased content of haptoglobin in patients with remission (as compared with its level in group of healthy women) and its significant increasing under expressed vascularization of recurrent tumor. The dynamics of level of haptoglobin corresponded to dynamics of ultrasound parameters of evaluation of effectiveness of treatment of recurrence. The alteration of ceruloplasmin activity was less expressed though it was detected at the earlier stage of recurrence in patients with avascular recurrence.

Changes in the blood and thymus of white rats with Pliss lymphosarcoma under pronounced antitumor effects of low-intensity modulated electromagnetic radiations of millimeter range (EHF EMR) were described. The factors were applied accordingly with the regimes of the activation therapy, with localization of action on the animal’s head. The treatment started 3 days before tumor transplantation and was carried out for 4 weeks. Specific antineoplastic agents were not used. Complete or partial tumor regression was noted in more than one third of the animals. The characteristics of morphofunctional state of the thymus, the parameters of white blood count, indicators of activity of lymphocyte dehydrogenases and intensity of free radical processes in the blood were evaluated. The antistress nature of changes in tumor-bearing rats under the effective actions of the factors was demonstrated. The possible connection between alterations of the studied parameters in animals with antitumor effect of different expressions with phasic processes in the immune system was discussed.

Настоящая статья посвящена исследованию влияния железа в наноформе (дисперсность частиц 30–50 нм) на процессы свободнорадикального окисления липидов в крови здоровых животных и животных с саркомой 45. Показано, что восьмикратное введение наночастиц в разовой дозе 1,25 мг/кг массы тела вызывало регрессию или торможение роста опухоли в 66,6 % случаев (у 12 животных из 18), причем интратуморальное введение оказалось эффективнее внутрибрюшинного: у двух третей животных рост опухоли был снижен в 4–7 раз по сравнению с контрольной группой, а у остальных животных наблюдалась полная резорбция опухолевого очага. У животных без опухоли введение наночастиц железа в указанных дозах не приводило к существенному изменению процессов перекисного окисления липидов и антирадикальной защиты. У животных с саркомой-45 происходило увеличение концентрации малонового диальдегида (МДА), вторичного продукта ПОЛ: в эритроцитах на 66 % (р < 0,05), в плазме крови на 141 % (р < 0,05), что указывало на усиление окислительных процессов. В группе животных, в которой наблюдался противоопухолевый эффект после введения наночастиц, выявлены нормализация содержания МДА и восстановление баланса антиоксидантных ферментов в эритроцитах, в плазме была показана активация антиоксидантных механизмов крови – увеличение активности каталазы (р < 0,05). У животных без эффекта был выявлен дисбаланс оксидантно-антиоксидантной системы в крови, что проявлялось в увеличении содержания МДА в эритроцитах, снижении активности церулоплазмина и максимальном значении МДА в плазме. Таким образом, изменение интенсивности окислительных процессов в крови животных-опухоленосителей, может способствовать развитию антибластомного эффекта при введении наночастиц железа.

The aim of this research was to study oxidative stress in red blood cells of the soft tissue sarcoma (STS) patients who underwent neoadjuvant chemotherapy (NACT). NACT method was combined with topical and systemic administration of cytotoxic drugs using autologous blood components for breeding drugs. The patients in main group were treated with NACT. The control group included STS patients who received surgical treatment alone. Content of malondialdehyde (MDA), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase were examined. There were significant increase of the MDA concentration, decreased SOD and CAT activities and compensatory enhancement of the glutathione-dependent enzymes activities in control group. These changes indicated that oxidative stress increased in the early postoperative period. After the NACT we observed a reliable normalization of the most studied parameters to the level of healthy donors. A 4-year follow-up of patients, who treated with NACT, showed that local recurrence and metastases of STS appeared in 5 out of 21 cases. The patients, who had not been treated with NACT, local recurrence and metastases of STS were showed in 12 out of 21 cases. In our opinion, reduction in the level of oxidative stress is one of the mechanisms responsible for the effectiveness of the proposed method.

Проведено комплексное лечение 50 больных колоректальным раком, включающее неоадъювантную полихимиотерапию (ПХТ) по схеме: оксалиплатин, 5-фторурацил, лейковорин дополнительно с препаратами, обладающими иммуномодулирующими (галавит) и антиоксидантными (мексидол) свойствами, и последующую радикальную операцию. Отмечено усиление свободнорадикальных процессов перекисного окисления липидов, что подтверждается увеличением интенсивности хемилюминесценции и накоплением молекулярного продукта малонового диальдегида на фоне снижения активности антиоксидантных ферментов первой линии защиты. По окончании курса ПХТ наблюдалось резкое увеличение интенсивности хемилюминесценции, содержание малонового диальдегида в эритроцитах снизилось, а в плазме – выросло, активность супероксиддисмутазы и церулоплазмина была снижена, активность каталазы в эритроцитах превысила фоновые значения, а в плазме достоверно не изменялась. В послеоперационном периоде у обследованных пациентов наблюдалась частичная или полная нормализация всех компонентов первой линии антиоксидантной защиты и системы глутатиона.

The fluorescence intensity of acridine orange (AO) dye bound to living human leukocytes, rat leukocytes, and Pliss lymphosarcoma cells of rat has been studied by fluorescence microscopy. The cell suspension of each test was divided into two parts, to one of which the drug cisplatin was added to a final concentration of 0.1 μg/mL and the mixture was incubated for 20 - 60 min. Acridine orange was then added and the average intensity of red and green fluorescence of cells was determined. The brightness of AO in the green region of the spectrum was reduced approximately 3-fold (p = 0.001) in cells with cisplatin. In the red region of the fluorescence, differences in the brightness of cells with and without cisplatin were not observed. These data indicate that a decrease in the brightness of green fluorescence of AO can be a test for the presence of cisplatin in cells.

A comparative study of the content of products of total oxidative modification of proteins and blood plasma lipids, as well as plasma chemiluminescence of cervical cancer patients with metastasis and in remission after therapy (combination, complex or chemoradiotherapy) was conducted. Results of the study of free-radical processes in cervical cancer patients imply intensification of lipid peroxidation and spontaneous oxidation of plasma blood proteins under the process of tumor progression.

The results of a comparative study of malondialdehyde (MDA) content, activity of antioxidant enzymes and indicators characterizing structural and functional state of membranes of erythrocytes in patients having advanced ovarian cancer (OC), who underwent therapeutic plasmapheresis before neoadjuvant polychemotherapy (PCT), and in patients with OC treated with chemotherapy treatment only, were presented. Oxidative stress and erythrocyte membrane fluidity increased on the second day after PCT in patients with OC treated with chemotherapy treatment only; redox processes decreased and dysfunction of erythrocyte membranes intensified one month after PCT. Plasmapheresis inclusion into the complex of cancer treatment contributed to the decrease of lipid peroxidation level, improvement of antioxidant defense in erythrocytes, stabilization of membranes of red blood cells on the second day after PCT and normalization of most of the studied parameters up to the level of healthy donors one month after the treatment.