The high incidence of recurrence and metastasizing in colorectal cancer (CRC) poses the challenge for the improvement in long-term treatment outcome.AIM:To determine the major indicators of redox-formative molecules in the tissue of metastatic CRC (mCRC), stages Т2-4N0-2M0G2-3, namely the rate of superoxide radical (SR) generation, nitric oxide (NO) content, the activity of matrix metalloproteinases (MMP), lactoferrin (LF) content, and "free" iron and their association with some clinical and pathological characteristics of the patients.MATERIALS AND METHODS:mCRC samples from 51 patients were analyzed (stage II, 31 patients; stage III, 20 patients). The LF and "free" iron were assessed by electron paramagnetic resonance (EPR) at the temperature of 77 °K. The rate of SR and NO generation was determined with spin traps (ТЕМРО-Н, diethyl dithiocarbamate). The activity of MMP-2 and -9 was measured by gelatin zymography using SDS-polyacrylamide gel electrophoresis. Ki-67 expression was analyzed by immunofluorescence technique.RESULTS:In tumors with metastases into the regional lymph nodes (N1-2 category), SR generation rate was 2.2-fold higher than in the tumors categorized as N0. In G3 mCRC, SR generation rate was 1.7-fold higher than in G2-tumors (p < 0.05). The rate of SR generation correlated inversely with differentiation grade of the tumor (r=-0.61; p < 0.05). MMP-2 and -9 activities in mCRC tissue correlated with SR generation rate and NO level (r = 0.44 ÷ 0.53, p < 0.05). The direct correlation between LF content and the stage of the disease (r = 0.42) and "free" iron content (r = 0.61) was demonstrated while the correlation between LF content and tumor differentiation grade was inverse (r = -0.57; p < 0.05).CONCLUSIONS:The altered tumor-associated redox state in mCRC tissue contributes to the increased cell proliferation and formation of aggressive phenotype of the tumor. The assays for the content of redox-formative components in mCRC may be used as additional prognostic markers of the course of the disease in CRC patients.
AIM To assess the inducible NO-synthase activity and the total RNase activity in tissue samples and blood neutrophils of the patients with prostate intraepithelial neoplasia (PIN) and prostate cancer (PCa) of different stages. MATERIALS AND METHODS NO level was measured in tumor tissue and neutrophils of patients with PIN and PCa of different stages by electron paramagnetic resonance using the spin traps technology. RNase activity in tumor tissue of patients with PIN and PCa was measured by the method of zymography. RESULTS We have found that NO levels in prostate tumor tissue were significantly higher than in the PIN and increased along with the disease progression. Analysis of NO level in neutrophils of the PCa patients demonstrated that the values were not dispersed and did not depend on the stage of disease. NO level in neutrophils of the PCa patients increased manifold as compared with that in healthy donors. At the same time, the RNase activity in the prostate tumor tissue gradually decreased with PCa progression. CONCLUSION Activities of inducible NO-synthase and RNases change significantly with progression of PCa.
An erbium-doped β -GaLaS 3 crystal has been grown by the solution-melt method, and the effect of γ -irradiation on their vibrational and radiative properties has been investigated. Experiments have demonstrated that the crystal is transparent in the near and mid-infrared (IR) regions (transparency ∼62% in the range of 350–7100 cm −1 ), which allows it to be used as an effective matrix for creating lasers in this spectral range. For the first time, the vibrational spectrum of the crystal and the density of phonon states have been calculated using the density-functional theory (DFT) method. Both the original and γ -irradiated β -GaLaS3:Er crystals were investigated by Raman and IR spectroscopy. It has been established that irradiation with a dose of up to 5000 Gray does not lead to structural changes in the crystals. The effect of the formed defects is more clearly manifested in the IR reflection spectra, compared to the Raman spectra. The mechanism of the occurrence of excited states and the emission of Er ions embedded in the lattice has been established, and the effect of γ -irradiation on the radiative properties of β -GaLaS 3 :Er due to the occurrence of radiation-induced defects has been analyzed. A model has been constructed that explains the Stokes and anti-Stokes radiation of the erbium ions in the crystal. It has been demonstrated that the grown crystal has good prospects for sensor and laser technology of the near and mid-IR ranges due to relatively high values of optical transparency and the intense radiative capacity of the erbium ions.
Summary. Aim: to investigate the levels of superoxide radical (SR) generation and matrix metalloproteinase activity in tumor and adipose tissue adjacent to the tumour (ATA) depending on BMI and menopausal status of breast cancer patients. Object and methods: tumor tissue samples and ATA (postoperative material) from 70 women with breast cancer were studied. The methods used were EPR spectrometry, polyacrylamide gel zymography, general clinical and statistical methods. Results: a significant difference (p < 0.05) in the rate of SR generation at normal weight and obesity was observed in postmenopausal patients, both in the tumour (1.6 times) and in the АТА (1.7 times); there is a significant difference (p < 0.05) in the total activity of MMP-2 and -9 at normal weight and obesity, both in the tumour (2.2 times) and in the АТА (1.9 times). In premenopausal patients with breast cancer with overweight and normal weight do not differ significantly in the frequency of distant metastasis and the overall survival. Рostmenopausal patients with obesity were characterized by a significant (p < 0.05) increase in the frequency of distant metastasis and a decrease in the overall survival. At levels of MMP-2 activity in the ATA above 2.8 units, patients had a significantly shorter life expectancy (p = 0.02) and a higher risk of adverse disease outcome (HR = 2.9) than at lower levels of enzyme activity. Conclusion: the results obtained indicate the prospects for further research and the possibility of using these factors of the tumour microenvironment (SR generation and MMP activity in tumor tissue and ATA) as effective markers of breast cancer prognosis in the presence of overweight.
Introduction. The study of volt-ampere characteristics (VAC) and galvanomagnetic properties of semiconductor materials and structures based on them under the action of microwave radiation and magnetic fields in a wide range of temperatures is an urgent task for the development of the element base of spintronics and supersensitive sensors.Problem Statement. Currently, there has been no precision complex of thermoregulated cryogenic equipment for low-temperature studies of VAC and galvanomagnetic properties of semiconductor materials and structures based on them in the field of the external magnet, which fully meets the needs of studying the parameters of su-perconducting materials.Purpose. The purpose of this research is to design and to manufacture a single computerized complex of ther-moregulated cryogenic equipment.Materials and methods. Based on the existing domestic experience of creating cryosystems for magneto-physical studies and accessories to them, the development and manufacture of a set of thermally regulated cryo-genic equipment for studying the volt-ampere characteristics and galvanomagnetic properties of semiconductor materials and structures based on cryostat with a specialized manipulator.Results. As a result of the research, we have created a complex of precision cryogenic equipment as a part of a cryosystem thermoregulated within 1,5-300 K, based on a helium continuous flow cryostat with a narrow shank. The system consists of an external magnet built into the interpolar space, a specialized manipulator having a built-in gauge for measuring the liquid helium level in the cryostat shaft, a temperature controller, modules for measuring the volt-ampere characteristics and galvanomagnetic properties of semiconductor materials, and software.Conclusions. The designed equipment has as good characteristics as the best western analogs and exceeds them in terms of cryoagent consumption and costs of its maintenance and service.
AIM:To study the levels of redox-forming molecules generated in tumor, adipose tissue (AT), neutrophils and platelets of patients with colorectal cancer (CRC) with normal body weight or obesity.MATERIALS AND METHODS:83 samples of tumor tissue and 83 samples of the AT taken at the distance of 5 cm from the tumor as well as 83 blood samples have been analyzed in the patients with CRC with metachronous lesions in liver. The comparison group consisted of 18 patients who were surgically treated for ulcer. The rates of free radical generation were measured by electron paramagnetic resonance.RESULTS:Free radical generation rate in tumor tissue and AT increased and nitrogen oxide (NO) levels decreased in patients with body mass index ≥ 25 kg/m2 as compared to the patients with normal body weight (p < 0.05). The superoxide generation activity in neutrophils of CRC patients exceeded about 7-fold the values obtained in neutrophils from patients with ulcer while the NO levels produced by neutrophils of CRC patients decreased significantly (p < 0.01). The same trends held true for the platelets.CONCLUSIONS:In obese patients with CRC, superoxide-generating activity increases in cancer cells, AT, neutrophils and platelets. The obesity should be considered as the additional oncological risk representing the potent predictor for the events realized in obese patients such as oxidative stress, inflammation, insulin resistance and endothelial dysfunction.
AIM:To determine the content of low-spin form of cytochrome P450 in primary tumors and liver metastases of the patients with metastatic colorectal cancer (mCRC) and and assess its prognostic significance.MATERIALS AND METHODS:The levels of the oxidized and low-spin forms of cytochrome P450 in the tissues of patients with mCRC were studied by electron paramagnetic resonance. To detect CYP 1A2 and CYP 1B1 isoforms, Western blot analysis was used. The activity of metalloprotreinases was studied by gelatine zymography.RESULTS:In the liver metastases and tissues adjacent to metastasis, the levels of low-spin forms of cytochrome P450 are lower than in the samples of conventionally normal liver tissue. Western blot analysis revealed that low-spin form of cytochrome P450 in primary tumors and liver metastases detected by electron paramagnetic resonance is attributed largely to CYP 1B1 isoform. The content of low-spin form of cytochrome P450 inversely correlated with the the activity of gelatinases (matrix metalloproteinase-2 and -9). The survival of patients with high levels of the low-spin form of cytochrome P450 in tumor tissues was higher than that of patients with low levels of the enzyme (105 months vs 61 months).CONCLUSION:In the primary tumors and liver metastases of patients with mCRC, the content of the low-spin form of cytochrome P450 decreased, which correlated inversely with patient's survival.
Вступ.У жінок постменопаузального віку рівень циркулюючого естрогену у сироватці крові та тканині грудної залози знижений, але частота розвитку раку грудної залози (РГЗ) залишається високою, що вказує на наявність інших чинників, що зумовлюють його виникнення.До останніх можна віднести здатність естрогену та його метаболітів порушувати рівновагу в редокс-стані органів та крові шляхом посилення генерування супероксидних радикалів, які виявляють як сигнальні, так і пошкоджуючі ефекти.Накопичилися дані щодо того, що окиснювальний метаболізм естрогену з утвореннями катехол-естроген-3,4-хінонів має потенціал ініціювати РГЗ.Мета.Дослідити рівень церулоплазміну (ЦП), трансферину (ТФ), NO-гемоглобіну (NO-Hb), метгемоглобіну (MetHb), «вільного» заліза, супероксид-і NO-генеруючої активності нейтрофілів та матриксних металопротеїназ-2 і -9 у крові хворих на РГЗ ІІ-ІІІ стадії з різним гормонорецепторним статусом пухлин.Об'єкт і методи.Досліджено кров хворих на РГЗ у репродуктивному та постменопаузальному віці.Рівень ЦП, ТФ, «вільного» заліза, геміхромів, MetHb, NO-Hb та убісеміхінону досліджували методом електронного парамагнітного резонансу (ЕПР) у низькотемпературному режимі (77 К).Швидкість генерування супероксидних радикалів нейтрофілами визначали методом ЕПР при кімнатній температурі з використанням спінового уловлювача TEMPONE-H («Sigma»).NO-генеруючу активність нейтрофілів крові визначали методом ЕПР з використанням технології Spin Traps за температури 77 K (спіновий уловлювач -діетилдитіокарбамат).Рівень активних форм желатиназ у сироватці крові визначали методом зимографії у поліакриламідному гелі.Результати.У пацієнток репродуктивного та постменопаузального віку з естроген-рецептор (ER)(+)/прогестерон-рецептор (PR)(+) та ER(-)/PR(-)-статусом пухлин рівень ЦП перевищував значення, характерні для донорів, а рівень ТФ був достовірно нижчим.Вміст у крові NO-Hb був найвищим у хворих на РГЗ у постменопаузальному віці з ER(-)/PR(-)-статусом пухлин та прямо корелював з NO-генеруючою активністю нейтрофілів (r=0,56; р<0,05).Активність матриксної металопротеїнази-9 у сироватці крові хворих з ER(-)/PR(-)статусом пухлин у 3,3 раза достовірно перевищувала таку у хворих з ER(+)/PR(+).У крові 78% хворих на РГЗ постменопаузального віку з ER(-)/PR(-) виявлено підвищення вмісту метаболітів естрогенів -хінонів та убісеміхінонів, рівень останніх прямо корелював зі стадією пухлинного процесу (r=0,58; р<0,05).Встановлено, що нейтрофіли в крові хворих репродуктивного віку з ER(+)/PR(+) та ER(-)/PR(-) генерують супероксидні радикали зі швидкістю, яка є відповідно у 9 та 18 разів вищою порівняно з донорами, а NO -більше ніж у 12 разів незалежно від гормонорецепторного статусу пухлин.Висновок.Виявлено порушення редокс-стану крові у хворих на РГЗ, зміни якого залежать від гормонорецепторного статусу пухлин, зокрема ER(+)/PR(+) та ER(-)/PR(-).Характерний для хворих на РГЗ редокс-стан крові формується підвищенням супероксид-та NO-генеруючої активності нейтрофілів, появою значних рівнів NO-Hb, MetHb, геміхромів, убісеміхінонів і активності
Актуальність.За останні десять років наше розуміння механізмів впливу жирової тканини (ЖТ) на пухлинне прогресування значно розширилося, однак до цього часу не розкрито механізми взаємодії адипоцитів із клітинами раку прямої кишки (РПК) за умов проведення променевої та хіміопроменевої терапії.Об'єкт і методи.Проведено проспективне рандомізоване одноцентрове дослідження.У дослідженні брали участь 110 хворих на місцево-поширений рак прямої кишки (мпРПК; ymrT3-4aN0-2M0-1, CRM-positive) з надмірною масою тіла в період з січня 2016 р. до грудня 2018 р.Пацієнтів рандомізували у співвідношенні 1:1 на основну групу (група А; n=57; променева терапія сумарною вогнищевою дозою 50,4 Гр (1,8 Гр х 28) та поліхіміотерапія на основі оксаліплатину) та групу порівняння (група Б; n=53; променева терапія сумарною вогнищевою дозою 50,4 Гр (1,8 Гр х 28) та монохіміотерапія на основі фторпіримідинів).Результати та їх обговорення.Зареєстровані рівні швидкості генерування супероксидних радикалів у ЖТ, яка контактувала з пухлиною, становили 0,58±0,15 (група А) та 0,70±0,12 нмоль/г тканини•хв (група Б) (р<0,001).У крові цих хворих виявлено зростання рівня вільних жирних кислот: у групі А до значень 2,05±0,15 ммоль/л, а в групі Б цей показник становив 2,48±0,20 ммоль/л при нормі 0,57±0,11 ммоль/л.Рівні 8--оксогуаніну в прилеглій до пухлини ЖТ хворих досліджуваних груп не мали статистично значущої відмінності -0,80±0,08 та 0,84±0,13 відповідно для груп А та Б (р=0,052).Висновки.Прилегла до пухлини ЖТ являє собою енергетичне депо, здатне виступати в ролі промотора пухлинного прогресування, забезпечуючи пухлину
It has been shown that the intensity of linearly polarized light transmitted through CdS single crystal depends on its temperature. It has been found that the temperature of crystal does not affect the linearity of light polarization at the exit of crystal, but leads only to rotation of the polarization plane. It has been ascertained that in the range between 11 to 170 °C, the temperature dependence of the linear expansion coefficient and the difference between the refractive indices of unusual and ordinary beams can be neglected.
BACKGROUND:Interaction between tumor cells and tumor microenvironment is critical for homeostasis of normal cells and tumor growth. Tumor cell - stroma interaction represents the potent factor able to initiate cancer and affect tumor progression and disease outcome. The tumors vary by their origin and microenvironment (proportion of stromal cells, their composition and activation state). The surgical stress and tumor microenvironment may potentiate acute hepatic failure in the patients with metastatic colorectal cancer (mCRC). Pathological effect of ischemia-reperfusion (I/R) consists in the increased generation of superoxide radicals (SR) and nitrogen oxide (NO) affecting the postresectional regeneration of liver tissue. Redox state of hepatic tissue in I/R setting upon resection of metastases may trigger the aggressiveness of residual cancer cells and regeneration or degradation of hepatic tissue. The aim of the study was to analyze redox state of hepatic tissue following surgery with Pringle maneuver (PM) in the patients with mCRC.MATERIALS AND METHODS:mCRC samples from 145 patients treated at National Cancer Institute, Ministry of Health of Ukraine, were analyzed. The patients obtained chemotherapy according to the approved international and national standards as well as clinical protocols. Two groups of patients were delineated according to the duration of the interruption of blood inflow due to PM, namely ≤ 45 min and > 45 min. The activity of FeS proteins in the electron transport chain (ETC) in mitochondria and lactoferrin (LF) level in the tissues were assessed by EPR (77К). The rates of SR and NO generation were determined with spin traps. The activity of matrix metalloproteinase (MMP)-2 and -9 was measured by gelatin zymography using SDS-polyacrylamide gel electrophoresis.RESULTS:In tissue of liver resected in the setting of > 45 min ischemia, ETC function in mitochondria was impaired (decreased activity of FeS protein of N-2 ETC complex I due to interaction with NO). This results in the hypoxia state and glycolysis with uncontrolled SR generation. In addition, the efficiency of detoxification system in hepatocytes is reduced substantially with increase in semiquinone and LF levels as well as MMP-2 and -9 activity as compared with liver without metastatic lesions that was not affected by I/R.CONCLUSIONS:The ischemic injury of liver in the setting of metastasis resection results from cell response to interruption of blood flow followed by reperfusion. The key factor in the genesis of reperfusion damage is uncontrolled increase of the levels of SR and their metabolites - reactive oxygen species as well as the increased MMP activity. Also, liver tissue affected by I/R contains high levels of xanthine oxidase metabolizing hypoxanthine and monoamine oxidase deaminizing biogenic amines. Both processes are the sources of SR.
мамографію, інші види сканування та біопсію (тест, при якому проводиться забір зразків тканин для перевірки на рак). Можливо, проводилися інші аналізи ракових клітин на наявність певних білків та генних змін. Можливо, ви пройшли інші сканування або процедури, щоб з'ясувати, чи не поширився рак. Ці тести допомагають лікарю встановити який у вас тип раку молочної залози, його стадію та лікування, яке може вам допомогти.
Un-doped and Ca-doped Eu x VO 4 and La l-x Eu x VO 4 vanadate nanoparticles were synthesized by sol-gel method. Phase compositions, morphology and luminescent characteristics of the samples were investigated. The Ca-doping influences on structure of luminescence spectra and chromaticity characteristics of all the samples even at low concentrations. The structure of Ca-related light absorption and emission centers is discussed using results about crystal structure and morphology of the samples.
In women of postmenopausal age, the level of circulating estrogen in blood serum and breast tissue is reduced, but the incidence of breast cancer in this female cohort remains high, indicating that there are other factors that contribute to the increase in morbidity. Aim: To investigate the level of Ceruloplasmin [CP], Transferrin [TF], NO-Hemoglobin [NO-Hb], Methemoglobin [MetHb], superoxide and NO-generating activity of neutrophils and Matrix Metalloproteinases-2 And -9 [MMP-2 and -9] in the blood of patients with breast cancer in relation with the hormone receptor status of tumors. Object and Methods:We have studied the blood samples of patients of reproductive and postmenopausal age with breast cancer of stages II-IIІ.The levels of CP, TF, "free" iron, hemichromes, MetHb, NO-Hb, ubisemiquinone, superoxide and NOgenerating activity of neutrophils were investigated by the method of Electron Paramagnetic Resonance [EPR].The level of active forms of gelatinases in blood serum was determined by zymography in a polyacrylamide gel. Results:In patients of reproductive and postmenopausal age with BC of ER+/PR+ and ER-/PR-status, the level of CP exceeded the corresponding index in healthy donors, and the level of TF was significantly lower than in control group.An increase in NO-Hb content in blood was observed, this index was the highest in patients of post-menopausal age with ER-/PR-status and directly correlated with NO-generating activity of neutrophils [r = 0.56; p <0.05].The activity of MMP-9 in the serum of patients with ER-/PR-status was significantly higher [by 3.3 times] than in patients with ER+/PR+ status.In the blood of 78% of postmenopausal patients with breast cancer of ER-/PR-status, an increased content of estrogen metabolites -quinones and ubisemiquinones was found, the latter level was directly correlated with the stage of the tumor process (r = 0.58; p <0.05).It has been established that neutrophils in the blood of patients of reproductive age with ER+/PR+ and ER-/PR-breast cancer generate SOR with a rate 9 and 18 times higher than in donors, respectively, and NO generation rate was more than 12 times higher in both subgroups. Conclusion:We have detected the disturbed redox state of blood with the accumulation of compounds with hormonal and progenotoxic effects in patients with breast cancer, and such alterations depend on the hormone receptor status of tumors.
Usually the stretching vibration of the A-H group in hydrogen-bonded complexes gives an intense, broad absorption in the IR spectrum. However in a few complexes it has proved difficult to detect this absorption in low temperature matrices. In this work the Ratajczak-Yaremko vibrational model of the hydrogen bond has been applied to simulate the IR spectrum obtained for one such complex: the pentachlorophenol-trimethylamine, PCP-TMA, hydrogen bonded complex isolated in an argon matrix. Quantum chemical calculations have also been carried out to gain further insight into this complex.