High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels

Aim: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. Methods: EPR at the room temperature and 77...

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Date:2006
Main Authors: Burlaka, A.P., Sidorik, E.P., Ganusevich, I.I., Lestchenko, Yu.M., Burlaka, A.А., Osinsky, S.P.
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Language:English
Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2006
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Cite this:High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels / A.P. Burlaka, E.P. Sidorik, I.I. Ganusevich, Yu.M. Lestchenko, A.A. Burlaka, S.P. Osinsky // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 323-325. — Бібліогр.: 13 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
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author Burlaka, A.P.
Sidorik, E.P.
Ganusevich, I.I.
Lestchenko, Yu.M.
Burlaka, A.А.
Osinsky, S.P.
author_facet Burlaka, A.P.
Sidorik, E.P.
Ganusevich, I.I.
Lestchenko, Yu.M.
Burlaka, A.А.
Osinsky, S.P.
citation_txt High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels / A.P. Burlaka, E.P. Sidorik, I.I. Ganusevich, Yu.M. Lestchenko, A.A. Burlaka, S.P. Osinsky // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 323-325. — Бібліогр.: 13 назв. — англ.
collection DSpace DC
description Aim: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. Methods: EPR at the room temperature and 77 °K, Spin Traps technology and zymography in polyacrylamide gels were applied. Results: In the vessels isolated from rectal tumors and Arteria rectalis superior high levels of ROS, NO· and formation of complexes of NO· with FeS-proteins at the sites of electron-transporting chain of mitochondria have been detected. High activities of MMP-2 and MMP-9 in vascular wall were also observed. The direct positive correlation between the rate of NO· generation and formation of complexes of NO·· with FeS-proteins as well as between ROS and NO formation and MMPs activities have been revealed. Conclusion: Altered oxidative equilibrium in mitochondria of cells in vascular wall promotes formation of cell hypoxia and its autocatalytic potentiation accompanied with activation of MMPs. Цель: изучить взаимоотношение между уровнями образования активных форм кислорода (АФК) и оксида азота (ОА) и активности матриксных металлопротеиназ (MMPs) MMP-2 и MMP-9 в сосудах, изолированных из опухолевой ткани прямой кишки, и в Arteria rectalis superior. Методы: ЭПР при комнатной температуре и при 77 °K, технология спиновых ловушек, зимофрафия в полиакриламидном геле. Результаты: в сосудах, изолированных из опухолевой ткани прямой кишки, и в Arteria rectalis superior обнаружены высокие уровни образования АФК, · и комплексов · с FeS-белками в участках цепи митохондрий. Определена также высокая активность MMP-2 и MMP-9 в стенке сосудов, находящихся в опухолевом узле. Обнаружена прямая положительная корреляция между величиной образования · и образованием комплексов · с белками, а также между образованием АФК и NO и активность MMPs. Выводы: измененное окислительное равновесие в митохондриях клеток стенки сосудов, находящихся в опухолевой ткани, усиливает формирование в них клеточной гипоксии, ее аутокаталитическое потенцирование, что сопровождается активацией в этих клетках MMPs
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fulltext Experimental Oncology ���� ��������� ����� ��ecem�er�� ������� ��������� ����� ��ecem�er�� ����ecem�er�� ����� ��� ��� It is known that ROS and NO may activate directly and/or via signaling molecules the expression of a num�er of genes controlling the function of the vessels �oth at normal and pathologic states [1]. The angiogenesis is tightly linked to the development of tumor and malignant progression�� in particular metastasis. It is clearly shown that tumor invasion as well as metastasis is accompanied with intra- and extravasation�� and destruction of extracellular matrix �y matrix metalloproteinases �MMPs���� in particular�� MMP-� and MMP-9 [��� �]. There is evidence that degradation and reorganization of the extracellular matrix are key events in vascular remodeling [4]. It was determined that �oth pro-MMP-� and pro�MMP-9 secreted from human vascular smooth muscle cells are activated �y ROS [�]. The activations of MMP-� and MMP-9 in human gastric cancer �y ROS as well as NO were o�served [��]. Taking into account the a�ove mentioned data this study was aimed to detect the levels of generation of ROS and NO and activities of MMP-� and MMP-9 in vessels isolated from rectal tumor and adjacent normal tissue. Twenty seven patients undergoing surgical resection of histologically proven rectal cancer �Т�N1М��� grade G��� were included into the trial. The patients were not treated previously. All patients underwent poten- tially curative resections. The vessels were o�tained �y means of preparation of freshly harvested tumor tissue with anatomical tools under magnification that allows to yield at least 1�� mg of vascular materials. In addi- tion�� a. rectalis superior feeding the tumor node in the rectum was o�tained �y the resection of superampullar part of rectum on the distance of 4�� cm from tumor �oundary. The weight of o�tained vascular specimen was approximately ��� mg. Moreover�� the �ranches of a. gastroepiploica sinistra �at least 1�� mg�� were o�tained �y the operation of patients with gastric ulcer �n = 7��. Local ethics committee approval was o�tained and all patients gave informed consent. O�tained vascular tissues were snap frozen in liquid nitrogen at the time of operation and stored at �7� °C. The superoxide radical-anions formation was assessed �y the method of EPR with the use of 1-hy- droxy-������������-tetramethyl-4-oxopiperidin �Russia�� and Spin Traps technology. The rates of superoxide radical-anions generation were calculated in nmol/g fresh tissue per min. The level of NO was determined using diethyldithiocar�omate spin trap �Sigma�� USA�� and EPR technology. The generation of NO was registered during � min followed �y cessation of NO generation �y liquid nitrogen �77 K��. The levels of NO were calculated in nmol/g fresh tissue. Activities of MMP-� and MMP-9 were determined �y zymography in 1�% polyacrylamide gel with the ad- dition of �.1% of gelatin as su�strate and using MMP-� and MMP-9 standards �Sigma�� USA�� [7]. The results were statistically evaluated �y computer programs Statistics ��.� and Exel ���� using paramet- ric and correlation analysis. In the vessels isolated from tumor tissue and in a. rectalis superior�� there have �een revealed elevated levels of generation rate of superoxide radical-anions compared to those in �ranches of a. gastroepiploica sinistra �Fig. 1��. Both in the vascular tissue isolated from tumors and a. rectalis superior�� activation of NO· synthesis �y NO-synthase systems�� in particu- lar�� mNOS has �een revealed. In the tumor vessels�� NO· levels were at the range of �.7� nmol/g of fresh tissue�� whilst in a. rectalis superior NO· level yielded �.�1 nmol/g of fresh tissue �Fig. ���. These indices are significantly higher than those in a. gastroepiploica sinistra �Fig. ���. It has to �e mentioned that significant HIGH FORMATION OF SUPEROXIDE ANION AND NITRIC OXIDE, AND MATRIX METALLOPROTEINASES ACTIVITY IN VASCULAR WALL OF RECTAL CARCINOMA VESSELS A.P. Burlaka1, E.P. Sidorik1, I.I. Ganusevich1, *, Yu.M. Lestchenko3, A.A. Burlaka2, S.P. Osinsky1 1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine 2O.O. Bogomolets National Medical University, MH of Ukraine, Kyiv, Ukraine 3L.P. Shupik Kyiv Medical Academy of Postgraduate Education, MH of Ukraine, Kyiv, Ukraine Aim: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. Methods: EPR at the room temperature and 77 °K, Spin Traps technology and zymography in polyacrylamide gels were applied. Results: In the vessels iso- lated from rectal tumors and Arteria rectalis superior high levels of ROS, NO· and formation of complexes of NO· with FeS-proteins at the sites of electron-transporting chain of mitochondria have been detected. High activities of MMP-2 and MMP-9 in vascular wall were also observed. The direct positive correlation between the rate of NO· generation and formation of complexes of NO·· with FeS-proteins as well as between ROS and NO formation and MMPs activities have been revealed. Conclusion: Altered oxidative equilibrium in mitochondria of cells in vascular wall promotes formation of cell hypoxia and its autocatalytic potentiation accompanied with activation of MMPs. Key Words: vascular wall, radical oxygen species, nitric oxide, matrix metalloproteinases-2 and -9. Received: November 21, 2006. *Correspondence: E-mail: osion@onconet.kiev.ua Abbreviations used: NO — nitric oxide; ROS - radical oxygen species. Exp Oncol ����� ���� 4�� ������� SHORT COMMUNICATIONS ��4 Experimental Oncology ���� ��������� ����� ��ecem�er�� differences �etween the rate of superoxide radical- anions generation and NO levels in vessels feeding the region of gastric wall with ulcer lesion and those in vessels feeding the tumor tissue were determined. The specificity of increased formation of reactive oxy- gen and nitrogen species in tumor vessels is required to �e confirmed in the special investigation with the extended spectra of vascular specimens. Fig. 1. The rate of superoxide radical-anions generation in the vessels isolated from tumors �1�� and A. rectalis superior �2�� compared with such in vessels isolated from stomach wall in patient with gastric ulcer �3�� Fig. 2. The levels of NO in the vessels isolated from tumors �1�� and Arteria rectalis superior �2�� compared with such in vessels isolated from stomach wall in patient with gastric ulcer �3�� Intensity of EPR signal in the region of the factor of spectroscopic splitting�� g = �.���� on the EPR spectra of the vessels isolated from tumors differentiated from such o�tained with a. rectalis superior �Fig. ���. Fig. 3. EPR spectra of vessels isolated from tumor of rectum �1���� and Arteria rectalis superior �2�� *g = �.�� characterizes the level of generated NO·-FeS-proteins complexes in mitochondrial mem�ranes. As we have reported earlier [�]�� the intensity of this signal responds to the level of NO-FeS-protein com- plexes generated upon interaction of NO· with FeS-pro- teins of respiratory chain of mitochondrial mem�ranes�� in particular with the proteins from N and S clusters in NA�PH-u�iquinone-oxidoreductase and succinatede hydrogenase�� respectively. In the tumoral vessels�� high content of NO-FeS-protein complexes �1.� ± �.11 a. u�� compared to such ��.�� ± �.�� a. u�� in a. rectalis su- perior�� was revealed �Fig. 4��. One should note that in normal state such complexes are generated at physi- ologic concentrations ��.1� ± �.�1 a. u�� for regulation of the rate of electron flow through respiratory chain of mitochondria. High levels of the complexes of NO with FeS-proteins in mitochondria are considered as indexes of oxidative reactivity of the cells further expressed �y NO effects in the formation of cell hypoxia and tumor progression. Mechanism of such distur�ance upon chemical carcinogens and during tumor growth was descri�ed in our earlier investigations [���� 9]. Fig. 4. �ependence �etween the level of generation of NO·- FeS-proteins complexes at the sites of respiratory chain of mitochondria of cellular elements of the tumoral vessels and concentration of NO· synthesized in the vascular wall of rectal tumor vessels Also�� we have revealed the direct positive relation �etween generation of NO· complexes with FeS-pro- teins at the sites of respiratory chain of mitochondria in the vessels of rectal tumors and concentration of NO· produced in the tumor �r = �.�4; p < �.�1��. In the vessels isolated from tumor tissues and in a. rectalis superior high levels of MMP-� and MMP-9 activities were o�served �Fig. ����� especially of the last one that is considered characteristic for vascular endothelium and play a pivotal role in the processes related to the formation and function of vessels �oth at normal and pathological states. It is known that physiologic state of the vessels is characterized �y very low �up to zero�� activities of MMP-� and MMP-9. Upon malignant progression activities of MMP-� and MMP-9 are increased making the conditions for intra- and extravasation of tumor cells �y the destruction of extracellular matrix that can results in the promotion of tumor invasion and metastasis [��� �]. In the vessels of tumor and a. rectalis superior the direct positive correlations �etween the levels of ROS and NO· generation and activities of MMP-� and MMP-9 have �een revealed �r = �.��; r = �.4�; r = �.47; r = �.���; p < �.���� respectively�� that characterizes the regulatory influence of ROS and NO· toward gelatina- ses via activation of latent forms of the enzymes [��]. Experimental Oncology ���� ��������� ����� ��ecem�er�� ������� ��������� ����� ��ecem�er�� ����ecem�er�� ����� ��� ��� Fig. 5. Activities of matrix metalloproteinases in the vessels isolated from tumor �1�� and in a. rectialis superior �2�� It is known that superoxide radical-anions produced �y endothelial and vascular smooth muscle cells may activate specific signal transduction pathways and coordinate interrelated pathologic reactions in the vascular wall [1�]. There are the data showing that the process of extravasation is potentiated simultaneously with an increase of NO· level generated �y human НТ1��� fi�rosarcoma cells [11]. In conclusion�� taking into account the a�ove men- tioned data and the results of other authors [��� 1���1�] it may �e supposed that high levels of ROS and NO generated in the vascular wall participate in the forma- tion of cellular hypoxia and activation of matrix metal- loproteinases in the cellular elements of tumor vessels. These events may contri�ute to the metastatic process simultaneously with those o�served in tumor cells. REFERENCES 1. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 2002; 3: 214–20. 2. Davidson B, Reich R, Risberg B, Nesland JM. The bio- logical role and regulation of matrix metalloproteinases (MMP) in cancer. Arch Pathol 2002; 3: 47–53. 3. Curran S, Murray GI. Matrix metalloproteinases: mo- lecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 2000; 36: 1621–30. 4. Rojas A, Figueroa H, Re L, Morales MA. Oxidative stress at the vascular wall. Mechanistic and pharmacological aspects. Arch Med Res 2006; 37: 436–48. 5. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage- derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 1996; 98: 2572–9. 6. Burlaka AP, Sidorik EP, Ganusevich II, Osinsky SP. Effects of radical oxygen species and NO: formation of intra- cellular hypoxia and activation of matrix metalloproteinases in tumor tissues. Exp Oncol 2006; 28: 49–53. 7. De Clerck YA, Perez N, Shimada H, Boone TC, Lanq- ley KE, Taylor SM. Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 1992; 52: 701–8. 8. Emmanuel NM, Kavetskiy RE, Tarusov BN, Sidorik EP. Biophysics of cancer. Kyiv: Naukova Dumka, 1976; 296 p (In Russian). 9. Burlaka AP, Sidorik EP. Radical oxygen species and nitric oxide upon tumorigenesis. Kyiv: Naukova Dumka, 2006; 228 p (In Ukrainian). 10. Touyz RM. Reactive oxygen species, vascular oxida- tive stress, and redox signaling in hypertension. Hypertension 2004; 44: 248. 11. Lala PK. Significance of nitric oxide in carcinogenesis, tumor progression and cancer therapy. Cancer Metastasis Rev 1998; 17: 1–6. 12. Ambs S, Merriam WG, Ogunfusika MO, Bennett WP, Ichibe N, Hussain SP, Tzeng EE, Geller DA, Billiar TR, Harris CC. p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. Nat Med 1998; 4: 1371–6. 13. Jenkins DC, Charles LG, Thomsen LL,Moss DW, Holmes LS, Baylis SA. Roles of nitric oxide in tumor growth. Proc Natl Acad Sci (USA) 1995; 92: 4392–6. Высокий уроВень образоВания супероксидного радикал-аниона и оксида азота и актиВности матриксных металлопротеиназ В стенке сосудоВ опухолей прямой кишки Цель: изучить взаимоотношение между уровнями образования активных форм кислорода (АФК) и оксида азота (ОА) и активности матриксных металлопротеиназ (MMPs) MMP-2 и MMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, иMMPs) MMP-2 и MMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, и) MMP-2 и MMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, иMMP-2 и MMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, и-2 и MMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, иMMP-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, и-9 в сосудах, изолированных из опухолево�� ткани прямо�� кишки, и в Arteria rectalis superior. Методы: ЭПР при комнатно�� температуре и при 77 °K, техноло�ия спиновых ловушек, зимо�рафия вK, техноло�ия спиновых ловушек, зимо�рафия в, техноло�ия спиновых ловушек, зимо�рафия в полиакриламидном �еле. Результаты: в сосудах, изолированных из опухолево�� ткани прямо�� кишки, и в Arteria rectalis superior обнаружены высокие уровни образования АФК, NONO· и комплексов NONO· с FeS-белками в участках �лектронтранспортно�� �епис FeS-белками в участках �лектронтранспортно�� �епиFeS-белками в участках �лектронтранспортно�� �епибелками в участках �лектронтранспортно�� �епи митохондри��. Определена также высокая активность MMP-2 и MMP-9 в стенке сосудов, находя�ихся в опухолевом узле.MMP-2 и MMP-9 в стенке сосудов, находя�ихся в опухолевом узле.-2 и MMP-9 в стенке сосудов, находя�ихся в опухолевом узле.MMP-9 в стенке сосудов, находя�ихся в опухолевом узле.-9 в стенке сосудов, находя�ихся в опухолевом узле. Обнаружена прямая положительная корреля�ия между величино�� образования NONO· и образованием комплексов NONO· с FeS-с FeS-FeS- белками, а также между образованием АФК и NO и активность�� MMPs.NO и активность�� MMPs. и активность�� MMPs.MMPs. Выводы: измененное окислительное равновесие в митохондриях клеток стенки сосудов, находя�ихся в опухолево�� ткани, усиливает формирование в них клеточно�� �ипоксии, ее аутокаталитическое потен�ирование, что сопровождается актива�ие�� в �тих клетках MMPs.MMPs.. Ключевые слова: сосудистая стенка, активные формы кислорода, оксид азота, матриксные металлопротеиназы-2 и -9. Copyright © Experimental Oncology, 2006
id nasplib_isofts_kiev_ua-123456789-137932
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
issn 1812-9269
language English
last_indexed 2025-12-07T16:03:16Z
publishDate 2006
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
record_format dspace
spelling Burlaka, A.P.
Sidorik, E.P.
Ganusevich, I.I.
Lestchenko, Yu.M.
Burlaka, A.А.
Osinsky, S.P.
2018-06-17T19:12:49Z
2018-06-17T19:12:49Z
2006
High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels / A.P. Burlaka, E.P. Sidorik, I.I. Ganusevich, Yu.M. Lestchenko, A.A. Burlaka, S.P. Osinsky // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 323-325. — Бібліогр.: 13 назв. — англ.
1812-9269
https://nasplib.isofts.kiev.ua/handle/123456789/137932
Aim: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. Methods: EPR at the room temperature and 77 °K, Spin Traps technology and zymography in polyacrylamide gels were applied. Results: In the vessels isolated from rectal tumors and Arteria rectalis superior high levels of ROS, NO· and formation of complexes of NO· with FeS-proteins at the sites of electron-transporting chain of mitochondria have been detected. High activities of MMP-2 and MMP-9 in vascular wall were also observed. The direct positive correlation between the rate of NO· generation and formation of complexes of NO·· with FeS-proteins as well as between ROS and NO formation and MMPs activities have been revealed. Conclusion: Altered oxidative equilibrium in mitochondria of cells in vascular wall promotes formation of cell hypoxia and its autocatalytic potentiation accompanied with activation of MMPs.
Цель: изучить взаимоотношение между уровнями образования активных форм кислорода (АФК) и оксида азота (ОА) и активности матриксных металлопротеиназ (MMPs) MMP-2 и MMP-9 в сосудах, изолированных из опухолевой ткани прямой кишки, и в Arteria rectalis superior. Методы: ЭПР при комнатной температуре и при 77 °K, технология спиновых ловушек, зимофрафия в полиакриламидном геле. Результаты: в сосудах, изолированных из опухолевой ткани прямой кишки, и в Arteria rectalis superior обнаружены высокие уровни образования АФК, · и комплексов · с FeS-белками в участках цепи митохондрий. Определена также высокая активность MMP-2 и MMP-9 в стенке сосудов, находящихся в опухолевом узле. Обнаружена прямая положительная корреляция между величиной образования · и образованием комплексов · с белками, а также между образованием АФК и NO и активность MMPs. Выводы: измененное окислительное равновесие в митохондриях клеток стенки сосудов, находящихся в опухолевой ткани, усиливает формирование в них клеточной гипоксии, ее аутокаталитическое потенцирование, что сопровождается активацией в этих клетках MMPs
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
Experimental Oncology
Short communications
High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
высокий уровень образования супероксидного радикал-аниона и оксида азота и активности матриксных металлопротеиназ в стенке сосудов опухолей прямой кишки
Article
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spellingShingle High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
Burlaka, A.P.
Sidorik, E.P.
Ganusevich, I.I.
Lestchenko, Yu.M.
Burlaka, A.А.
Osinsky, S.P.
Short communications
title High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
title_alt высокий уровень образования супероксидного радикал-аниона и оксида азота и активности матриксных металлопротеиназ в стенке сосудов опухолей прямой кишки
title_full High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
title_fullStr High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
title_full_unstemmed High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
title_short High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
title_sort high formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels
topic Short communications
topic_facet Short communications
url https://nasplib.isofts.kiev.ua/handle/123456789/137932
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AT ganusevichii highformationofsuperoxideanionandnitricoxideandmatrixmetalloproteinasesactivityinvascularwallofrectalcarcinomavessels
AT lestchenkoyum highformationofsuperoxideanionandnitricoxideandmatrixmetalloproteinasesactivityinvascularwallofrectalcarcinomavessels
AT burlakaaa highformationofsuperoxideanionandnitricoxideandmatrixmetalloproteinasesactivityinvascularwallofrectalcarcinomavessels
AT osinskysp highformationofsuperoxideanionandnitricoxideandmatrixmetalloproteinasesactivityinvascularwallofrectalcarcinomavessels
AT burlakaap vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški
AT sidorikep vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški
AT ganusevichii vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški
AT lestchenkoyum vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški
AT burlakaaa vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški
AT osinskysp vysokiiurovenʹobrazovaniâsuperoksidnogoradikalanionaioksidaazotaiaktivnostimatriksnyhmetalloproteinazvstenkesosudovopuholeiprâmoikiški