vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2023-20-3-243-255vestim-928Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEВлияние ионизирующего излучения (лучевой терапии) на структурно-функциональное состояние сывороточного альбумина у больных раком шейки маткиEffect of ionizing radiation (radiation therapy) on the structural and functional state of serum albumin with cervical cancerhttps://orcid.org/0000-0002-1518-7715ПузанН. Д.PuzanN. D.

Пузан Наталья Дмитриевна – научный сотрудник.

ул. Федюнинского, 4, 246007, Гомель

Natallia D. Puzan – Researcher, Institute of Radiobiology of the National Academy of Sciences of Belarus.

4, Fedyuninskу Str., 246007, Gomel

natali_lu@tut.byБеляковскийВ. Н.BelyakovskiyV. N.

Беляковский Василий Николаевич – доктор медицинских наук, профессор.

ул. Ланге, 5, 246000, Гомель

Vasiliy N. Belyakovskiy – D. Sc. (Med.), Professor, Gomel State Medical University.

5, Lange Str., 246000, Gomel

vnbel55@mail.ruЧешикИ. А.CheshikI. A.

Чешик Игорь Анатольевич – кандидат медицинских наук, доцент, директор.

ул. Федюнинского, 4, 246007, Гомель

Igor A. Cheshik – Ph. D. (Med.), Associate Professor, Director, Institute of Radiobiology of the National Academy of Sciences of Belarus.

4, Fedyuninskу Str., 246007, Gomel

igor.cheshik@gmail.comМихайловИ. В.MihailovI. V.

Михайлов Игорь Викторович – кандидат медицинских наук, доцент, заведующий кафедрой.

ул. Ланге, 5, 246000, Гомель

Igor V. Mihailov – Ph. D. (Med.), Associate Professor, Head of the Department, Gomel State Medical University.

5, Lange Str., 246000, Gomel

igor-mikhailov-2014@yandex.ruИнститут радиобиологии НАН БеларусиInstitute of Radiobiology of the National Academy of Sciences of BelarusГомельский государственный медицинский университетGomel State Medical University202302092023203243255Copyright © Пузан Н.Д., Беляковский В.Н., Чешик И.А., Михайлов И.В., 20232023Пузан Н.Д., Беляковский В.Н., Чешик И.А., Михайлов И.В.Puzan N.D., Belyakovskiy V.N., Cheshik I.A., Mihailov I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/928

Флуоресцентным методом исследования установлено, что общая концентрация альбумина находится в пределах нормальных значений как для здоровых, так и для онкобольных на протяжении всего курса лучевой терапии. Анализ показателей, характеризующих структурно-функциональное состояние сывороточного альбумина (эффективная концентрация альбумина, резерв связывания альбумина и индекс токсичности) у больных раком шейки матки, показал, что количество полноценно функционирующего белка статистически достоверно снижается при сравнении с таковым в группе здоровых людей.

При изучении влияния лучевой терапии на структурно-функциональное состояние сывороточного альбумина онкобольных определено следующее: в 57 % случаев значения показателя индекса токсичности, характеризующего заполнение альбуминовых центров токсичными лигандами, увеличиваются после курса лучевой терапии, а в 43 % − уменьшаются; после 1-го сеанса лучевой терапии определяется дальнейшая динамика показателя индекса токсичности после лечения; возможно, место проживания пациента является определяющим фактором при развитии индивидуальной реакции транспортной системы сывороточного альбумина на действие терапевтических доз ионизирующего излучения.

Определение альбуминовых показателей, характеризующих структурно-функциональное состояние сывороточного альбумина, в частности индекса токсичности, у больных раком шейки матки, следует использовать в качестве индивидуального диагностического и прогностического критерия в динамике наблюдения за пациентами, проходящими лучевую терапию.

The study of the literature on the detoxification properties of an albumin molecule and a prognostic value of determining albumin indicators allows us to conclude that it is undoubtedly important to assess the structural and functional properties of albumin in cancer patients at all stages of the diagnostic and treatment process already at the present time. At the same time, the lack of information makes it necessary and promising to widely introduce the fluorescent method for assessing total and effective albumin concentrations in the clinical and scientific work of oncologists.

Therefore, the aim of our work was to study the effect of radiation therapy on the structural and functional state of serum albumin in patients with cervical cancer.

In order to study radiation-induced changes in serum albumin when irradiated with therapeutic doses of ionizing radiation, the biological material (blood) of 28 people from the Gomel region was used: 1st group (control) – 13 healthy people; 2nd group – 15 patients diagnosed with cervical cancer who underwent remote gamma therapy (30 Gy). The collection of biological material in the 2nd group was carried out as follows: upon admission to patient treatment; after the 1st session of radiotherapy (2 Gy); after the 3rd session of radiotherapy (6 Gy); after the 5th session of radiotherapy (10 Gy); after the 7th session of radiotherapy (14 Gy); after the 10th session of radiotherapy (20 Gy), and after the 15th session of radiotherapy (30 Gy).

According to A. Gryzunov, G. E. Dobretsov’s method, the following indicators were determined: total albumin concentration (TAC) − the number of albumin molecules capable of binding toxic ligands is equal to the albumin concentration determined in any other way; effective albumin concentration (EAC) − the number of albumin binding centers is unoccupied by toxic ligands; the reserve of albumin binding (RAB) − it reflects the degree of structural modification of the protein; the index of toxicity (IT) − it characterizes the filling of albumin centers with toxic ligands.

The total albumin concentration is within normal values, both for healthy and cancer patients throughout the course of radiation therapy. The analysis of the indicators characterizing the structural and functional state of serum albumin (EAC, RAB, and IT) in patients with cervical cancer showed that the amount of fully functioning protein statistically significantly decreases when compared with a group of healthy people.

When studying the effect of radiation therapy on the structural and functional state of serum albumin in cancer patients, the following was determined: in 57 % of cases, the values of the IT indicator increase after a course of radiotherapy, and in 43 % − decrease;

after the 1st session of radiotherapy, further dynamics of IT after treatment is determined: if after 2 Gy the values of the IT indicator increase, then by the end of therapy this indicator will be higher than that when entering treatment, and, conversely, if after 2 Gy the values of the IT indicator decrease, then after the course of radiotherapy this indicator will be less than that when entering treatment;

it is possible that the patient’s place of residence is a determining factor in the development of an individual reaction of the serum albumin transport system to the effect of therapeutic doses of ionizing radiation.

The determination of albumin indicators characterizing the structural and functional state of serum albumin, in particular, the index of toxicity in patients with cervical cancer should be used as an individual diagnostic and prognostic criterion in the dynamics of observation of patients undergoing radiation therapy.

общая концентрация альбуминаэффективная концентрация альбуминарезерв связывания альбуминаиндекс токсичностилучевая терапиярак шейки маткиtotal albumin concentrationeffective albumin concentrationreserve of albumin bindingindex of toxicityradiation therapycervical cancerReferencesCervical cancer patient-derived orthotopic xenograft (PDOX) is sensitive to cisplatinum and resistant to nab-paclitaxel / T. Murakami [et al.]. // Anticancer Res. – 2017. – Vol. 37, N 1. – P. 61–65. https://doi.org/10.21873/anticanres.11289Murakami T., Murata T., Kawaguchi K., Kiyuna T., Igarashi K., Hwang H. K. [et al.]. Cervical cancer patient-derived orthotopic xenograft (PDOX) is sensitive to cisplatinum and resistant to nab-paclitaxel. Anticancer Research, 2017, vol. 37, no. 1, pp. 61–65. https://doi.org/10.21873/anticanres.11289Nomogram predicting overall survival in operable cervical cancer patients / R.-R. Zheng [et al.] // Int. J. Gynecol. Cancer. – 2017. – Vol. 27, N 5. – P. 987–993. https://doi.org/10.1097/IGC.0000000000000987Zheng R.-R., Huang X.-W., Liu W.-Y., Lin R.-R., Zheng F.-Y., Lin F. Nomogram predicting overall survival in operable cervical cancer patients. International Journal of Gynecological Cancer, 2017, vol. 27, no. 5, pp. 987–993. https://doi.org/10.1097/IGC.0000000000000987Tumor-targeting Salmonella typhimurium A1-R overcomes nab-paclitaxel resistance in a cervical cancer PDOX mouse model / K. Miyake [et al.]. // Arch. Gynecol. Obstet. – 2019. – Vol. 229, N 6. – P. 1683–1690. https://doi.org/10.1007/s00404-019-05147-3Miyake K., Murata T., Murakami T., Zhao M., Kiyuna T., Kawaguchi K. [et al.]. Tumor-targeting Salmonella typhimurium A1-R overcomes nab-paclitaxel resistance in a cervical cancer PDOX mouse model. Archives of Gynecology and Obstetrics, 2019, vol. 229, no. 6, pp. 1683–1690. https://doi.org/10.1007/s00404-019-05147-3Inhibiting the PI3K/AKT/mTOR signalling pathway with copper oxide nanoparticles from Houttuynia cordata plant: attenuating the proliferation of cervical cancer cells / H. Chen [et al.] // Artific. Cells, Nanomed. Biotechnol. – 2021. – Vol. 49, N 1. – P. 240–249. https://doi.org/10.1080/21691401.2021.1890101Chen H., Feng X., Gao L., Mickymaray S., Paramasivam A., Alfaiz F. A., Almasmoum H. A., Ghaith M. M., Almaimani R. A., Ibrahim I. A. A. Inhibiting the PI3K/AKT/mTOR signalling pathway with copper oxide nanoparticles from Houttuynia cordata plant: attenuating the proliferation of cervical cancer cells. Artificial Cells, Nanomedicine, and Biotechnology, 2021, vol. 49, no. 1, pp. 240–249. https://doi.org/10.1080/21691401.2021.1890101Prognostic value of systemic hemato-immunological indices in uterine cervical cancer: a systemic review, meta-analysis, and meta-regression of observational studies / X. Han [et al.] // Gynecol. Oncol. – 2021. – Vol. 160, N 1. – P. 351–360. https://doi.org/10.1016/j.ygyno.2020.10.011Han X., Liu S., Yang G., Hosseinifard H., Imani S., Yang L., Maghsoudloo M., Fu S., Wen Q., Liu Q. Prognostic value of systemic hemato-immunological indices in uterine cervical cancer: a systemic review, meta-analysis, and meta-regression of observational studies. Gynecologic Oncology, 2021, vol. 160, no. 1, pp. 351–360. https://doi.org/10.1016/j.ygyno.2020.10.011Modified Glasgow prognostic score is an independent prognostic factor in patients with cervical cancer undergoing chemoradiotherapy / Y. Xiao [et al.] // Int. J. Clin. Exp. Pathol. – 2015. – Vol. 8, N 5. – P. 5273–5281.Xiao Y., Ren Y.-K., Cheng H.-J., Wang L., Luo S.-X. Modified Glasgow prognostic score is an independent prognostic factor in patients with cervical cancer undergoing chemoradiotherapy. International Journal of Clinical and Experimental Pathology, 2015, vol. 8, no. 5, pp. 5273–5281.Wang, J. Identification and validation of potential mRNA-microRNA-long-noncoding RNA (mRNA-miRNA-lncRNA) prognostic signature for cervical cancer / J. Wang, C. Zhang // Bioengineered. – 2021. – Vol. 12, N 1. – P. 898–913. https://doi.org/10.1080/21655979.2021.1890377Wang J., Zhang C. Identification and validation of potential mRNA-microRNA-long-noncoding RNA (mRNA-miR-NA-lncRNA) prognostic signature for cervical cancer. Bioengineered, 2021, vol. 12, no. 1, pp. 898–913. https://doi.org/10.1080/21655979.2021.1890377Ермакова, Н. А. Роль химиотерапии на различных этапах лечения рака шейки матки / Н. А. Ермакова // Практ. онкология. – 2002. – Т. 3, № 3. – С. 211–219.Ermakova N. А. The role of chemotherapy at various stages of cervical cancer treatment. Prakticheskaya onkologiya [Practical oncology], 2002, vol. 3, no. 3, pp. 211–219 (in Russian).Deterioration of nutritional status of patients with locally advanced cervical cancer during treatment with concomitant chemoradiotherapy / M. Sanchez [et al.] // J. Hum. Nutr. Diet. – 2019. – Vol. 32, N 4. – P. 480–491. https://doi.org/10.1111/jhn.12649Sánchez M., Castro-Eguiluz D., Luvián-Morales J., Jiménez-Lima R., Aguilar-Ponce J. L., Isla-Ortiz D., Cetina L. Deterioration of nutritional status of patients with locally advanced cervical cancer during treatment with concomitant chemoradiotherapy. Journal of Human Nutrition and Dietetics, 2019, vol. 32, no. 4, pp. 480–491. https://doi.org/10.1111/jhn.12649T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways / H. Liu [et al.] // Bioengineered. – 2021. – Vol. 12, N 1. – P. 565–577. https://doi.org/10.1080/21655979.2021.1880732Liu H., Song M., Sun X., Zhang X., Miao H., Wang Y. T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways. Bioengineered, 2021, vol. 12, no. 1, pp. 565–577. https://doi.org/10.1080/21655979.2021.1880732Uracil-5-yl O-sulfamate: an illusive radiosensitizer. Pitfalls in modeling the radiosensitizing derivatives of nucleobases / P. Spisz [et al.] // J. Phys. Chem. B. – 2020. – Vol. 124, N 27. – P. 5600–5613. https://doi.org/10.1021/acs.jpcb.0c03844Spisz P., Zdrowowicz M., Kozak W., Chomicz-Mańka L., Falkiewicz K., Makurat S. [et al.]. Uracil-5-yl O-sulfamate: an illusive radiosensitizer. Pitfalls in modeling the radiosensitizing derivatives of nucleobases. Journal of Physical Chemistry B, 2020, vol. 124, no. 27, pp. 5600–5613. https://doi.org/10.1021/acs.jpcb.0c03844Al-Musywel, H. A. Effect of gold nanoparticles on radiation doses in tumor treatment: a Monte Carlo study / H. A. Al-Musywel, A. Laref // J. Lasers Med. Sci. – 2017. – Vol. 32, N 9. – P. 2073–2080. https://doi.org/10.1007/s10103-017-2329-0Al-Musywel H. A., Laref A. Effect of gold nanoparticles on radiation doses in tumor treatment: a Monte Carlo study. Journal of Lasers in Medical Science, 2017, vol. 32, no. 9, pp. 2073–2080. https://doi.org/10.1007/s10103-017-2329-0Powathil, G. G. Towards predicting the response of a solid tumour to chemotherapy and radiotherapy treatments: clinical insights from a computational model / G. G. Powathil, D. J. A. Adamson, M. A. J. Chaplain // PLOS Comp. Biol. – 2013. – Vol. 9, N 7. – P. e1003120. https://doi.org/10.1371/journal.pcbi.1003120Powathil G. G., Adamson D. J. A., Chaplain M. A. J. Towards predicting the response of a solid tumour to chemotherapy and radiotherapy treatments: clinical insights from a computational model. PLOS Computational Biology, 2013, vol. 9, no. 7, p. e1003120. https://doi.org/10.1371/journal.pcbi.1003120Rational design of cancer-targeted BSA protein nanoparticles as radiosensitizer to overcome cancer radioresistance / Y. Huang [et al.] // ACS Appl. Mater. Interfaces. – 2014. – Vol. 6, N 21. – P. 19217–19228. https://doi.org/10.1021/am505246wHuang Y., Luo Y., Zheng W., Chen T. Rational design of cancer-targeted BSA protein nanoparticles as radiosensitizer to overcome cancer radioresistance. ACS Applied Materials and Interfaces, 2014, vol. 6, no. 21, pp. 19217–19228. https://doi.org/10.1021/am505246wАртемова, Н. А. Нетрадиционные режимы фракционирования дозы как модификатор лучевой терапии у больных раком легкого / Н. А. Артемова // Здравоохранение. – 2008. – № 1. – С. 24–29.Artemova N. А. Unconventional dose fractionation regimens as a modifier of radiation therapy in patients with lung cancer. Zdravookhranenie [Healthcare], 2008, no. 1, pp. 24–29 (in Russian).Chemical and biological basis for development of novel radioprotective drugs for cancer therapy / R. Checker [et al.] // Free Rad. Res. – 2021. – Vol. 55, N 5. – P. 595–625. https://doi.org/10.1080/10715762.2021.1876854Checker R., Patwardhan R. S., Jayakumar S., Maurya D. K., Bandekar M., Sharma D., Sandur S. K. Chemical and biological basis for development of novel radioprotective drugs for cancer therapy. Free Radical Research, 2021, vol. 55, no. 5, pp. 595–625. https://doi.org/10.1080/10715762.2021.1876854Patient radiation exposure: imaging during radiation oncology procedures: executive summary of NCRP Report No. 184 / M. T. Milano [et al.] // J. Am. Coll. Radiol. – 2020. – Vol. 17, N 9. – P. 1176–1182. https://doi.org/10.1016/j.jacr.2020.02.002Milano M. T., Mahesh M., Mettler F. A., Elee J., Vetter R. J. Patient radiation exposure: imaging during radiation oncology procedures: executive summary of NCRP Report No. 184. Journal of the American College of Radiology, 2020, vol. 17, no. 9, pp. 1176–1182. https://doi.org/10.1016/j.jacr.2020.02.002Альбумин сыворотки крови в клинической медицине : сб. ст. / под ред. Ю. А. Грызунова, Г. Е. Добрецова. – М. : Ириус, 1994. – 226 с.Gryzunov Yu. A., Dobretsov G. E. (eds.). Serum albumin in clinical medicine: a collection of articles. Moscow, Irius Publ., 1994. 226 p. (in Russian).The influence of oxidative stress on serum albumin structure as a carrier of selected diazaphenothiazine with potential anticancer activity / M. Maciazek-Jurzyk [et al.] // Pharmaceuticals. – 2021. – Vol. 14, N 3. – P. 285. https://doi.org/10.3390/ph14030285.Maciążek-Jurczyk M., Morak-Młodawska B., Jeleń M., Kopeć W., Szkudlarek A., Owczarzy A., Kulig K., Rogóż W., Pożycka J. The influence of oxidative stress on serum albumin structure as a carrier of selected diazaphenothiazine with potential anticancer activity. Pharmaceuticals, 2021, vol. 14, no. 3, p. 285. https://doi.org/10.3390/ph14030285Ischemia-modified albumin: could it be a new oxidative stress biomarker for colorectal carcinoma? / H. Y. Ellidag [et al.]. // Gut and Liver. – 2013. – Vol. 7, N 6. – P. 675–680. https://doi.org/10.5009/gnl.2013.7.6.675Ellidag H. Y., Bulbuller N., Eren E., Abusoglu S., Akgol E., Cetiner M., Yılmaz N. Ischemia-modified albumin: could it be a new oxidative stress biomarker for colorectal carcinoma? Gut and Liver, 2013, vol. 7, no. 6, pp. 675–680. https://doi.org/10.5009/gnl.2013.7.6.675Systemic inflammatory score predicts overall survival in patients with cervical cancer / M. Xu [et al.]. // J. Cancer. – 2021. – Vol. 12, N 12. – P. 3671–3677. https://doi.org/10.7150/jca.56170Xu M., Wu Q., Cai L., Sun X., Xie X., Sun P. Systemic inflammatory score predicts overall survival in patients with cervical cancer. Journal of Cancer, 2021, vol. 12, no. 12, pp. 3671–3677. https://doi.org/10.7150/jca.56170Афанасьева, А. Н. Клиническое значение определения альбуминовых показателей у онкологических больных / А. Н. Афанасьева, В. А. Евтушенко // Анестезиология и реаниматология. – 2004. – № 6. – С. 64–68.Afanas’eva A. N., Evtushenko V. A. Clinical value of determination of albumin values in cancer patients. Anesteziologiya i reanimatologiya [Anesthesiology and intensive care], 2004, no. 6, pp. 64–68 (in Russian).Нямаа, Д. Влияние среды на функциональные и структурные свойства сывороточных альбуминов. II. Влияние температуры на N-форму сывороточного альбумина человека / Д. Нямаа, О. Бат-Эрдэнэ, Э. А. Бурштейн // Молекуляр. биология. – 1984. – Т. 18, вып. 4. – С. 972–977.Nyamaa D., Bat-Erdene O., Burstein E. A. The influence of the medium on the functional and structural properties of serum albumins. II. The effect of temperature on the N-form of human serum albumin. Molekulyarnaya biologiya [Molecular biology], 1984, vol. 18, no. 4, pp. 972–977 (in Russian).Афанасьева, А. Н. Влияние интраоперационной лучевой терапии на альбуминовые показатели крови больных раком желудка / А. Н. Афанасьева, В. А. Евтушенко // Рос. онколог. журн. – 2006. – № 2. – С. 41–44.Afanas’eva A. N., Evtushenko V. A. The effect of intraoperative radiotherapy on albumin blood count in patients with gastric cancer. Rossiiskii onkologicheskii zhurnal [Russian journal of oncology], 2006, no. 2, pp. 41–44 (in Russian).Дозы облучения населения Гомельской области от основных источников радиационного воздействия, в том числе медицинской рентгенодиагностики / Н. Г. Власова [и др.]. // Проблемы здоровья и экологии. – 2006. – № 3 (9). – С. 7–18.Vlasova N. G., Kuznetsov B. K., Visenberg Yu. V., Leshcheva S. V., Eventova L. N., Matskevich S. A., Kalinin D. I. Doses in Gomel population due to main sources of radiation, including chernobyl and medicine radiology. Problemy zdorov’ya i ekologii = Health and environmental issues, 2006, no. 3 (9), pp. 7–18 (in Russian).Клиническое значение определения состояния центров связывания сывороточного альбумина при беременности / Н. Д. Луковская [и др.]. // Вес. Нац. акад. навук Беларусі. Сер. мед. навук. – 2008. – № 3. – С. 58–63.Lukovskaya N. D., Gromyko N. L., Baranovskaya E. I., Malenchenko A. F. Clinical significance of determining the state of serum albumin binding centers during pregnancy. Vestsi Natsyyanal’nai akademii navuk Belarusi. Serуya medуtsynskikh navuk = Proceedings of the National Academy of Sciences of Belarus. Medical series, 2008, no. 3, pp. 58–63 (in Russian).

The authors declare that there are no conflicts of interest present.