Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment
Aim: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethy...
Збережено в:
| Дата: | 2006 |
|---|---|
| Автори: | , , , , |
| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2006
|
| Назва видання: | Experimental Oncology |
| Теми: | |
| Онлайн доступ: | http://dspace.nbuv.gov.ua/handle/123456789/137933 |
| Теги: |
Додати тег
Немає тегів, Будьте першим, хто поставить тег для цього запису!
|
| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment / T.A. Khalikova, T.A. Korolenko, S.Ya. Zhanaeva, V.I. Kaledin, G. Kogan // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 308-313. — Бібліогр.: 34 назв. — англ. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
irk-123456789-137933 |
|---|---|
| record_format |
dspace |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Khalikova, T.A. Korolenko, T.A. Zhanaeva, S.Ya. Kaledin, V.I. Kogan, G. Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment Experimental Oncology |
| description |
Aim: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1→3)-β-D-glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues. Materials and Methods: The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases — cathepsins B and L — was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope. Results: It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris. Conclusion: Utilization of this polysaccharide BRM, sulfoethylated (1→3)-β-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects. |
| format |
Article |
| author |
Khalikova, T.A. Korolenko, T.A. Zhanaeva, S.Ya. Kaledin, V.I. Kogan, G. |
| author_facet |
Khalikova, T.A. Korolenko, T.A. Zhanaeva, S.Ya. Kaledin, V.I. Kogan, G. |
| author_sort |
Khalikova, T.A. |
| title |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment |
| title_short |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment |
| title_full |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment |
| title_fullStr |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment |
| title_full_unstemmed |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment |
| title_sort |
enhancing effect of new biological response modifier sulfoethylated (1→3)-β-d-glucan on antitumor activity of cyclophosphamide in the treatment |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2006 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137933 |
| citation_txt |
Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment / T.A. Khalikova, T.A. Korolenko, S.Ya. Zhanaeva, V.I. Kaledin, G. Kogan // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 308-313. — Бібліогр.: 34 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT khalikovata enhancingeffectofnewbiologicalresponsemodifiersulfoethylated13bdglucanonantitumoractivityofcyclophosphamideinthetreatment AT korolenkota enhancingeffectofnewbiologicalresponsemodifiersulfoethylated13bdglucanonantitumoractivityofcyclophosphamideinthetreatment AT zhanaevasya enhancingeffectofnewbiologicalresponsemodifiersulfoethylated13bdglucanonantitumoractivityofcyclophosphamideinthetreatment AT kaledinvi enhancingeffectofnewbiologicalresponsemodifiersulfoethylated13bdglucanonantitumoractivityofcyclophosphamideinthetreatment AT kogang enhancingeffectofnewbiologicalresponsemodifiersulfoethylated13bdglucanonantitumoractivityofcyclophosphamideinthetreatment |
| first_indexed |
2023-10-18T21:15:04Z |
| last_indexed |
2023-10-18T21:15:04Z |
| _version_ |
1796152315290320896 |
| spelling |
irk-123456789-1379332018-06-18T03:06:46Z Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment Khalikova, T.A. Korolenko, T.A. Zhanaeva, S.Ya. Kaledin, V.I. Kogan, G. Original contributions Aim: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1→3)-β-D-glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues. Materials and Methods: The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases — cathepsins B and L — was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope. Results: It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris. Conclusion: Utilization of this polysaccharide BRM, sulfoethylated (1→3)-β-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects. Цель: одним из перспективных методов противоопухолевой терапии является использование так называемых модификаторов биологического ответа, применяемых для активации эндогенных противоопухолевых механизмов и комбинируемых с классическими цитотоксическими препаратами. Цель данной работы — исследование эффекта сульфоэтилированного (1→ 3)-β-D-гликана (SEG) при лечении экспериментальных лейкозов мышей в комбинации с циклофосфаном (СРА) и его способность модулировать активность лизосомных ферментов в опухолевой ткани. Материалы и методы: солидные формы перевиваемых лейкозов мышей Р388 и L1210/1 трансплантировали мышам-самцам DBA/2. Для лечения использовали СРА (Биохимик, Саранск, Россия) и его комбинацию с SEG (Институт химии Словацкой Академии Наук, Братислава, Словакия). СРА вводили внутрибрюшинно на 10 сут после перевивки опухолей; SEG вводили внутрибрюшинно начиная с 3 сут после трансплантации лейкозов с интервалом в 3 дня. Терапевтический эффект оценивали путем измерения объема солидной опухоли. Активность цистеиновых протеаз — катепсинов В и L — определяли флюориметрическим методом, используя флюоресцентные субстраты Z-Arg-Arg-MCA и Z-Phe-Arg-MCA (Sigma, США). Апоптоз оценивали по результатам подсчета клеток с фрагментированными ядрами в световом микроскопе. Результаты: в работе показано, что использование SEG приводит к торможению опухолевого роста и потенцирует терапевтический эффект СРА, особенно при повторном введении в течение всего лечения. В сочетании с SEG терапевтический эффект половинной дозы СРА равнозначен или превышает действие полной дозы цитостатика. Воздействие СРА и SEG на использованные в исследовании опухоли реализуется в основном через индукцию апоптоза и сопровождается существенным повышением активности цистеиновых протеаз катепсинов В и L в опухолевой ткани. Наиболее высокая активность катепсинов В и L сопровождается максимальным подавлением опухолевого роста. Предположительно это обусловлено инфильтрацией опухолевой ткани макрофагами с высоким содержанием вышеназванных ферментов, где они фагоцитируют клетки в апоптозе. Выводы: использование сульфоэтилированного (1→3)-β-D-гликана, нового модификатора биологического ответа дает возможность существенно повысить эффективность противоопухолевой терапии стандартными цитостатиками без повышения их дозы, что позволяет избежать побочных эффектов данных препаратов. 2006 Article Enhancing effect of new biological response modifier sulfoethylated (1→3)-β-D-glucan on antitumor activity of cyclophosphamide in the treatment / T.A. Khalikova, T.A. Korolenko, S.Ya. Zhanaeva, V.I. Kaledin, G. Kogan // Experimental Oncology. — 2006. — Т. 28, № 4. — С. 308-313. — Бібліогр.: 34 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137933 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |