Comparative Activity of Chlonisol and Lomustinе in Mice with Intraorbital Transplant of Ehrlich Carcinoma
pdf (Русский)

Keywords

сhlonisol
lomustine
intraorbital transplantation of tumors
Ehrlich Carcinoma
antitumor activity

How to Cite

Alexandrov, V. A., Zmitrichenko, Y. G., Stukov, A. N., Haritonova, N. N., Belyaeva, O. A., Suslov , D. N., Nyuganen, A. O., Tochilnikov, G. V., Latipova, D. K., & Semiglazova, T. Y. (2024). Comparative Activity of Chlonisol and Lomustinе in Mice with Intraorbital Transplant of Ehrlich Carcinoma. Voprosy Onkologii, 70(2), 286–291. https://doi.org/10.37469/0507-3758-2024-70-2-286-291

Abstract

Aim. To model the orbital tumor by intraorbital transplantation of Ehrlich carcinoma (EC) in mice and to evaluate the activity of the domestic compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) in this model in comparison with its structural analogous drug lomustine.

Materials and methods. To model intraorbital tumors in 40 BALB/c mice, tumor cells of the standard EC strain (1 × 106 cells in 0.05 ml of sterile 0.9 % sodium chloride solution) were used, which were injected using a thin needle transconjunctivally into the cavity of the right orbit above its lower wall. When testing the method (on 10 mice), it was shown that the tumor grows rapidly, destroys the structures, and spreads beyond the orbit. Other mice were divided into three groups (10 animals each) with a single dose of lomustine (50 mg/kg, per os), chlonisol (20 mg/kg, i.p.) or vehicle (control). The antitumor activity of the drugs was assessed by the inhibition of the transplanted tumor growth and the survival rate of the animals.

Results. Both the drugs inhibited tumor growth: lomustine — by 59-72 %, and chlonisol — by 95-100 % compared with the control (р < 0,01-0,0001). The inhibitory activity of chlorinisol was statistically significantly higher than that of lomustine. Median lifespan was increased by 28 % (p = 0.006) with lomustine treatment compared to control, and 212 % (p < 0.0001) with chlorinisol treatment. Median lifespan was increased by 28 % (p = 0.006) with lomustine treatment, and 212 % (p < 0.0001) with chlorinisol treatment compared to control. When the efficacy of the drugs was compared, chlorinisol showed a 144 % higher rate of efficacy than lomustine (p = 0.0005). Half of the mice in the chlorinisol group lived more than 90 days without recurrence, which can be considered as cure.

Conclusion. In mice with EC transplanted into the orbit, the antitumor activity of the compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) was statistically significantly higher than that of its structural analogue, the drug lomustine.

https://doi.org/10.37469/0507-3758-2024-70-2-286-291
pdf (Русский)

References

Бровкина А.Ф. Внутриглазные опухоли. Гл. 11: 725-795. Опухоли и опухолеподобные заболевания орбиты. Гл. 12: 796-886. В кн. под ред. А.Ф. Бровкиной и Ю.С. Астахова. Руководство по клинической офтальмологии. Изд. М.: ООО «Медицинское информационное агентство», 2014: 960.

[Brovkina A.F. Intraocular tumors. Ch. 11: 725-795. Tumors and tumor-like diseases of the orbit. Ch. 12: 796-886. In Ed. by A.F. Brovkina and Yu.S. Astakhov. Guide to clinical ophthalmology.-ed. Moscow: Medical Information Agency. 2014: 960. (In Rus)].

Williams B.K. Jr, Di Nicola M. Ocular Oncology - Primary and metastatic malignancies. Med Clin North Am. 2021; 105(3): 531-50.-DOI: https://doi.org/10.1016/j.mcna.2021.02.005.

Tailor T.D., Gupta D., Dalley R.W., et al. Orbital neoplasms in adults: clinical, radiologic, and pathologic review. Radiographics. 2013; 33(6): 1739-58.-DOI: https://doi.org/10.1148/rg.336135502.

Гришина Е.Е. Метастатическое поражение органа зрения. Клиническая офтальмология. 2001; 2(1): 15-7.

[Grishina E.E. Metastatic damage to the organ of vision. Clinical ophthalmology. 2001; 2(1): 15-7. (In Rus)].

Wilson M.W., Czechonska G., Finger P.T., et al. Chemotherapy for eye cancer. Surv Ophthalmol. 2001; 45(5): 416–44.-DOI: 10.1016/s0039-6257(00)00210-1.

Стуков А.Н., Харитонова Н.Н., Куликов А.Н., и др. Активность отечественного противоопухолевого соединения хлонизол на моделях опухолей век (экспериментальное исследование). Вестник офтальмологии. 2022; 138(4): 6-14.

[Stukov A.N., Kharitonova N.N., Kulikov A.N., et al. Activity of domestic antitumor compound chlonizol on models of eyelid tumors (experimental study). Bulletin of Ophthalmology. 2022; 138(4): 6-14. (In Rus)].

Островская Л.А., Филов В.А., Ивин Б.А., и др. Хлонизол – новый эффективный противоопухолевый препарат из класса нитрозоалкилмочевин. Российский биотерапевтический журнал. 2004; 3(1): 37–48.

[Ostrovskaya L.A., Filov V.A., Ivin B.A., et al. Chlonisol – the new alkylnitrosourea drug with antitumor activity. Russian Biotherapeutic Journal. 2004; 3(1): 37-48. (in Rus)].

Stukov A.N., Esikov K.A., Usmanova L.M., et al. Synthesis and antitumor activity of 2-[3-(2-chloroethy)-3-nitrosoureido]-1,3-propanediol (chlonisol). Pharmaceutical Chemistry Journal. 2020; 54(6): 579-81.-DOI: https://doi.org/10.1007/s11094-020-02242-7.

Насхлеташвили Д.Р., Банов С.М., Бекяшев А.Х., и др. Практические рекомендации по лекарственному лечению метастатических опухолей головного мозга. В кн. Злокачественные опухоли: Практические рекомендации RUSSCO №3s2. 2020; 10.08.

[Naskhletashvili D.R., Banov S.M., Bekyashev A.Kh., et al. Practical guidelines for drug treatment of metastatic brain tumors. In book: Malignant Tumors: RUSSCO Practice Guidelines No. 3s2. 2020; 10.08. (In Rus)].

Weller M., Le Rhun E. How did lomustine become standard of care in recurrent glioblastoma? Cancer Treat Rev. 2020; 87: 102029.-DOI: https://doi.org/10.1016/j.ctrv.2020.102029.

Трещалина Е.М., Жукова О.С., Герасимова Г.К., и др. Глава 39. Методические рекомендации по доклиническому изучению противоопухолевой активности лекарственных средств. 640–654 сс. В кн. под ред. А.Н. Миронов и др. Руководство по проведению доклинических исследований лекарственных средств. Часть первая: в двух томах. Изд. Москва: Гриф и К. 2012; 1: 944.

[Treshchalina E.M., Zhukova O.S., Gerasimova G.K., et al. Chapter 39. Guidelines for the preclinical study of the antitumor activity of drugs. 640-654 p. In Ed. by A.N. Mironov, et al. Guidelines for conducting preclinical studies of drugs. Part one: in two volumes. Moscow: Grif and K. 2012; 1: 944. (In Rus)].

Островская Л.А, Корман Д.Б., Дементьева Н.П., и др. Препараты класса алкилнитрозомочевин в отечественной противоопухолевой химиотерапии. Российский биотерапевтический журнал. 2004; 3(1): 24-36.

[Ostrovskaya L.A., Korman D.B., Dementieva N.P., et al. Drugs of the alkylnitrosourea class in domestic antitumor chemotherapy. Russian Biotherapeutic Journal. 2004; 3(1): 24-36. (In Rus)].

Змитриченко Ю.Г., Стуков А.Н., Александров В.А., и др. Активность 2-[3-(2-хлорэтил)-3-нитрозоуреидо]-1,3-пропандиола (хлонизола) в сравнении с ломустином на модели интракраниально трансплантированных опухолей у мышей. Фармакокинетика и фармакодинамика. 2022; (3): 3-9.-DOI: https://doi.org/10.37489/2587-7836-2022-3-26-32.

[Zmitrichenko Yu.G., Stukov A.N., Aleksandrov V.А., et al. Activity of 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propandyоl (chlonisol) versus lomustine in intracranial transplanted tumor model in mice. Pharmacokinetics and Pharmacodynamics. 2022; (3): 26-32. -DOI: https://doi.org/10.37489/2587-7836-2022-3-26-32. (In Rus)].

Alexandrov V.A., Stukov A.N., Zmitrichenko Y.G., Tochilnikov G.V. Сomparative activity of chlonisol and temozolomide in mice after intracranial transplantation of Еhrlich carcinoma and HER2-positive breast cancer. Pharmaceutical Chemistry J. 2022; 56 (9): 1179-182.-DOI: https://doi.org/10.1007/s11094-022-02773-1.

Муразов Я.Г., Стуков А.Н., Змитриченко Ю.Г., Точильников Г.В. Влияние отечественного противоопухолевого соединения из класса нитрозоалкилмочевин хлонизола на общую выживаемость лабораторных грызунов с интракраниальными опухолями: метаанализ результатов доклинических исследований. Лабораторные животные для научных исследований. 2022; (2).-DOI: https://doi.org/10.29296/2618723X-2022-02-05.

[Murazov Ya.G., Stukov A.N., Zmitrichenko Iu.G., Tochilnikov G.V. The effect of the domestic antitumor compound chlonisol from the class of nitrosoalkylureas on the overall survival of laboratory rodents with intracranial tumors: a metaanalysis of preclinical studies. Laboratornye Zhivotnye dlya nauchnych issledovanii = Laboratory Animals for Science. 2022; (2).-DOI: https://doi.org/10.29296/2618723X-2022-02-05. (In Rus)].

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

© АННМО «Вопросы онкологии», Copyright (c) 2024