Kidney Injury in Cancer Therapy

Бурнашева, Е. В.; Shatokhin, Y. V.; Снежко, И. В.; Мацуга, А. А.

doi:10.24884/1561-6274-2018-22-5-17-24

Cited by 7 publications

(1 citation statement)

References 17 publications

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“…Наряду с относительно низкой эффективностью цитотоксических препаратов, обусловленной их невысокой избирательностью, убедительно показаны такие множественные побочные эффекты, как миелосупрессия, снижение фертильности, развитие вторичных злокачественных опухолей, мукозиты, алопеция, тошнота и рвота [6]. Довольно часто встречаются воспаление и некротические процессы, развивающиеся вследствие проникновения противоопухолевых препаратов в ткани перитуморальной зоны [7]. Нередко возникает ситуация, когда цитотоксический препарат чрезвычайно эффективен при лечении конкретного рака, однако оптимально необходимая доза может быть недостижимой без чрезмерных побочных эффектов для пациента [8].…”

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Assessment of an antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in A-549 tumor cell subcutaneous xenografts

Lukbanova¹,

Zaikina²,

Sayapin

et al. 2021

Alʹm. klin. med.

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Rationale: Chemotherapy is one of the lung cancer treatment methods. The search for new substances with antitumor effect against malignant lung neoplasms is relevant because of low efficacy and side effects of cytotoxic agents. A promising substance class with various biological activities, including antitumor, includes alkaloids of the tropolone family, such as heptamerous non-benzoid aromatic compounds. 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone has been synthesized in Institute of Physical and Organic Chemistry; it is a new compound belonging to 2-quinoline-2-yl derivatives of 1,3-tropolone.Aim: To assess the antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone on subcutaneous xenografts of A-549 lung tumor cells in immunodeficient Balb/c Nude mice.Materials and methods: The study included 50 immunodeficient Balb/c Nude mice divided into 4 experimental groups depending on the dosage of the study substance (0.0055, 0.055, 0.55, and 2.75 mg/g); group 5 was the control group. A-549 cells of lung cancer were used as a xenograft. The antitumor effect of tropolone was evaluated by the inhibition of tumor growth and the index of tumor growth. The experiment lasted for 36 days starting from the first administration of the substances.Results: The mean tumor volumes on day 36 of the experiment in the control group and four experimental groups were 2729.5; 2150.8; 1746.4; 952.3 and 678.9 mm3 , respectively. The indices of tumor growth in groups 1, 2, 3 and 4 were significantly lower than in group 5 (control) starting from days 24, 21, 21 and 15, respectively, and till the end of the experiment. Maximal differences between groups 4 and 5 were observed at days 33 and 36 (by 3.7, p=0.01 and 4.1, p=0.003 times, respectively).Discussion: The anti-tumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone demonstrated in the study could be related to various mechanisms. For example, numerous studies have shown that its related compound hinokitiol exerts a cytotoxic effect associated with cessation of the cell cycle, apoptosis induction, DNA damage, and autophagic death of tumor cells.Conclusion: The study demonstrated significant differences in xenograft volumes in all experimental groups, compared to the control group. In mice, 2.75 mg/g bodyweight was the most effective dosage of the studied compound leading to a slow decrease in tumor growth rates and a decrease in the volumes of subcutaneous xenografts.

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Assessment of an antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in A-549 tumor cell subcutaneous xenografts

Lukbanova¹,

Zaikina²,

Sayapin

et al. 2021

Alʹm. klin. med.

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Glomerular filtration rate dynamics in patients with diffuse large B-cell lymphoma during induction immunopolychemotherapy

Nozdricheva,

Lysenko,

Guskova

et al. 2023

Onkogematologiâ

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Aim. To study the glomerular filtration rate (GFR) dynamics during induction immunopolychemotherapy (PCT) in patients with newly diagnosed diffuse large B-cell lymphoma. Materials and methods. The study included 39 patients with newly diagnosed diffuse large b-cell lymphoma who received specialized treatment in oncohematology department of national medical research centre for oncology (Rostov-on-Don). Patients underwent induction pct according to the R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, prednisolone) regimen with accompanying therapy (allopurinol). blood sampling was carried out at 0, 24, 48, 72, 120 hours and 21 days of the 1st PCT cycle. GFR was calculated using the SKD-epicre formula (chronic Kidney disease epidemiology collaboration creatinine-based). statistical data processing was carried out using the IBM SPSS statistics 23 program. Results. According to the gfr level before the start of chemotherapy (0 hours), the patients were divided into two groups: group a with GFR > 90 ml / min / 1.73 m2 and group b with GFR < 90 ml / min / 1.73 m2. In group a, there were no significant dynamic changes in the GFR level during PCT. Group B patients reacted more acutely to the administration of pct, which was manifested in an even greater decrease in the gfr level at 48 hours of PCT, and at 120 hours of PCT, the GFR approached the optimal values. on the 21st day from the start of the 1st pct course, the studied indicator returned to its initial values at 0 hour. further, the patients of these groups were divided into subgroups depending on the disease stage: group a consisted of 12 people with stages I–II and 15 people with stages III–IV. In group B, there were an equal number of patients with stages I–II and III–IV – 6 people. In group a, in patients with stages I–II and III–IV before the start of PCT (0 hours) and during PCT, there were no differences in the GFR level dynamics. In group B, patients with stages I-II and III–IV had similar GFR before the start of PCT, and during treatment, they reflected the previously noted general group trend in GFR level dynamics. Conclusion. The study found that in patients with initially low GFR level, a further, even more pronounced decrease in GFR during pct is observed. at the same time, the absence of significant differences in GFR level depending on disease stage allows us to conclude that the leading role is not so much the stage of the disease and tumor volume, but rather the initial functional status of the kidneys in the development of renal dysfunction in patients with diffuse large B-cell lymphoma during R-CHOP therapy.

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Study of biological activity of 2-quinoline-2-yl-derivative 1,3-tropolone in experiment

Lukbanova¹,

Dzhenkova²,

Гончарова³

et al. 2022

Issled. prakt. med. (Print)

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Purpose of the study. Was to reveal the antitumor effect of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone in subcutaneous PDX models of human lung cancer.Material and methods. The studied tropolone was synthesized using a method of expanding the o‑quinone cycle. Assess to it’s toxic effects was given by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient‑derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI %) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice.Results. An analysis of acute tropolone toxic effects did not reveal the lethal dose. The maximal TGI was observed on day 36 of the experiment in group 5 which have received 2.75 mg/g tropolone and accounted 73.5 % for females and 74.4 % for males. The average tumor volumes in females of this group were 431.3 ± 1,1 mm3 on day 33 of the experiment, in males – 428.9 ± 1,7 mm3 on day 30, and then the tumor volumes declined. The biochemical analysis of blood and histological examination of the tumor tissue of recipient mice reflect the severity of the antitumor effect on the dose of the studied tropolone.Conclusion. The research demonstrated the antitumor activity of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.

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Kidney Injury in Cancer Therapy

Cited by 7 publications

References 17 publications

Assessment of an antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in A-549 tumor cell subcutaneous xenografts

Assessment of an antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in A-549 tumor cell subcutaneous xenografts

Glomerular filtration rate dynamics in patients with diffuse large B-cell lymphoma during induction immunopolychemotherapy

Study of biological activity of 2-quinoline-2-yl-derivative 1,3-tropolone in experiment

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