Russian Journal of Oncology

Peer-review bimonthly medical journal.


Editor-in-chief

Publisher & founder

About

Since 1996 the journal publishes original articles and reviews that cover current achievements in the fields of clinical and experimental oncology as well as practical aspects of diagnosis and comprehensive treatment of malignant tumors. The journal offers insights into actual experience of cancer centers, discusses the current state of oncology research and practice outside Russia, and facilitates experience exchange. The journal also publishes medical news and material on the implementation of scientific discoveries, the most essential theoretical and practical issues, and the history of oncology.

The journal is aimed at a wide range of medical professionals: oncologists, surgeons, general practitioners, and public health officials focusing on the diagnosis and treatment of cancers.

Types of accepted articles

  • reviews
  • systematic reviews and metaanalyses
  • original research
  • clinical case reports and series
  • letters to the editor
  • short communications

 

Publications

  • in English and Russian
  • bimonthly, 6 issues per year
  • continuously in Online First
  • with NO Article Processing Charges (APC)
  • distribution in hybrid mode - by subscription and/or Open Access
    (OA articles with the Creative Commons Attribution 4.0 International License (CC BY-NC-ND 4.0))

Indexation

  • Russian Science Citation Index 
  • Embase
  • Google Scholar
  • Ulrich's Periodicals Directory
  • Dimensions
  • Portico
  • Crossref

 

Current Issue

Open Access Open Access  Restricted Access Access granted  Restricted Access Subscription or Fee Access

Vol 28, No 1 (2023)

Cover Page

Full Issue

Open Access Open Access
Restricted Access Access granted
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Original Study Articles

Cytotoxic and Anticancer Activity of Pharmacological Pairs of C115H Methionine–Gamma-lyase and S-Propyl-L-Cysteine Sulfoxide
Abo Qoura L., Karshieva S.S., Borisova J.A., Pokrovsky V.S.
Abstract

BACKGROUND: One of the alternate ways to developing novel medication is to use pharmacological pairs: an enzyme and a non-toxic prodrug that, under certain conditions, releases cytotoxic substances within or on the surface of the cancer cells, allowing the drug to be delivered precisely to the cancer cells.

AIM: To evaluate cytotoxic and anticancer effects of the pharmacological pair of C115H methionine-γ-lyase (C115H MGL), conjugated with daidzein (C115H MGL-Dz), and S-propyl-L-cysteine sulfoxide (propiin) against different kinds of solid tumors in vitro and in vivo.

METHODS: MTT-test was performed to determine the cytotoxicity of C115H MGL-Dz in the presence of propiin in vitro against human embryonic kidney (HEK-293), human placenta, breast cancer (MCF7, SKBR3, and T47D), colon cancer (HT29 and COLO205), pancreatic cancer (MIA PaCa-2) and prostate cancer (DU145, and PC3) cells. The anticancer activity of the pharmacological pair "C115H MGL-Dz + propiin" against SKBR3, MIA PaCa-2, and HT29 in vivo was investigated using subcutaneous xenografts in BALB/c nude mice.

RESULTS: In comparison to dipropylthiosulfinate generated in vitro using the pharmacological pairs "C115H MGL + propiin", targeted delivery of C115H MGL-Dz as a component of a pharmacological pair "C115H MGL-Dz + propiin" to generate dipropylthiosulfinate directly on the surface of cancer cells enhances cytotoxicity in all cancer cells. The study of the antitumor activity of the pharmacological pair "C115H MGL-Dz + propiin" in vivo revealed a suppression of tumor volume growth in xenografts SKBR3 (tumor growth inhibition, TGI=89%, p=0.004), MIA PaCa-2 (TGI=50%, p=0.011), and HT29 (TGI=52%, p=0.04) vs control.

CONCLUSIONS: On several cancer cells, the cytotoxicity and anticancer activity of dipropylthiosulfinate produced by the pharmacological pair "C115H MGL-Dz + propiin" was observed. Our findings may stimulate more study into the role of pharmacological pairs as a novel strategy to cancer treatment.

Russian Journal of Oncology. 2023;28(1):5-14
pages 5-14 views
Preclinical positron emission computed tomography of prolonged tumor growth after lutetium-177 prostate-specific membrane antigen treatment in xenograft model of human prostate cancer
Klementyeva O. ., Lipengolts A.A., Grigorieva E.Y., Smirnova A.V., Finogenova Y.A., Shpakova K.E., Skribitsky V.A., Lagodzinskaya Y.S.
Abstract

BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. They will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to prostate-specific membrane antigen (PSMA) labeled with lutetium-177.

AIM: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy.

METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. Positron emission computed tomography with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA-I&T.

RESULTS: Positron emission tomography imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq of [177Lu]Lu-PSMA-I&T, which is equivalent to minimal human therapeutic dose (28.6 MBq/kg).

CONCLUSIONS: The study confirmed the short period of the observed therapeutic effect after a single injection of 9.2 MBq of [177Lu]Lu-PSMA-I&T. The tumor regrowth in 2.5 months after the reduction of 22Rv1 xenografts to a non-palpable state was confirmed by positron emission computed tomography with 18F-PSMA-1007. These results confirm the need to study the frequency of repeated administrations of radiopharmaceuticals based on ligands to PSMA labeled with lutetium-177 to achieve a stable therapeutic effect in cases where a single dose reduction is necessary.

Russian Journal of Oncology. 2023;28(1):15-26
pages 15-26 views
PC Kz is the novel human prostate cancer model in vitro and in vivo
Sokolova D.V., Khan I.I., Zhdanov D.D., Demidova E.A., Krivchenko V.O., Aidossov C., Pokrovsky V.S.
Abstract

BACKGROUND: The use of relevant in vitro and in vivo model systems is important in preclinical studies of anticancer agents. The process of creating tumor models is methodically complicated and has a number of disadvantages. Among tumor models of prostate cancer, the most accessible are 2D models (DU145, 22Rv1, PC3, LNCaP, VCaP cell lines), their xenograft models in immunodeficient mice and some patient-derived xenograft models. However, this panel of experimental models is not perfect and needs further expansion.

AIM: To create a new preclinical prostate cancer model, characterize it (morphology, tumorigenicity, tumor growth kinetics in vivo, verification of prostate-specific membrane antigen expression status, testosterone production, sensitivity to CYP17A1 inhibitors), and develop resistance to the steroid CYP17A1 inhibitor — abiraterone.

METHODS: CYP17A1 expression in PC Kz cell line was evaluated by reverse transcription polymerase chain reaction. Testosterone concentration was determined with an enzyme-linked immunosorbent assay. The sensitivity to antitumor agents was studied with the MTT test. Tumorigenicity was evaluated by transplantation of PC Kz cell line into Balb/c nude mice. The prostate-specific membrane antigen expression status was assessed using the indirect reaction of surface immunofluorescence.

RESULTS: The PC Kz cell line is characterized by a high level of CYP17A1 messenger RNA expression, comparable to that of the commercial 22Rv1 cell line. Immunophenotypic analysis demonstrated negative prostate-specific membrane antigen expression status of PC Kz cell line. A significant decrease (18%) in testosterone concentration in vitro was found, compared to the value in the control. This effect can be associated with the suppression of CYP17A1 gene expression.

The studied PC Kz cell line is tumorigenic in Balb/c nude mice (100% tumorigenicity was detected during the first passage at a transplantation dose of 107 cells/mouse). A pathomorphological study of the structures of the obtained subcutaneous PC Kz xenografts verified their identity to the histological image of human prostate cancer. Furthermore, PC Kz/AA cell line was obtained, resistant to abiraterone; the index of resistance was 3.4.

CONCLUSION: The derived PC Kz cell line was adapted for in vitro and in vivo growth, characterized by the main biological parameters, and can be recommended as an adequate test system to use in preclinical studies of new antitumor agents for the human prostate cancer treatment.

Russian Journal of Oncology. 2023;28(1):37-52
pages 37-52 views
The effect of NBS1 heterozygous inactivating mutation in a model of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mice
Yurova M.N., Golubev A.G., Fedoros E.I., Tumanyan I.A., Von Y.D., Semenov A.L., Otradnova E.A., Imyanitov E.N.
Abstract

BACKGROUND: The creation of new experimental models carrying various heterozygous inactivating mutations in DNA repair genes and their carcinogenesis studies could expand our understanding of the spectrum of possible neoplasms that patients with such mutations are at risk of developing.

AIM: The study of the effect of NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) in a model of 7,12-dimethylbenz[a]anthracene (DMBA) induced carcinogenesis in mice.

MATERIALS AND METHODS: Carcinogenesis was induced in 2-month-old female mice with and without NBS1 heterozygous mutation by intragastric administration of 7,12-DMBA (dose of 50 mg/kg once a week, for 8 weeks) on a high-fat diet. Lifetime observation was conducted, and parameters of lifespan and carcinogenesis were evaluated.

RESULTS: NBS1 inactivating heterozygous mutation had no significant effect on the incidence of tumor pathology induced by 7,12-DMBA, but somewhat accelerated the rate of tumor development and, consequently, the death of animals. The presence of the mutation increased the sensitivity to carcinogen toxic effect, which was expressed in a statistically significant increase in death rate (by 35%) in the early stages of the study. The mean lifespan in female NBS1 mutant mice was reduced by 14% compared to mutation-free animals.

CONCLUSION: Carrying NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) worsens the prognosis of survival in the model of chemically induced 7,12-DMBA carcinogenesis in mice.

Russian Journal of Oncology. 2023;28(1):27-36
pages 27-36 views
Antiproliferative activity of the novel CYP17A1 inhibitor alsevirone
Khan I.I., Latysheva A.S., Zolottsev V.A., Demidova E. ., Spirina T.S., Karshieva S.S., Sokolova D.V., Yakunina M.N., Komarova M.V., Misharin A.Y., Pokrovsky V.S.
Abstract

BACKGROUND: Prostate cancer is the most frequently diagnosed type of cancer in men in developed countries. It is dependent upon androgens and could be effectively combated by androgen deprivation therapy. Reduction of androgen synthesis can be accomplished through the inhibition of the enzyme 17α-hydroxylase/17.20-lyase (CYP17A1), which catalyzes two sequential reactions in the production of androgens. Steroid derivatives modified with nitrogen-containing heterocycles attract attention as antineoplastic agents for prostate cancer treatment due to their inhibitory potential against CYP17A1.

AIM: Evaluate cytotoxic activity and antitumor effects of the synthesized alsevirone in comparison with abiraterone.

METHODS: Cytotoxicity was evaluated using MTT test. Anticancer effect was researched in vivo in prostate cancer xenograft models 22Rv1 and DU145 in Balb/c nude mice. Testosterone concentration was determined using an enzyme-linked immunosorbent assay in blood serum of BDF1 mice.

RESULTS: Alsevirone demonstrated cytotoxic activity in prostate cancer cells: DU145 (23.8±1.2 µM vs 151.4±23.7 µM for abiraterone), 22Rv1 (35.9±5.6 µM vs 109.9±35.2 µM for abiraterone) and LNCaP (22.9±0.5 µM vs 28.8±1.6 µM for abiraterone). Testosterone concentration in blood serum of BDF1 mice reduced by 80% after 10-day treatment. Inhibition of the tumors’ growth in 22Rv1 xenograft model was statistically significant when using alsevirone in comparison with the control group: average tumor volume was 171.6±50.1 mm3 (р=0.022) vs 424.2±70.3 mm3 in control, with tumor growth inhibition index of 59%.

CONCLUSIONS: Alsevirone has a higher cytotoxic potential against prostate cancer cells (DU145, LNCaP and 22Rv1) compared to abiraterone. Alsevirone demonstrated the ability to reduce the concentration of testosterone in the blood serum of BDF1 mice, and statistically significant antitumor activity in 22Rv1 xenograft models.

Russian Journal of Oncology. 2023;28(1):53-64
pages 53-64 views

Reviews

Three-dimensional cell models for studying tumor–immune interactions and testing immunotherapeutic drugs
Filippova S.Y., Timofeeva S.V., Mezhevova I.V., Shalashnaya E.V., Rozenko L.Y., Shaposhnikov A.V., Novikova I.A.
Abstract

One of the most promising approaches to cancer treatment is immunotherapy. Suppression of immune checkpoints in tumor tissue (anti-CTLA4, anti-PD1) using monoclonal antibodies has increased the overall survival of patients with some forms of skin melanoma and lung cancer. However, the percentage of patients responding to treatment varies from 20% to 40% depending on the type of cancer and the expression of target molecules by the tumor. The main source of failure of immunotherapy is the tumor microenvironment, which affects both tumor cells and immune cells, causing them to adapt to immunotherapeutic drugs. It is known that the architecture and cellular composition of the microenvironment act on various tumor parameters, promoting the recruitment of immunosuppressive cells into the tumor tissue, as well as the expression of checkpoint inhibitors, such as PD-L1, by tumor cells. Therefore, the complex composition of the tumor microenvironment must be taken into account when searching for new therapies and stratifying patients who may respond to immunotherapy. Therefore, in immunooncological studies, it is necessary to use three-dimensional cellular models that more fully reflect the architecture and cellular composition of the tumor. In this review, we evaluate three-dimensional cell models as tools for research in the field of immuno-oncology, as well as for personalized treatment selection, the search for new targets, and the optimization of existing cancer immunotherapies.

Russian Journal of Oncology. 2023;28(1):65-78
pages 65-78 views
The use of L-asparaginase for the treatment of solid tumors: data from experimental studies and clinical trials
Kislyak I.A., Pokrovskaya M.V., Zhanturina D.Y., Pokrovsky V.S.
Abstract

Drug therapy is one of the main strategies of cancer treatment. L-asparaginase, the enzyme that hydrolyzes asparagine, has been included in the treatment regimens for acute lymphoblastic leukemia and other hematological malignancies since more than 50 years ago, but its use for the treatment of solid tumors is still extremely limited. This review analyzes experimental data on the sensitivity of cell lines and xenografts of solid tumors to L-asparaginase, examines the results of clinical trials. Among the mechanisms of the cytotoxic effect of L-asparaginase on tumor cells, such processes as depletion of aspartic and glutamic acids, influence on the internal and external pathways of apoptosis, inhibition of cellular processes through a decrease in the activity of the mTOR protein, and weakening of the expression of the telomerase gene are discussed. Separately, molecular markers are considered, which can be used to suggest the effectiveness of future therapy with L-asparaginase in solid tumors. These markers include expression levels of asparagine synthetase and glutamine synthetase genes, degree of methylation of the ASNS gene promoter region, PTEN protein activity and autophagy, bone marrow environment of tumor cells, as well as expression of genes associated with asparaginase resistance (such as the μ1 opioid receptor gene and the huntingtin-associated protein 1 gene).

Russian Journal of Oncology. 2023;28(1):79-94
pages 79-94 views


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