Hereditary breast cancer is an autosomal dominant disease caused by variants in genes such as BRCA1/2, RAD51, ATM, BRIP1, and others. In a previous study using whole exome sequencing, we identified a germline variant of the LGR4 gene (rs34804482, NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly)) in a young Tuvan breast cancer patient (belonging to the Turkic-speaking tribes of Central Asia). The aim of this study was to determine the frequency of the variant of the LGR4 gene NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly) in ethnic groups of West Siberia using the PCR-RT method. The study involved 735 breast cancer patients from ethnic groups in Siberia, median age at diagnosis of 43 ± 15.6 years. The control group consisted of 727 healthy women from Siberia, median age of 43.05 ± 13.5 years. The frequency of this variant (rs34804482) was 0.015 in Russian, 0.022 in Buryat, and 0.069 in Tuvan breast cancer patients. In Tuvan women with breast cancer, the frequency of the LGR4 gene variant was significantly higher than in Russian BC patients (0.069 versus 0.015, X2 = 8.153, p = 0.005). The frequency of the LGR4 gene variant (rs34804482) in healthy Tuvan women was significantly higher than in healthy Russian women (0.066 versus 0.016, X2 = 6.368, p = 0.012). The variant frequency in healthy Russians was close to that in Europeans (0.016 versus 0.0219). We found no statistically significant differences in the rs34804482 frequency between breast cancer patients and healthy individuals in the ethnic groups studied. The highest frequency of this missense germline variant was observed among Tuvans.

Background. The results of the study of new imidazotriazine derivatives are presented to support their use as antitumor agents, including for breast cancer (BC) chemotherapy. The study is relevant due to the high prevalence and mortality of BC and other socially significant cancers. Antitumor drugs have limitations in their efficacy due to the primary or acquired drug resistance. As a result, 30% to 50% of patients do not receive adequate treatment, determining the need to develop new antitumor drugs. Aim. To evaluate the antitumor potential of 5 new imidazotriazine derivatives by testing their cytotoxic (CTA) and cytostatic (CSA) activity on BC cell cultures. Materials and methods. Culture of MCF-7, MDA-MB231, BT474, and MCF-10a cells and determination of CTA and CSA of imidazotriazine derivatives at concentrations ranging from 0.25 to 10.0 mmol/L. Results. For the MCF-7 culture, the maximum cell survival inhibition by the comparator (temozolomide) was 2.44, and the concentration causing 50% cell death (IC50) was 6.81 mmol/L; for other cell cultures, CTAs were slightly lower. Imidazotriazine 2 and imidazotriazine 3 showed values below or close to temozolomide; IC50 was not achieved in most cases. These two derivatives were considered to have low CTA and moderate CSA. Imidazotriazine 4 and imidazotriazine 5 showed higher activity than the comparator and were considered compounds with moderate CTA and CSA. Finally, imidazotriazine 1 showed the highest CTA and CSA values with a maximum cell survival inhibition of 4.35 and an IC50 of 1.94 mmol/L. Conclusion. Based on the results of the in vitro study, five new imidazotriazine derivatives have CTA and CSA in the following ascending order: imidazotriazine 2, imidazotriazine 3 temozolomide imidazotriazine 4 imidazotriazine 5 imidazotriazine 1. Therefore, 4-aminoimidazo[5,1-c][1,2,4]triazine-3,8-dicarboxylic acid diethyl ether (imidazotriazine 1) is the most promising new imidazotriazine derivative and is recommended for further preclinical studies.

Purpose of the study: to summarize the available data on the structure and function of EpCAM and its domains, their roles in promoting proliferation and epithelial-mesenchymal transition (EMT), contributing to cell stemness, and facilitating interactions with cell adhesion and invasion molecules.Material and Methods. A comprehensive search was conducted for articles in Russian and English within the scientifc databases PubMed, Scopus, Web of Science, and E-library. A total of seventy-nine articles ranging from 1996 to 2024 were utilized to compile this review.Results. This review summarized the pathogenetic and clinical signifcance of various EpCAM expression variants: EpCAM^high, EpCAM^low, and EpCAM^loss. It described the causes and mechanisms behind the loss of membrane EpCAM expression, each holding distinct biological and clinical implications. Features of EpCAM expression in normal epithelial tissues, during regeneration, and in dysplasia/ neoplasia as well as carcinomas were carefully outlined. The clinical implications of EpCAM expression remain a subject of debate; overexpression of EpCAM has been linked to both unfavorable and favorable prognoses. Special emphasis was placed on the expression variants of EpCAM in circulating tumor cells, disseminated cells, and carcinoma metastases.Conclusion. The pathogenetic and clinical signifcance of EpCAM expression in various nosological forms of carcinoma is complex and multifaceted. Weak expression or absence of EpCAM acts as independent factors infuencing the unique progression patterns of these diseases. Achieving a deeper understanding of the role of EpCAM in disease progression necessitates the simultaneous examination of both its extracellular and intracellular domains.

Introduction. Chemotherapy is a common treatment for breast cancer. Chemotherapeutic drugs effect blood monocytes, which are major contributors to cancer pathogenesis. However, to date, pro-tumor or anti-tumor programming by chemotherapy of monocytes is controversial.Aim. To characterize changes in phenotypic and transcriptomic profiles of monocytes of breast cancer patients before and after chemotherapeutic treatment.Materials and methods. In a cohort of 50 breast cancer patients, monocyte populations were identified based on their expression of CD14, CD16, CD163, and HLA-DR evaluated by flow cytometry before and after neoadjuvant chemotherapy. Bulk RNA sequencing was adopted to explore the transcriptomic profile of CD14+ monocytes before and after treatment. After treatment, we observed an increase in the activity of signaling pathways related to lipid metabolism and intracellular transport of vesicles from the endoplasmic reticulum, against the background of a decreased response to exposure to interferon γ and interferon α, and foreign molecules (exogenous nucleic acids, viruses and bacteria).Results. In breast cancer patients, neoadjuvant chemotherapy decreased in CD14+16+HLA-DR+ monocytes. Under cytostatic treatment, increased gene expression of MGLL, NR4A2, UCK1, YOD1, ABCA2, PAPSS2, ATP10 (log2FoldChange ≥0.8; false discovery rate (FDR) ≤0.01) and decreased gene expression of KPNA2, ERCC4, JAGN1, RUBCNL, SMYD4, B3GALT4 (log2FoldChange ≥0.8; FDR ≤0.01) were observed in monocytes of patients. Using discriminant analysis, the relative numbers of CD14+16–, CD14+16+, CD14-16+, CD14+16-HLA-DR+, CD14+16+HLA-DR+ and CD14–16+HLA-DR+ monocytes in the blood were found to be valuable in predicting response to neoadjuvant chemotherapy.Conclusion. Thus, association of blood monocytes with chemotherapeutic treatment in breast cancer was revealed.

The aim of the work is to study the effect of new azoloazine derivatives on the level of DNA damage to Vero cells (DNA comet test) in vitro by alkaline gel electrophoresis.Material and methods. The objects of the study are 8-(piperidinocarbonyl)3-cyclohexylimidazo[5,1-d][1,2,3,5]tetrazine-4(3H)-one (1), diethyl ether 4-aminoimidazo[5,1-c][1,2,4]triazine3,8-dicarboxylic acid (2), 4-amino-8-ethoxycarbonylimidazo[5,1-c][1,2,4]triazine-3-N-(p-toluyl)carboxamide (3). Epirubicin was chosen as a comparison drug. The compounds were used in doses of 1/2, 1/10 and 1/50 IC50. The Vero cell line cultured according to the standard protocol was selected as the cell model. To assess genotoxicity, an alkaline version of the DNA comet method was used, which has a high sensitivity and allows detecting DNA damage.Results. Analysis of the data obtained indicates that the tested compounds 1-3 enhance DNA damage in non-tumor cells. Compound 1 has the most pronounced genotoxic effect. Thus, the use of this substance in a dose of ½ IC50 led to a significant increase in the length of the comet’s tail by 1.5 times. It was noted that DNA damage under the action of compound 1 in the studied doses and of epirubicin was on the same level.Conclusions. The results obtained prove that compounds 1-3 may have a potentially carcinogenic effect. However, this assumption requires further in-depth experimental studies.

The purpose of this study was to investigate the effect of new azoloazine derivatives on the level of DNA damage in Vero cells in vitro using alkaline gel electrophoresis (DNA comet assay). The objects of research were (1) 8-(piperidinocarbonyl)-3-cyclohexylimidazo[5,1-d][1,2,3,5]tetrazine-4(3N)-one, (2) 4‑aminoimidazo[5,1-c][1,2,4]triazine-3,8-dicarboxylic acid, and (3) 4-amino-8-ethoxycarbonylimidazo[5,1-c][1,2,4]triazine-3-N-(P-toluyl)carboxamide. Epirubicin was chosen as a comparison drug. Compounds were used in doses of 1/2, 1/10, and 1/50 IC50. The Vero cell line, cultured according to standard protocol was used as the cell model. To assess genotoxicity, an alkaline version of the comet assay, which is highly sensitive and allows the detection of DNA damage was used. Analysis of the obtained data indicates that tested compounds 1–3 increase the amount of DNA damage in nontumor cells. Compound 1 has the most pronounced genotoxic effect. Thus, using this compound at a dose of 1/2 IC50 led to a significant increase in the comet tail length by 1.5 times. It was noted that the amount of DNA damage caused by the action of compound 1 at the studied doses and epirubicin was on the same level. The results obtained show that compounds 1–3 may be potentially carcinogenic. However, this conclusion requires further in-depth experimental stud-ies.

Whole exome sequencing of peripheral blood samples from Tuvan females diagnosed with breast and ovarian cancers (BC/OC) was performed to search for new genes involved in BC/OC pathogenesis. Considering the high cost of whole exome sequencing and study material requirements, 9 samples were selected from 61 genomic DNA samples. A mutation in the LGR4 gene (rs34804482) involved in the tumor-mediated Wnt signaling pathway and a mutation in the BRWD1 gene (rs147211854) involved in chromatin remodeling were identified in BC patients. A mutation in the CITED2 gene (rs77963348) involved in the pathogenesis of primary ovarian insufficiency was identified in a patient with OC and a history of infertility. A mutation in the PDGFRA gene (rs2291591) was identified in two BC/OC patients. LRG4, BRWD1, PDGFRA, and CITED2 germline pathogenic mutations were discovered in Tuvan women diagnosed with BC/OC for the first time.

Hereditary breast cancer (HBC) is a heterogeneous disease caused by mutations in genes characterized by ethnic specifcity. The clinical heterogeneity of this disease signifcantly complicates its diagnosis. The use of high-throughput sequencing is one of the approaches that allow the search for genes and their variants associated with the development of HBC. The purpose of the study was to search for new genes associated with HBC in the understudied ethnic groups of Siberia by using whole exome sequencing (WES).Material and Methods. WES was performed on a cohort of 16 probands with BC (Tuvan, Yakut, Altai ethnos). The study material was genomic DNA isolated from peripheral blood leukocytes. Libraries were prepared using a BGI Optimal DNA Library Prep kit. An Agilent SureSelect Human All Exon V6 kit was used for hybridization. High-throughput sequencing was performed on a DNA nanoball sequencing platform (DNBSeq-G400).Results. In the overall group of patients with signs of HBC, pathogenic variants were detected in 12.5 % of cases (2/16). For the frst time, BRCA1 (rs80357635) pathogenic variant was identified in a young patient with metachronous BC (Yakut ethnic group). A pathogenic variant of the ATM gene (rs780619951 NM_000051:exon16:c.C2413T:p.R805X) was identified in a young patient with BC (Tuvinian ethnic group). A pathogenic variant of the TDP2 c.G4T:p.E2X, rs770844602 gene (DNA repair gene) was identified for the frst time in a Tuvan BC patient (metachronous) with a family history, but its contribution to HBC remains to be proven. The TDG gene variant (rs764159587 NM_001363612:exon7:c.536dupA:p.E179fs) found in the Tuvan ethnic group and affecting splicing (SpliceAI: 0.580) requires special attention.Conclusion. This report is the frst to describe the germinal variant in the BRCA1 (rs80357635) gene in the Yakut ethnic group. Further studies are required to confrm pathogenicity of germinal variants in non-well studied genes TDP2, TDG in ethnic BC patients.

Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno-oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte activity against transformed cells, a tumor can escape immune surveillance and leverage chronic inflammation to maintain its own development. Research on antitumor immunity primarily focuses on the role of the tumor microenvironment, whereas the systemic immune response beyond the tumor site is described less thoroughly. Here, a comprehensive review of the formation of the immune profile in breast cancer patients is offered. The interplay between systemic and local immune reactions as self-sustaining mechanism of tumor progression is described and the functional activity of the main cell populations related to innate and adaptive immunity is discussed. Additionally, the interaction between different functional levels of the immune system and their contribution to the development of the pro- or anti-tumor immune response in BC is highlighted. The presented data can potentially inform the development of new immunotherapy strategies in the treatment of patients with BC.

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients. However, its efficacy is extremely limited in microsatellite stability (MSS)/mismatch repair proficient (pMMR) patients. We report a case of a 42-year-old man diagnosed with MSS/pMMR mCRC who has achieved a durable response to nivolumab after a progression under chemotherapy with antiangiogenic treatment. We observed for the first time an atypical response after 8 months of nivolumab treatment, with the regression of previous primary pulmonary lesions and the presence of new para-aortic lymph node lesions. This report demonstrates that a subset of pretreated mCRC patients with the MSS/pMMR phenotype may benefit from nivolumab and these patients need more attention.

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various “scenarios” of the precancerous process: isolated BCH→stopping at the stage of hyperplasia, BCH+SM→progression of hyperplasia into metaplasia, SM+dysplasia→progression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various “scenarios” of the precancerous process in the bronchial epithelium.

Background: Hereditary breast cancer (BC) is an autosomal dominant disease caused by mutations in genes such as BRCA1/2, BRAD1, RAD54L, RAD51, ATM, BRIP1, and others. The prevalence and range of mutations can differ among various regions and ethnic groups. In a previous study using whole exome sequencing, we identified a germline pathogenic variant of the LGR4 gene (rs34804482, NM_018490.3: c.2531A>G) in a young Tuvan BC patient (belonging to the Turkic-speaking tribes of Central Asia). The aim of this study was to determine the frequency of the germinal pathogenic variant rs34804482 of the LGR4 gene (NM_018490.3: c.2531A>G) in ethnic groups of West Siberia (comparing BC patients and healthy subjects) using the PCR-RT method. Methods: The study involved 735 BC patients from various ethnic groups in Siberia, including Russians, Buryats, Tuvans, Yakuts, Altaians, and Khakassians, with a median age at diagnosis of 43±15.6 years. The control group consisted of 727 healthy women from the same ethnic groups in Siberia, with a median age of 43.05±13.5 years. Results: In a general group of BC patients, the frequency of the pathogenic variant of the LGR4 gene (rs34804482) was 0.027. Specifically, the frequency of this variant was 0.015 in Russian BC patients, 0.022 in Buryat BC patients, and 0.069 in Tuvan BC patients. This variant was not detected in Khakassian and Yakut BC patients. In Tuvan women with BC, the frequency of the pathogenic variant of the LGR4 gene was significantly higher than in Russian BC patients (X2 = 8.153, p = 0.005). The frequency of the pathogenic variant of the LGR4 gene (rs34804482) in healthy Tuvan women was significantly higher than in healthy Russian women (0.066 versus 0.016, X2=6.368, p=0.012). The mutation frequency in healthy Russians was close to that in Europeans (0.016 versus 0.0219). The highest frequency of this pathogenic variant was found among healthy Tuvans (0.066), significantly higher compared to Americans (0.0000) and other ethnic groups (according to ExAc). Conclusions: Our study was the first to investigate the frequency of the pathogenic variant of the LGR4 gene (rs34804482) in different ethnic groups of Siberia, comparing BC patients with healthy individuals. We found no statistically significant differences in the mutation frequency between BC patients and healthy individuals in the ethnic groups studied. The highest frequency of this pathogenic variant was observed among healthy Tuvans (0.066), which was significantly higher compared to other ethnic groups.

One of the predictors of adverse prognosis in breast cancer is the overexpression of the EpCAM protein. However, a signifcant part of tumor cells have low or no EpCAM expression. The molecular features and the ability to grow in 2D and 3D cultures, indirectly refecting metastatic potential of tumor cells without EpCAM expression, have not been sufficiently studied.The aim of the study was to compare phenotypic variants of stem cells and EMT depending on the EpCAM expression in the primary tumor of breast cancer and 2D and 3D cultures.Material and Methods. The study included 7 patients with invasive breast carcinoma of no special type. Luminal A subtype was found in 2/7 patients (29 %), and luminal B HER2-negative molecular subtype was found in 5/7 patients (71 %). The patients didn’t have neoadjuvant chemotherapy. Cells from the primary tumor were cultured in 2D and 3D. The primary tumor cells, 2D and 3D cultures were phenotyped using fow cytometry with antibodies targeting: CD45, EpCAM (CD326), CD44, CD24, N-cadherin (CD325), and CD133, CK7/8, EpCAM (CD326).Results. No significant differences were found in the frequency of detection and the number of cells exhibiting stem cell features among EpCAM- and EpCAM+ tumor cells, 2D and 3D cultures. All phenotypic variants of co-expression of stemness markers CD44, CD24, CD133, and ALDH were present both in the primary tumor and 2D/3D cultures. Stem cells in mammospheres had features of both epithelial and hybrid EMT phenotypes. In primary tumors and 2D/3D cultures, the smallest proportion consisted of stem cells with the CD44+CD24- phenotype and cells co-expressing CD44+CD24- with other stemness markers, while the largest proportion comprised stem cells with ALDH+ and ALDH+CD133+ phenotypes. Marked intra- and inter-tumor heterogeneity in the phenotypic composition of primary tumors, 2D, and 3D cultures was noted.Conclusion. The results indicate that EpCAM-negative and EpCAM-positive tumor cells of luminal molecular subtype of breast cancer are capable of exhibiting various phenotypic variants of stemness and EMT in the primary tumor and 2D and 3D cultures. In most cases, individual tumor cells show co-expression of several stemness markers. The phenotypic composition of primary tumors, 2D and 3D cultures is characterized by pronounced intra- and inter-tumor heterogeneity.

OBJECTIVE:The BRCA1/2 mutation status testing is the global standard of care for breast cancer patients with a family history of cancer. BRCA1/2 mutations are known to be ethno-specific. For some ethnic groups of the Northern Asia (Buryats, Yakuts, Altaians, Tuvans, Khakasses, etc.) the founder mutations in the BRCA1/2 genes have not been revealed. This systematic review was conducted to assess the prevalence of BRCA1/2 mutation in breast cancer patients inhabiting Eastern Europe and Northern Asia (or Siberia). METHODS:A total of 23,561 studies published between 2014 and 2024 were analyzed, of which 55 were included in the review. The literature search was conducted using RusMed, Cyberleninka, Google Scholar, eLibrary, NCBI databases (n=5) and conference papers. RESULTS:The founder mutations (c.5266dupC and/or c.181T>G) of BRCA1 gene that were frequently observed in the Slav peoples were also identified in Chechens, Armenians, Bashkirs, Ukrainians, Mordovians, Mari, Kabardians, Tatars, Uzbeks, Kyrgyz, Ossetians, Khanty indigenous peoples and Adygs. For Chechens, Kabardians, Ingush, Buryats, Khakasses, Sakha, Tuvans and Armenians, rare pathogenic variants of the BRCA1/2, ATM, СНЕК2, BRIP1, NBN, PTEN, TP53, PMS1, XPA, LGR4, BRWD1 and PALB2 genes were found. No data are available about the frequency of pathogenic BRCA1/2 mutations for ethnic groups, such as the Udmurts, Komi, Tajiks, Tabasarans, and Nogais indigenous people. CONCLUSION:This is the first systematic review that provides the spectrum of BRCA mutations in ethnic groups of breast cancer patients inhabiting Eastern Europe and Northern Asia. It has been shown that the mutations are ethnospecific (varied widely within groups) and not all groups are equally well studied. Further studies on the ethnic specificity of BRCA gene mutations are required.

Following the discovery of circulating tumor cells (CTCs) in the peripheral blood of cancer patients, CTCs were initially postulated to hold promise as a valuable prognostic tool through liquid biopsy. However, a decade and a half of accumulated data have revealed significant complexities in the investigation of CTCs. A challenging aspect lies in the reduced expression or complete loss of key epithelial markers during the epithelial-mesenchymal transition (EMT). This likely hampers the identification of a pathogenetically significant subset of CTCs. Nevertheless, there is a growing body of evidence regarding the prognostic value of such molecules as CD24 expressing in the primary breast tumor. Herewith, the exact relevance of CD24 expression on CTCs remains unclear. We used two epithelial markers (EpCAM and cytokeratin 7/8) to assess the count of CTCs in 57 breast cancer patients, both with (M0mts) and without metastasis (M0) during the follow-up period, as well as in M1 breast cancer patients. However, the investigation of these epithelial markers proved ineffective in identifying cell population expressing different combinations of EpCAM and cytokeratin 7/8 with prognostic significance for breast cancer metastases. Surprisingly, we found CD24+ circulating cells (CCs) in peripheral blood of breast cancer patients which have no epithelial markers (EpCAM and cytokeratin 7/8) but was strongly associated with distant metastasis. Namely, the count of CD45-EpCAM-CK7/8-CD24+ N-cadherin—CCs was elevated in both groups of patients, those with existing metastasis and those who developed metastases during the follow-up period. Simultaneously, an elevation in these cell counts beyond the established threshold of 218.3 cells per 1 mL of blood in patients prior to any treatment predicted a 12-fold risk of metastases, along with a threefold decrease in distant metastasis-free survival over a 90-month follow-up period. The origin of CD45-EpCAM-CK7/8-CD24+ N-cadherin—CCs remains unclear. In our opinion their existence can be explained by two most probable hypotheses. These cells could exhibit a terminal EMT phenotype, or it might be immature cells originating from the bone marrow. Nonetheless, if this hypothesis holds true, it's worth noting that the mentioned CCs do not align with any of the recognized stages of monocyte or neutrophil maturation, primarily due to the presence of CD45 expression in the myeloid cells. The results suggest the presence in the peripheral blood of patients with metastasis (both during the follow-up period and prior to inclusion in the study) of a cell population with a currently unspecified origin, possibly arising from both myeloid and tumor sources, as confirmed by the presence of aneuploidy.

The genotoxic properties of three new azoloazine derivatives (azoloazines 1 – 3 ) exhibiting cytotoxic activity were studied in an in vitro experiment using MCF-7 human breast cancer cell culture. Acomparison of the effects of azoloazines 1 – 3 at doses of 1/2, 1/10, and 1/50 of IC 50 with those of epirubicin at the same doses on the main indicators of damage to the genetic apparatus of the cells revealed that the studied compounds had the greatest toxic effect on DNAat a dose 1/10 of IC 50 . The genotoxicity of azoloazines 1 – 3 at a dose 1/10 of IC 50 was shown to exceed that of epirubicin.

Решение об открытии в Томске филиала Онкологического научного центра Академии медицинских наук СССР было принято 3 января 1979 г. Государственным комитетом СССР по науке и технике, а уже 8 января 1979 г. министром здравоохранения СССР академиком АМН СССР Б.В. Петровским был подписан Приказ № 20 «Об организации в г. Томске Сибирского филиала Онкологического научного центра АМН СССР».

Colorectal cancer has been one of the leading malignant neoplasms in males and females over many years. The vast majority of patients (70%) with colon lesions develop distant metastases to the liver, which are the main cause of death.