Статьи журнала - Сибирский онкологический журнал
Все статьи: 3854
Статья научная
Using DIC and confocal microscopy, changes in morphology, migratory characteristics and adherence junctions (AJs) were analyzed in the mammary carcinoma cell line MCF-7-SNAI1 after activation of the EMT transcription factor SNAI1. Western blot analysis showed that after removal of tetracycline from the cell culture medium expression of SNAI1 reached its peak in 24 hours and then plateaued for 7 days. During the 7 days the cells continued to express E-cadherin; however, tangentialAJs typical for cells with stable cell-cell adhesion, changed into radial AJs. The radial AJs continued to accumulate E-cadherin during 24-72 hours after tetracycline removal. As a result of SNAI1 activation, the cells underwent epithelial-mesenchymal transition (EMT) and became migratory. On a two-dimensional substrate, cells exhibited both individual and collective migration. As the tetracycline washout period progressed, the fraction of the cells capable of migrating through migration chamber membranes increased; on the contrary, cells’ ability to invade an epithelial monolayer decreased. These results demonstrate that retaining a hybrid epithelial/mesenchymal phenotype and accumulation of E-cadherin in AJs during early stages of EMT do not impede disruption of stable cell-cell adhesion and cells’ acquisition of migratory activity.
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Influence of immune targeted therapy on immune system parameters in patients with endometrial cancer
Статья научная
Immune targeted therapy (ITT) including pembrolizumab, an immune checkpoint inhibitor, and lenvatinib, a targeted drug that blocks receptor tyrosine kinases, is one of the main treatment strategies for advanced endometrial cancer (aEC) patients with proficient mismatch repair (pMMR) and microsatellite stable (MSS). Since immunological mechanisms are involved in the implementation of the therapeutic effects of pembrolizumab and lenvatinib, it is likely that the current state of the patients’ immune system affects the efficacy of ITT. The purpose of the study was to investigate changes in peripheral blood immune parameters depending on the response to therapy in aEC patients who received therapy with pembrolizumab and lenvatinib. Material and Methods. The study included 12 patients with stage II–IV (T2–4N0–2M0–1) aEC with pMMR and MSS, who received therapy with combination of pembrolizumab and lenvatinib. All patients were divided into 2 groups: 1) with disease progression within 6 months of starting ITT (n=4), 2) without signs of progression for more than 6 months (n=8). The immune parameters (the number of VEGFR+ monocytes and VEGFR expression on monocytes, the number of PD-1+ cells in peripheral blood and PD-1 expression on them, the lymphocyte subsets) were evaluated by flow cytometry before starting ITT, 2 and 6 months after therapy. The control group consisted of 39 patients with newly diagnosed EC prior to anticancer therapy. Results. ITT resulted in significant changes in the number of VEGFR+ monocytes and VEGFR expression on monocytes, as well as in the number of PD-1+ cells in peripheral blood and PD-1 expression on them, along with alterations in the lymphocyte subsets. Changes in the immune parameters were related to the response to ITT. At the point of outcome (during disease progression or in the case of long-term response to therapy) the difference in the parameters reached the level of statistical significance. In the case of effective ITT, the immune parameters approached the values observed in control group patients with EC being newly diagnosed. Conclusion. Changes in immune system parameters of aEC patients treated with pembrolizumab in combination with lenvatinib were found to be related to response to therapy.
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KRAS-мутированный немелкоклеточный рак легкого: новые стратегии терапии
Статья научная
Рак легкого остается одним из наиболее опасных и распространенных видов онкологических заболеваний, требующих постоянного совершенствования методов диагностики и лечения. легкого В попытке добиться большей эффективности для отдельных групп пациентов генетическая неоднородность рака заставляет искать новые терапевтические мишени. Цель исследования - обновление текущих знаний об аденокарциноме легкого с мутацией в гене KRAS, рассмотрение новых возможностей персонализированного лечения KRAS-мутированного НМРЛ и формирование образа российского пациента, которому потенциально показана таргетная терапия. Материал и методы. Проведен поиск доступных литературных источников, опубликованных в базе данных Pubmed, Cochrane Library, Elibrary, включались публикации, относящиеся к 2008-2023 гг.
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Laparoscopic partial nephrectomy with intra-arterial cold perfusion. What can go wrong?
Статья научная
Introduction. In kidney masses of a high nephrometric index, a variant of renal ischemia is mostly needed, and to increase the time of compression of the renal artery, the cold renal ischemia may be relevant. Advantages of intra-arterial cold perfusion (IACP) are: good visualization and uniform cooling of the entire thickness of the renal parenchyma. This approach is not without its own set of challenges and potential complications during and after surgery. Purpose: to describe complications during kidney resection under IACP and options for their resolution with the practical recommendations based on literature data and clinical cases from our center. Material and Methods. The study included 14 patients with kidney masses of a high nephrometric index (RENAL 10 or more), who underwent kidney resections as an experimental technique under IACP from 2021 to 2024 at P.A. Hertzen Moscow Cancer Research Institute. Results. We identified both intra- and postoperative complications in 6 cases: perforation of the renal artery (n=1), brachial artery thrombosis (n=1), thrombosis of the renal artery (n=1), air embolism of segmental branches of the renal artery (n=2), urine leakage (n=1). Conclusion. The IACP-associated intraoperative complications in our cohort diminished over time as familiarity with the technique improved. The IACP is workable, efficient, and holds promise, indicating its appropriateness for large, well-equipped centers. In patients with just one functioning kidney and high nephrometric index masses needing prolonged ischemia during removal, this technique could become a lifesaving option as expertise grows.
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Статья научная
In vivo autofluorescence of normal and metaplastic epithelium of esophagogastric transition in patients with reflux-esophagitis was studied by local fluorescence spectroscopy under 532 nm excitation. It was shown that application of in vivo local fluorescence spectroscopy during gastroesophagoscopy makes it possible to improve a quality of diagnostics of Barrett's esophagus. Key words: gastroesophageal reflux disease, Barrett's esophagus, fluorescent diagnosis, local fluorescent spectroscopy.
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Loss of heterozygosity in the BRCA1 and BRCA2 locus in breast cancer
Статья научная
One of the factors of variability of malignant neoplasms is the loss of heterozygosity (LOH). The biological meaning of LOH, in relation to carcinogenesis, is associated with the inactivation of heterozygous loci of pathogenetically significant genes. Thus, the aim of this work was to study BRCA1/2 LOH in breast tumors. Material and Methods. The study included 122 patients with stage IIAIIIC breast cancer. DNA was isolated from 122 biopsy samples of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). To assess the status of LOH, microarray analysis was performed on high-density DNA chips from Affymetrix CytoScanTM HD Array. To process the results of microchipping, we used the Chromosome Analysis Suite 3.3 program (Affymetrix, USA). Results. The loss of heterozygosity in the BRCA1 gene was found to be associated with response to NAC. It was shown that in 59 patients LOH in the BRCA1gene was associated with an objective response to treatment (p=0.005). The presence of LOH in the studied genes was associated with a favorable prognosis. The 5-year non-metastatic survival rates were 75 % and 100 % in patients with LOH in the BRCA1 and BRCA2 genes, respectively (log-rank test: p=0.003 and p=0.05, respectively). Conclusion. The phenomenon of LOH in the BRCA1/2 genes was shown to be associated with response to NACT. BRCA1/2. Further studies are needed to evaluate the frequency of BRCA1/2 LOH after NAC for choosing and changing treatment tactics.
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MIR-155 и MIR-223 как маркеры клинических особенностей течения хронического лимфолейкоза
Статья научная
Введение. Хронический лимфолейкоз (ХЛЛ) - заболевание, которое характеризуется высокой межиндивидуальной гетерогенностью как клинического течения, так и молекулярных паттернов экспрессии генов и регуляторных РНК, способных оказывать влияние на патологический процесс. Вовлеченность регуляторных miR-155 и miR-223 в патогенез ХЛЛ в целом известна, но информации о возможных колебаниях экспрессии miR-155 и miR-223 в зависимости от динамики развития патологического процесса и характеристик врачебного вмешательства недостаточно. Цель исследования - изучение уровня экспрессии miR-155 и miR-223 у больных ХЛЛ с разными биологическими, клиническими особенностями и характеристиками проводимой терапии в субстратах периферической крови: плазме, лимфоцитах, внеклеточных везикулах, а также в костном мозге. Материал и методы. При выполнении работы использовались образцы периферической крови и костного мозга 38 пациентов с диагнозом ХЛЛ из Городского гематологического центра ГБУЗ Новосибирской области «Городская клиническая больница № 2» с 2016 по 2017 г. Оценка уровня экспрессии miR-155 и miR-223 проводилась методом ОТ-ПЦР в реальном времени по принципу TaqMan. Оценку значимости различий групп проводили с помощью непараметрического критерия Манна-Уитни либо непараметрического критерия Краскела-Уоллиса с последующим попарным сравнением с помощью критерия Манна-Уитни.
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Menopausal syndrome and its correction for oncogynecological patients
Статья научная
The review presents the problem of climacteric syndrome in reproductive-aged oncogynecological patients after antitumor treatment. A subject about correction of climacteric syndrome using substitutive hormonotherapy and non-hormonal methods (phytotherapy, phytohormones, homeopathy, vitamintherapy, behavior therapy and physical factors) was opened.
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Minimal invasive fertility sparing treatment of cervical cancer
Статья научная
This paper gives an overview of in particular surgical techniques that allow young women with cervical cancer to retain fertility.
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Статья научная
Activating mutations of egfr are associated with sensitivity of non-small cell lung cancer (NSCLC) to tyrosine kinase inhibitors (TKI). Liquid biopsy using circulating cell-free tumor DNA (cfDNA) is proposed in cases when formalin fixed paraffin embedded (FFPE) tumor tissue is not available and for monitoring of egfr status. In the study we evaluated new qPCR assay for egfr mutations in plasma cfDNA. Sensitivity of the assay was 1 % of the mutant allele for L858R, L861Q, S768I mutations and deletions in exon 19, and 5 % of the mutant allele for G719X or T790M mutations Before surgery, mutation was detected in plasma of 4 out of 7 patients (57 %) with mutant egfr in FFPE tumor tissue. Mutations found in cfDNA completely matched those found in tumor tissue in 2 cases. In one case with G719X and S768I mutations in FFPE tissue, only S768I was found in cfDNA. In another case, T790M was detected in plasma in addition to L858R that was present in tumor tissue. No egfr mutations were detected in plasma DNA from 12 healthy volunteers and 13 cases of NSCLC with wt egfr suggesting 100 % specificity of the assay. Liquid biopsy detected egfr mutations in cfDNA in 8 of 16 cases of NSCLC with mutant egfr being under therapy with TKI. Among them, 7 cases had mutations in liquid biopsy that matched those in tumor tissue and another case had T790M in addition to L858R. In 3 cases increased mutant allele frequency was detected 212 months before clinical progression.
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Morphological heterogeneity of intratumoral macrophages in prostate tumors
Статья научная
Background. Prostate cancer (PCa) is the most common human cancer worldwide. in the progression of prostate cancer, the total number of macrophages in the tumor tissue is associated with poor prognosis and increased risk of metastasis. However, the heterogeneity of intratumoral macrophages at various stages of PCa development, and the role of tumor-associated macrophages (TAMs) have been insufficiently investigated. The aim of the study was to analyze the morphological features, size and number of TAMs in PCa tissue samples, and to reveal their correlation with clinical data of patients. Material and Methods. immunohistochemical analysis of 36 paraffin blocks of patients with PCa (pT2a-3bN0-1M0) was performed using antibodies to the scavenger receptor CD68. Results. Foamy CD68+ macrophages were found in the tumor tissue. The indicator "number of macrophages per total number of fields of view with macrophages" was the lowest in patients with a Gleason score of 6 (5.8) (11.0 - in patients with a Gleason score > 8). Macrophages formed larger clusters in patients with severe PCa. Small but not large macrophages were significantly more common in patients with lymph node metastases (48 vs 24 in the N0 group; p=0.14). The number of small macrophages (smaller than 100 pm2) increased in a series of patients with Gleason scores of 6, 7 and > 8 (24, 47.5, 72, respectively, p=0.052). Conclusion. As the tumor process progressed and the risk of biochemical recurrence increased, there was a trend towards an increase in the total area of large, foamy TAMs, presumably rich in lipids, as well as wider distribution of small macrophages with a tendency to form clusters. We hypothesize that foamy macrophages are involved in the further recruitment of small TAMs, subsequently leading to metastasis and tumor progression.
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Статья научная
Objective. In accordance with clinical guidelines, neoadjuvant chemoradiotherapy (nCRT) is recommended as a beneficial option for treatment of thoracic esophageal squamous cell carcinoma (TESCC). However, some studies did not demonstrate potential benefits of nCRT. In this paper we compared treatment outcomes of surgery alone with preoperative CRT followed by surgery. Material and Methods Group 1 (n=147) consisted of patients who underwent surgery alone. Group 2 (n=3,337) was formed in the framework of the present systematic review and meta-analysis (15 publications captured 20 separate subgroups for analysis). Patients of group 2 received nCRT followed by esophagectomy. Overall survival (OS) and median OS were estimated.
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New mutation of the TP53 gene associated with the hereditary breast cancer in a young tuvinian woman
Статья научная
Background. The identification of the ethnospecific mutations associated with hereditary breast cancer remains challenging. Next generation sequencing (NGS) technology fully enables the compilation of germline variants associated with the risk for inherited diseases. Despite the success of the NGS, up to 20 % of molecular tests report genetic variant of unknown significance (VUS) or novel variants that have never been previously described and their clinical significances are unknown. To obtain extended information about the variants of the unknown significance, it is necessary to use an alternative approach for the analysis of the NGS data. To obtain extended characteristic about the unknown significance variants, it is necessary to search for additional tools for the analysis of the NGS data. Material and Methods. We reclassified the mutation of the unknown significance using the ActiveDriveDB database that assessed the effect of mutations on sites of post-translational modifications, and the ProteinPaint tool that complemented the existing cancer genome portals and provided a comprehensive and intuitive view of cancer genomic data. Results. in this study, we report a 44-year-old Tuvinian woman with a family history of breast cancer. Based on the NGS data, mutational analysis revealed the presence of the LRG_321t1: c.80C>T heterozygous variant in exon 2, which led to the proline to leucine change at codon 27 of the protein. in the dbPubMed database, this mutation was determined as unknown significance due to data limitation. According to the data of the ActiveDriverDB tool, this mutation is located distally at the site of post-translational protein modification, which is responsible for binding to kinases that regulate genes of the cell cycle, etc. (ATM, CHEK2, CDK, MAPK). in accordance with ProteinPaint tool, the LRG_321t1: c.80C>T mutation is located in functionally specialized transactivation domains and codon of the TP53 gene, where the pathogenic mutation associated with Li-Fraumeni syndrome has been earlier described. Conclusion. This report is the first to describe a new variant in the TP53 gene (rs1555526933), which is likely to be associated with hereditary cancer-predisposing syndrome, including Li-Fraumeni syndrome, in a Tuvinian BC patient with young-onset and familial BC.
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Nivolumab monotherapy in metastatic colorectal cancer: current approaches to response evaluation
Статья научная
Aim of the study: a systematic analysis of the modern literature data on the nivolumab monotherapy efficacy in patients with metastatic colorectal cancer (mCRC). Material and Methods. The review summarizes the results of clinical studies of the nivolumab efficacy in patients with mCRC between 2012 and 2022. The current approaches to assessing the tumor response in patients treated with immune checkpoint inhibitors are considered, including response patterns and criteria. Results. Data analysis showed that the use of nivolumab in mCRC patients had significant clinical benefits. Nivolumab monotherapy was shown to improve survival in patients with high microsatellite instability (MSi) or deficiencies in mismatch repair (dMMR) that progressed during standard chemotherapy. Numerous clinical studies indicate the atypical response to nivolumab. Traditional response criteria, such as RECiST do not always adequately assess the therapeutic efficacy of nivolumab in patients with mCRC. conclusion. To improve the efficacy of mCRC treatment, standardized approaches based on the proposed specific criteria for response to immunotherapy, including immune related RECiST, immune RECiST, and immune-modified RECiST must be developed.
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Статья научная
Introduction. In the development of new methods of radiotherapy, studies of the biological effects of sparsely (photons, electrons) and densely (protons, ions) ionizing radiation are relevant. Reproducibility is a challenge in preclinical studies. Dosimetric phantoms of laboratory animals are an effective tool for dose assessment, facilitating standardization of tests conducted under different conditions. Existing phantoms often fail to address radiobiological issues like placing of biological samples or dosimetry detectors. A method for manufacturing dosimetric phantoms must be developed to accurately manufacturing products and modify their design in accordance with the task.
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OТО-IVM - метод сохранения фертильности пациенткам с опухолевым поражением яичников
Статья научная
Введение. Все большее число пациенток репродуктивного возраста сталкивается с онкологическим заболеванием и высоко заинтересованы в сохранении фертильности. Улучшаются показатели выживаемости онкологических пациентов. Совершенствуются методы репродуктивных технологий, позволяющие сохранить способность деторождения. Реабилитация с целью обеспечения удовлетворительного качества жизни приобретает новый смысл, а с развитием новых технологий изменяется и уровень возможной помощи. В настоящее время реабилитационные мероприятия для онкологических пациенток репродуктивного возраста, несомненно, должны включать все возможные меры по сохранению и восстановлению фертильности. Цель исследования - сохранение фертильности пациенток с опухолевым поражением яичников. Материал и методы. После овариоэктомии яичники транспортировали в лабораторию эмбриологии, где проводили извлечение ооцит-кумулюсных комплексов и их последующее дозревание методом OTO-IVM (Ovarian tissue oocyte in vitro maturation). Полученные зрелые ооциты (метафаза II) криоконсервировали методом витрификации или, при наличии партнера, оплодотворяли методом ИКСИ (интрацитоплазматической инъекции сперматозоида), эмбрионы культивировали до стадии бластоцисты и также криоконсервировали методом витрификации. Криоконсервированные ооциты и эмбрионы могут быть использованы после излечения онкологического заболевания в программах вспомогательных репродуктивных технологий.
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Статья научная
The mechanism of the relationship between pretumor changes in the bronchial respiratory epithelium and the risk of progression of non-small cell lung cancer (NSCLC) remains unclear. It has been suggested that the relationship between reactive changes in the bronchial mucosa and NSCLC progression may be caused by the functional status of monocytic-macrophage cells as important participants in inflammation, which determines both the risk of premalignant changes in the epithelium and malignant progression. The purpose of the study was to investigate the phenotypic profile of peripheral blood monocytes and macrophages induced from monocytes in vitro depending on the state of respiratory epithelium in NSCLC patients. Material and Methods. The study included 39 patients with newly diagnosed NSCLC. Based on the morphological examination of small bronchi taken at the distance of 3-5 cm from the tumor, patients were divided into the following groups depending on the type of pretumor changes: no pretumor changes (n=6), isolated basal cell hyperplasia (BCH) (n=13), combination of BCH and squamous metaplasia (SM) (n=3), combination of unchanged epithelium and focal BCH (n=17). The phenotypic features of peripheral blood monocytes and in vitro-induced macrophages were assessed before treatment using flow cytometry. Results. The state of the respiratory epithelium in NSCLC patients prior to the start of anticancer treatment was associated with the phenotypic features of peripheral blood monocytes, but not with the profile of macrophages induced from them. Distortion of the response of induced macrophages to the polarizing stimuli was observed in NSCLC patients: the cultured cells responded to both M1 and M2 inducers (LPS and IL-4, respectively) with a phenotype shift to M2, while the CD206 marker expression varied depending on the presence and type of pretumor changes. Conclusion. The phenotypic profile of peripheral blood monocytes was associated with the state of the respiratory epithelium in NSCLC patients before anti-tumor treatment, but not with the phenotypic features of induced macrophages.
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