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Laser induced autofluorescence of normal and metaplastic epithelium of esophagogastric transition at gastroesophageal reflux disease

Laser induced autofluorescence of normal and metaplastic epithelium of esophagogastric transition at gastroesophageal reflux disease

Dronova O.B., Tretyakov A.A., Mishchenko A.N., Bulgakova N.N.

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

Loss of heterozygosity in the BRCA1 and BRCA2 locus in breast cancer

Tsyganov Matvey M., Ibragimova Marina K., Pevzner Alina M., Litviakov Nikolay V.

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

MIR-155 и MIR-223 как маркеры клинических особенностей течения хронического лимфолейкоза

Перепечаева М.Л., Горева О.Б., Березина О.В., Поспелова Т.И., Гришанова А.Ю.

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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Memory of G.F. Ginsburg

Memory of G.F. Ginsburg

Персоналии

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Memory of academician RAMS A.F. Tsyb

Memory of academician RAMS A.F. Tsyb

Персоналии

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Menopausal syndrome and its correction for oncogynecological patients

Menopausal syndrome and its correction for oncogynecological patients

Molchanov S.V., Kolomiets L.A., Gridneva T.D.

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

Minimal invasive fertility sparing treatment of cervical cancer

Verheijen R.H.M.

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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Monitoring of EGFR mutations in the circulating tumor DNA from blood plasma of patients with non-small cell lung cancer

Monitoring of EGFR mutations in the circulating tumor DNA from blood plasma of patients with non-small cell lung cancer

Shamanin Vladimir A., Karpov Igor V., Gervas Polina A., Cherdyntseva Nadezhda V., Simolina Elena I., Kozlov Vadim V., Kovalenko S.P.

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

Morphological heterogeneity of intratumoral macrophages in prostate tumors

Danilko K.V., Enikeeva K.I., Kabirov I.R., Maksimova S.Y., Vishnyakov D.S., Kzhyshkowska J.G., Pavlov V.N.

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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Neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma: does everyone need it?

Neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma: does everyone need it?

Chichevatov D.A., Sinev E.N., Glukhov A.E., Seliverstova O.M.

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

New mutation of the TP53 gene associated with the hereditary breast cancer in a young tuvinian woman

Gervas Polina A., Molokov Aleksey Yu., Zarubin Aleksei A., Ponomareva Anastasia A., Babyshkina Nataliya N., Belyavskaya Valentina A., Pisareva Lubov F., Choynzonov Evgeny L., Cherdyntseva Nadezda V.

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

Nivolumab monotherapy in metastatic colorectal cancer: current approaches to response evaluation

Babyshkina N.N., Dronova T.A., Gervas P.A., Popova N.O., Dobrodeev A.Yu., Kostromitskiy D.N., Afanasyev S.G., Goldberg V.E., Cherdyntseva N.V.

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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Numerical simulation of radiotherapy beam interaction with soft tissues and pla plastic for 3D printing of dosimetric phantoms

Numerical simulation of radiotherapy beam interaction with soft tissues and pla plastic for 3D printing of dosimetric phantoms

Miloichikova I.A., Bulavskaya A.A., Polomoshnova D.A., Saburov V.O., Stuchebrov S.G.

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

OТО-IVM - метод сохранения фертильности пациенткам с опухолевым поражением яичников

Лавринович О.Е., Татищева Ю.А., Берлев И.В., Яковлева М.Г., Карицкий А.П., Калугина А.С.

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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PLA полиморфизм гена GP3A как фактор прогноза при раке почки

PLA полиморфизм гена GP3A как фактор прогноза при раке почки

Серегин А.В., Кашинцев К.Ю., Енгай В.А., Шустицкий Н.А., Серегин А.А.

Статья

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Phenotypic profile of monocyte-macrophage lineage cells as a function of respiratory epithelium status

Phenotypic profile of monocyte-macrophage lineage cells as a function of respiratory epithelium status

Fedorov A.A., Ermak N.A., Topolnitskiy E.B., Shefer N.A., Rodionov E.O., Pankova O.V., Cherdyntseva N.V., Stakheyeva M.N.

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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Predicting the site of distant metastases in breast cancer

Predicting the site of distant metastases in breast cancer

Grigoryeva E.S., Ivanyuk E.E., Choinzonov E.L., Cherdyntseva N.V.

Статья научная

Background. Distant organ tumor dissemination is a major cause of breast cancer-related deaths. Breast cancer can metastasize to several organs, and the most frequent metastatic sites include the bones, lungs and liver. There is a question what factors can influence the direction of spread of tumor cells to a particular organ. Material and Methods. We summarized the data available in the world literature on methods for prediction of the localization of distant metastases in breast cancer patients. Results. We divided the factors associated with the localization of distant metastases into two main groups: clinicopathological parameters of breast cancer patients and molecular features of tumor microenvironment and tumor cells (primary tumor and circulating tumor cells) or its derivates - exosomes. From our point of view, the most powerful clinicopathological factor predicting the distant metastasis site is a molecular subtype of primary tumor. We can conclude that luminal (HR+/HER2-) tumors are often characterized by single metastases and bones are the most common metastatic site, while TNBC and HER2-enriched tumors often metastasize to multiple sites, most commonly brain and liver. However, several authors did not reveal these associations in their studies. It likely indicates the existence of other factors that significantly affect the organotropism of metastasis. Numerous studies demonstrate the association of different molecules expressed on tumor cells with organotropic metastasis. However, these data are very fragmentary and rather contradictory. Conclusion. The found associations are common to all participants of metastatic cascade, but remains unclear which factors are essential and crucial in determining the direction of metastasis.

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Predictive and prognostic significance of loss of heterozygosity in ABC transporter genes in breast cancer

Predictive and prognostic significance of loss of heterozygosity in ABC transporter genes in breast cancer

Tsyganov M.M., Ibragimova M.K., Garbukov E.Yu., Bragina O.D., Zdereva E.A., Usynin E.A., Litvyakov N.V.

Статья научная

ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. Therefore, the aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and Methods. A total of 130 breast cancer patients were included in the study. Microarray analysis was performed on Affymetrix CytoScan™ HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. The frequency of LOH ranged from 6.9 % to 90 %. An association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. The presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p

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Predictors of local recurrence of renal cell cancer. Our experience

Predictors of local recurrence of renal cell cancer. Our experience

Gaas M.Y., Kaprin A.D., Vorobyev N.V., Kalpinsky A.S., Kozlov V.V., Inozemtsev R.O.

Статья научная

Risk factors for renal cell cancer (Rcc) recurrence, including its local form, include stage and high Fuhrman grading system score, regional lymph node involvement, microvascular invasion, tumor necrosis, positive surgical margin, and sarcomatoid or rhabdoid tumor differentiation. Objective. the study analyzes data from moscow Research oncological institute named by pa Herzen to determine the predictors of local recurrence of kidney cancer based on the data from surgically treated patients with local recurrent Rcc. material and methods. We analyzed retrospectively data from 87 patients who were divided into 2 groups: 1-st, patients with detected local recurrence of kidney cancer (n=43), and 2-nd, control group (n=44). the following predictors were evaluated: tumor size, tumor histotype, tumor stage, Fuhrman grading system, surgical margin status, tumor necrosis, sarcomatoid and rhabdoid changes, microvascular invasion, hemorrhage and invasion of collecting system components (css), renal capsule, and perirenal cellular tissue and primary treatment. Results. the risk of local recurrence was higher in the primary tumor, over 40 mm in diameter (oR=5.8, p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }

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Primary liver cancer in the Republic of Sakha (Yakutia)

Primary liver cancer in the Republic of Sakha (Yakutia)

Bugaeva T.T., Ivanov P.M., Alekseeva M.N., Odintsova I.N., Boyarkina A.P.

Статья научная

Territorial and ethnic features of the prevalence of primary liver cancer in the republic of Sakha have been studied. The republic has been shown to be a high-risk area for primary liver cancer, which is the 2-nd most common form of cancer in males and the 3-rd most common form of cancer in females among all digestive system malignancies. The standard liver cancer incidence rates are 5 times higher than the average incidence rates in Russia. Primary liver cancer is more oftern registered in the age group of 70 years and more. Incidence rates are mainly raised due to indigenous and rural populations. The liver cancer incidence rates show a tendency to stabilization all over the republic.

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