Experimental oncology最新文献

{"title":"CLINICAL SIGNIFICANCE OF BRCA1 GENE SEQUENCING AND ITS PROMOTER METHYLATION TESTING IN THE SEARCH STRATEGY FOR THERAPEUTIC TARGETS IN BREAST CANCER TREATMENT.","authors":"L Fishchuk,&nbsp;O Lobanova,&nbsp;Z Rossokha,&nbsp;V Cheshuk,&nbsp;R Vereshchako,&nbsp;Yu Vagyn,&nbsp;V Kashuba,&nbsp;V Vershyhora,&nbsp;O Popova,&nbsp;N Levkovich,&nbsp;O Zemlianska,&nbsp;O Ievseienkova,&nbsp;S Podolska,&nbsp;N Gorovenko","doi":"10.15407/exp-oncology.2023.02.161","DOIUrl":"10.15407/exp-oncology.2023.02.161","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is a great interest in the genetic testing of BRCA1 and BRCA2 due to the fact that for patients with breast cancer (BC) with pathogenic variants of these genes, the use of the PARP inhibitors could be also provided in addition to implemented treatment protocols. The aim of this study was to characterize the molecular genetic structure of the BRCA1 gene in BC patients without progenitor germline mutations taking into account the methylation state of the promoter region.</p><p><strong>Materials and methods: </strong>The study involved 210 patients with newly diagnosed BC. The most common germline pathogenic variants of the BRCA1 (185delAG, 5382insC, 4153delA, T300G) and BRCA2 (6174delT) genes were identified in the peripheral blood. A subgroup of 14 patients without progenitor pathological variants of the BRCA1 and BRCA2 genes and with a family history of cancer was randomly selected. For them, BRCA1 gene sequencing by Sanger and hypermethylation of the BRCA1 gene promoter region were analyzed.</p><p><strong>Results: </strong>The following frequencies of BRCA1 mutations were determined in the general group: 5382insC - 8.6%, 4153delA - 0.5%, T300G - 0.5%. The analysis of the BRCA1 gene by Sanger sequencing revealed 11 BRCA1 gene variants in 10 out of 14 BC patients. All of them, according to the currently available data, were defined as \"benign\" and not clinically relevant. The frequency of the detection of hypermethylation of the BRCA1 gene promoter region in the randomly selected group of patients was 14.3%.</p><p><strong>Conclusions: </strong>In BC patients, not only common mutations but also the methylation status of the BRCA1 gene promoter region in the peripheral blood should be determined. The whole-genome sequencing of the BRCA1 gene may be the last step in determining the genetic characteristics of BC patients carried out to optimize the treatment and improve survival thanks to the higher prevalence of the progenitor mutations and hypermethylation of the BRCA1 gene promoter.</p>","PeriodicalId":94318,"journal":{"name":"Experimental oncology","volume":"45 2","pages":"161-169"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF MARKERS OF BONE TISSUE REMODELING IN BREAST CANCER AND PROSTATE CANCER CELLS IN VITRO","authors":"N Lukianova, T Zadvornyi, E Kashuba, T Borikun, О Mushii, F Chekhun","doi":"10.32471/exp-oncology.2312-8852.vol-44-no-1.17354","DOIUrl":"https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-1.17354","url":null,"abstract":"The aim of the study was to compare the expression of markers of bone remodeling in vitro in breast cancer (BCa) cells and prostate cancer (PCa) cells varying in their malignancy phenotype. Materials and Methods: The study was performed on human BCa cells (MCF-7 and MDA-MB-231 lines) and PCa cells (LNCaP and DU-145 lines). Expression levels of bone tissue remodeling proteins (osteopontin (OPN), osteonectin (ON) and bone morphogenetic protein 7 (BMP-7) were determined immunocytochemically. The mRNA levels of bone tissue remodeling proteins OPN (SPP1), ON (SPARC), BMP-7 (BMP7)) and miRNA-10b, -27a, -29b, -145, -146a were assessed by quantitative reverse transcription polymerase chain reaction. To search for miRNAs involved in the regulation of target genes, miRNet v. 2.0 resource was used. Results: We have shown that highly malignant MDA-MB-231 cells are characterized by significantly higher expression of OPN and ON on the background of decreased SPARC and BMP7 mRNA expression. In highly malignant DU-145 cells, ON and SPP1, SPARC, and BMP7 mRNA expression was significantly higher compared with low malignant LNCaP cells. MDA-MB-231 line was characterized by significantly higher expression of miRNA-10b, -27a, -29b, -145 and -146a. In DU-145 cells, significantly lower levels of expression of miRNAs-27a and -145 against the background of increasing levels of miRNAs-29b and -146a were recorded. Conclusion: High malignancy phenotype of the BCa and PCa cells is characterized by high levels of expression of bone remodeling proteins, which may be caused by impaired regulation of their expression at the epigenetic level.","PeriodicalId":94318,"journal":{"name":"Experimental oncology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135996321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVALUATION OF THE EFFICIENCY OF ALPHA-LIPOIC ACID AND IPIDACRINE HYDROCHLORIDE FOR THE PREVENTION OF PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY ACCORDING TO THE TOTAL NEUROPATHY SCORE","authors":"I S Holotiuk, A Ye Kryzhanivska, S I Holotiuk, S V Maliborska, V V Holotiuk","doi":"10.32471/exp-oncology.2312-8852.vol-44-no-1.17257","DOIUrl":"https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-1.17257","url":null,"abstract":"To evaluate the efficacy of combination of alpha-lipoic acid and acetylcholinesterase inhibitor (ipidacrine hydrochloride) to prevent the development and improve the course of paclitaxel-induced peripheral neuropathy (PIPN) in patients with breast cancer according to the Total Neuropathy Score.32 patients with breast cancer T1-4N0-3M0 received six cycles of polychemotherapy according to the AT scheme (paclitaxel, doxorubicin) or ET scheme (paclitaxel, epirubicin). Patients were randomized into two groups - without (group I) or with (group II) medication for prevention of neuropathy. A comprehensive neurological examination of patients was performed according to all ten parameters of the Total Neuropathy Score before chemotherapy, and after third and sixth cycles of chemotherapy. Each parameter was evaluated from 0 (no deficit) to 4 (no function/the most severe deficit). The scores obtained from the scale were summarized to obtain a total score from 0 to 40.The use of alpha-lipoic acid in combination with an acetylcholinesterase inhibitor (ipidacrine hydrochloride) significantly reduces the symptoms and severity of PIPN. The manifestations of PIPN in patients of the control group were significantly more severe compared to the group in which the study drugs were used. The average severity of neuropathy after 3 and 6 cycles was 1.75 and 2.62 in group I, and 1.12 and 1.62 - in group II, respectively (improvement by 15.75% (p < 0.05) and 25.00% (p < 0.001) after 3 and 6 cycles).Proposed combination of alpha-lipoic acid and ipidacrine hydrochloride led to a statistically significant reduction in the severity of PIPN, and thus to improvement of the functional capacity and quality of life of patients.","PeriodicalId":94318,"journal":{"name":"Experimental oncology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135996971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAPTOR PROTEIN Ruk/CIN85REGULATES REDOX BALANCE IN 4T1MOUSE BREAST CANCER CELLS EXPOSED TO PLASMIN(OGEN)","authors":"I R Horak, N V Latyshko, O O Hudkova, K O Tokarchuk, T O Kishko, O I Yusova, L B Drobot, A A Tykhomyrov","doi":"10.32471/exp-oncology.2312-8852.vol-44-no-1.17241","DOIUrl":"https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-1.17241","url":null,"abstract":"Cell surface plasmin is involved in tumor growth and metastatic dissemination by regulating cancer cells adhesion, migration and invasion. Plasmin-induced cell detachment is accompanied by an increased rate of reactive oxygen species (ROS) generation and cell death. However, cancer cells acquire the ability to develop adaptive mechanisms to resist ROS-mediated apoptosis.To establish the role of adaptor protein Ruk/CIN85 in the control of viability and redox balance in breast adenocarcinoma cells exposed to plasmin(ogen).Mouse 4T1 cells with the stable overexpression of adaptor protein Ruk/CIN85 (RukUp subline) and corresponding control (Mock subline) were treated with Glu-plasminogen (1-100 nM). Plasminogen to plasmin conversion was monitored spectrophotometrically by cleavage of the specific chromogenic substrate S2251. Specific uPA inhibitor BC11 was used to verify the uPA-mediated mechanism of plasminogen pericellular activation by 4T1 cells. Cell survival rate was assessed by MTT-test and cell proliferation was estimated by colony formation assay. Enzymatic activities of catalase, glutathione peroxidase, superoxide dismutase, as well as hydrogen peroxide (H2O2) levels were measured by spectrophotomertric and fluorometric assays. The intracellular ROS generation was monitored by flow cytometry using H2DCF-DA fluorescent probe.Plasminogen was shown to be converted into an active proteinase plasmin on the surface of carcinoma cells in uPA-dependent manner. Plasmin(ogen) suppressed proliferation and affected survival of both studied 4T1 sublines. However, RukUp cells displayed higher resistance to plasmin(ogen)-induced cytotoxicity than Mock cells. Plasmin(ogen) promoted significant elevation in ROS generation rate in cells with the basal level of Ruk/CIN85 expression. In contrast, RukUp cells appear to be more effective in counteracting prooxidant changes due to the activation of some enzymes of the glutathione system, in particular glutathione peroxidase, and a concomitant decrease of H2O2 accumulation.Adaptor protein Ruk/CIN85 is involved in the regulation of redox homeostasis in cancer cells to maintain levels of ROS, thus promoting redox adaptation in cancer cells exposed to plasmin(ogen). Thus, Ruk/CIN85 may represent one of the relevant targets in order to diminish the resistance of cancer cells to ROS-mediated apoptosis.","PeriodicalId":94318,"journal":{"name":"Experimental oncology","volume":"123 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135996973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A LONG-TERM 10G-HYPERGRAVITY EXPOSURE PROMOTES CELL-CELL CONTACTS AND REDUCES ADHESIVENESS TO A SUBSTRATE, MIGRATION, AND INVASIVENESS OF MCF-7HUMAN BREAST CANCER CELLS","authors":"S Kannan, H Shailesh, H Mohamed, N Souchelnytskyi, S Souchelnytskyi","doi":"10.32471/exp-oncology.2312-8852.vol-44-no-1.17270","DOIUrl":"https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-1.17270","url":null,"abstract":"G-force is a fundamental force controlling human cells. Cancer is one of the 4 major health challenges in the Space missions. Cancer in Space project evaluates the reaction of human cancer cells to the conditions of the space flights, including an exposure to high g-forces.Explore an impact of 10 g force on the oncogenic properties of human breast adenocarcinoma cells MCF-7.Cells were exposed to 10 g force for 10 days, as part of a 6-week simulation of conditions of a space flight. Then the cells were cultured for one week under normal culture conditions, before performing tests. Cell proliferation, cell viability, cell-cell contact inhibition, migration, and invasiveness were measured. Immunoblotting was used to evaluate expression of proteins.Proliferation, cell-cell interaction and formation of 3D structures, migration, and invasiveness of cells exposed to 10 g were compared to parental cells cultured at 1 g condition. 10 g exposed cells showed a higher propensity for cell-cell contact inhibitions and lower for 3-dimensional growth in dense culture. This correlated with the decrease of proliferation in a dense culture as compared to the parental cells. The decrease of migration, adherence to a surface, and invasiveness was observed for cells subjected to the hypergravity, as compared to the parental MCF-7 cells. Enhanced expression of E-cadherin and phosphorylated pY576-FAK were observed in 10 g exposed cells but no impact on the expression of Erk, pErk, FAK and p53 was detected.The prolonged exposure of MCF-7 cells to 10 g force targets cell-cell and cell-substrate interactions.","PeriodicalId":94318,"journal":{"name":"Experimental oncology","volume":"118 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135996972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}