Experimental oncology最新文献

Tumors of the right uterine appendages cannot always be distinguished from mucous neoplasms of the appendix (MA) at the preoperative stage. According to the literature, MA is traditionally considered more common in women than in men at the age of 50 years, with a ratio of 4:1. We have identified 2 cases of surgical treatment of MA in gynecological practice, one of mucinous cystadenoma and the other of mucinous cystadenocarcinoma. We present the visual intraoperative assessment of the appendix condition in cystadenoma and cystadenocarcinoma, clinical manifestations, diagnostic discrepancies, and operative tactics. The literature on the detection of appendicular mucocele that mimics ovarian tumor formations in women has been reviewed. The features of diagnostics and possible diagnostic errors were summarized. Diagnostic laparoscopy, visual and operative clinical experience of the surgeon, and cytological and histological examinations of intra- and postoperative results allow for an adequate treatment. It is advisable that the stages and course of appendectomy be reviewed by operating gynecologists and, if necessary, general surgeons.

Background: Flavonoids, naturally occurring compounds found in plant-based products, are being investigated as potential non-invasive treatments due to their ability to inhibit cell growth, induce apoptosis, and prevent cell migration.

Aim: This study aims to investigate the effects of homoeriodictyol, a member of the flavanone group, both alone and in combination with docetaxel on the survival, apoptosis, migration, and proliferation of prostate cancer cells.

Materials and methods: Androgen-resistant prostate cancer PC3 cells were treated with various concentrations of homoeriodictyol, docetaxel, or a combination of both for 72 h. The treatment effects on cell survival, migration, apoptosis, and gene expression were evaluated using the MTT test, wound healing assay, Hoechst staining, and realtime PCR.

Results: Homoeriodictyol induced apoptosis in PC3 cells in a concentration-dependent manner, with a more potent effect in combination with docetaxel. Apoptosis occurred through both intrinsic and extrinsic caspase pathways, leading to the upregulation of CASP3, CASP8, TP53, BAX, and CYCS, and downregulation of BCL2 mRNA expression. Homoeriodictyol also exhibited antimigratory effects via upregulating CDH1, while decreasing CDH2 expression levels. It suppressed epithelial-mesenchymal transition by downregulating the expression of TWIST, SNAIL, and ZEB1, which correlated with the observed antimigratory effects in wound healing assays.

Conclusion: Homoeriodictyol exerted potent effects and inhibited prostate cancer cell proliferation and migration, especially when used in combination with docetaxel.

Background: Disorders of the L-arginine-citrulline cycle affect the functioning of the cardiovascular system. Cancerinduced augmentation of arginase activity stimulates the biotransformation of L-arginine to form polyamines, which causes NO deficiency and increases the risk of endothelial dysfunction in the category of high-risk patients for developing cytostatic-induced cardiotoxicity. The aim was to investigate features of L-arginine-citrulline cycle functioning in patients with multiple myeloma (MM) and concomitant coronary artery disease (CAD) during chemotherapy (CT).

Materials and methods: 42 patients with MM progression were examined and divided into 2 groups: group І (n = 20) - patients without CAD and group II (n = 22) - patients with CAD. The concentrations of L-arginine and citrulline and the activity of arginase in the blood serum of the patients were measured before and after the 1st and 5th courses of chemotherapy.

Results: Before chemotherapy, in patients of both groups, the blood serum level of L-arginine decreased, while the activity of arginase and the level of citrulline increased compared to healthy individuals. In patients of group II, the level of citrulline was higher than in patients of group I. After the 5th course of chemotherapy, L-arginine content in patients of both groups increased and citrulline levels decreased compared to the initial examination.

Conclusions: The progression of MM was accompanied by a decrease in the blood serum content of L-arginine along with an increase in the arginase activity in the blood serum compared to practically healthy individuals. An increase in the cumulative dose of cytostatics during CT in the MM patients with concomitant CAD led to a decrease in the content of L-arginine in the blood serum with a simultaneous increase in the content of citrulline compared to corresponding levels in MM patients without concomitant CAD.

Background: The ability to reorganize metabolic processes is one of the key properties of malignant cells necessary to ensure high energy needs, survival, proliferation, metastasis, and resistance to anticancer drugs. Lactic acid bacteria, in particular Bifidobacteria, are important elements of the tumor microenvironment in breast cancer (BC) and, as active lactate producers, can influence the metabolic phenotype of malignant cells.

Aim: To study the effect of B. animalis on some components of glucose metabolism pathways and the expression of proteins associated with this process in human BC cells of different molecular subtypes.

Materials and methods: The study was performed on human BC cells of the T-47D, MCF-7 (luminal subtype), and MDA-MB-231 (basal subtype) lines and live culture of Bifidobacterium animalis subsp. lactis (B. animalis). A colorimetric enzymatic technique, flow cytometry, immunocytochemical analysis, and cell viability trypan blue exclusion assay were used in the study.

Results: Co-cultivation of BC cells with B. animalis resulted in a significant (p < 0.05) increase in the glucose consumption rate by 1.2-4.7 times, lactate production by 15-115%, and LDH activity by 15-160% in BC cells compared to control cells. The most pronounced changes were observed in BC cells of the luminal subtype where they were accompanied by an increase in the expression of the GLUT1 glucose transporter by 30-80% compared to control cells. Also, after co-cultivation with B. animalis, we detected an increased expression of the STAT6 transcription factor in BC cells of all three lines.

Conclusions: Co-cultivation of BC cells with B. animalis is accompanied by an increase in glycolysis. B. animalis affected not only the biochemical components of the glucose metabolism pathway but also the expression levels of STAT6, GLUT1, and insulin receptor.

Among 11,152 patients treated for complicated portal hypertension (PH) in the Kyiv Emergency Hospital in 2000- 2023, 394 (3.5%) had sinistral portal hypertension (SPH), the etiological factor of which in one patient (0.25% of SPH cases, 0.009% of all PH cases) was diffuse large B-cell lymphoma (DLBCL). We provide an example of successful surgical treatment of a patient with DLBCL that was complicated by the development of SPH with bleeding from varicose veins of the stomach. A peculiarity and difference between SPH and other forms of PH is not only the preserved patency of the portal vein and the normal gradient of portal pressure but also the preserved liver function.

Background: Uterine sarcoma (US) is a rare type of tumor characterized by aggressive clinical behavior and high recurrence rate. Its histopathological heterogeneity has led to a lack of consensus regarding risk factors that could guide the selection of optimal treatment strategies for this pathology.

Aim: To investigate the factors influencing treatment outcomes of US.

Materials and methods: We conducted a retrospective analysis of the treatment outcomes of 107 women diagnosed with stage I-II US from 2010 to 2023. The follow-up period ranged from 1.0 to 156.0 months. Kaplan - Meier survival curves were used for the analysis of overall survival (OS) and recurrence-free survival (RFS) rates. The correlation between the studied parameters was analyzed including relative risk (odds ratio, OR) and correlation coefficient.

Results: The assessment of OR allowed us to identify the following prognostic factors with a negative impact on the 5-year OS and RFS of patients with US: differentiation grade G3, necrotic areas in tumor tissue, lymphovascular invasion, high mitotic activity (11 or more mitoses per 10 HPF), nuclear atypia 4+, negative ER and PR statuses, and high Ki-67 expression.

Conclusions: Survival of patients with US depends on tumor grade, necrosis, and lymphovascular invasion of tumor tissue; mitotic activity and nuclear atypia; ER and PR statuses; and the level of Ki67 expression.

Background: The coronavirus infection caused by SARS-Cov-2 virus, in addition to the development of severe acute respiratory syndrome, is responsible for the development of a multiple organ dysfunction syndrome. An important aspect is its relationship with cancer. The data from clinical and experimental studies are contradictory. Thus, further studies are needed to elaborate on the potential effects of SARS-Cov-2 on cancer cells.

Aim: To study the effect of SARS-Cov-2 spike protein (SP) on the survival, phenotype, and sensitivity to radiation-induced apoptosis of breast cancer (BC) cell lines of different molecular subtype (MDA-MB-231 and MCF-7).

Materials and methods: The effects of SARS-Cov-2 SP on MDA-MB-231 and MCF-7 cells were assessed using the cell proliferation assay and flow cytometry (Ki-67, CD44, CD133, CD105, CD90, CD10, CD5, CD19, and p53). The sensitivity to radiationinduced apoptosis was evaluated by 7-amino-actinomycin D and propidium iodide staining.

Results: We did not find any significant short-term effect of SP on the proliferative activity of both studied cell lines. The phenotype of MDA-MB-231 cells cultured with SP changed toward a decrease in CD105+CD90+ and CD105+CD90- subpopulations (p < 0.0001). The p53 expression increased both in SP-treated MDA-MB-231 and MCF-7 cells. The sensitivity of SP-treated MDA-MB-231 and MCF-7 cells to radiation-induced apoptosis, although insignificantly, increased. Apoptosis in irradiated MDA-MB-231 cells was accompanied by a two-fold increase in the fluorescence intensity of p53 in SP-treated MDA-MB-231 cells. In both irradiated cultures, a significant increase in the percent of cells in S-phase after SP treatment was observed compared to SP-untreated cells.

Conclusion: Since most vaccines are based on SP expression, the obtained data might have a certain significance in the study of the effect of anti-SARS-Cov-2 vaccination on tumor growth and the sensitivity of cancer cells to cytoreduction therapies.

Cystectomy in Metastatic Bladder Cancer: Feasibility, Safety and Outcomes Hrechko B, Voylenko O, Pikul M, Vitruk U, Stakhovsky O, Kononenko O, Semko S, Koshel D, Tymoshenko A, Buyvol O, Stakhovsky E. Exp Oncol. 2024;46(4):345-350 DOI: https://doi.org/10.15407/exp-oncology.2024.04.345.

Background: In oncology, drug-drug interactions (DDIs) are particularly relevant due to the complex medication regimens of cancer patients. These patients often require multiple drugs to manage both their disease and treatment-related side effects. Evaluating potential DDIs via the inhibition of CYP enzymes is crucial in drug discovery. This study aimed to assess the effect of propoxazepam on CYP2C8 activity in vitro by amodiaquine N-deethylation in human liver microsomes and to predict the likelihood of DDI through CYP activity reduction.

Materials and methods: Amodiaquine Ndeethylation was used as a marker of CYP2C8 activity. The positive controls included montelukast (1 μM) for rever sible inhibition and gemfibrozil O-glucuronide (40 μM) for metabolism-dependent inhibition. Propoxazepam was tested in both reversible and metabolism-dependent inhibition conditions being added with the substrate or pre-incubated with microsomes and NADPH, respectively. The metabolite formation was quantified by LC-MS/MS in a multiple reaction monitoring mode using the electrospray ionization technique.

Results: Propoxazepam inhibited CYP2C8 activity in a concentration-dependent manner, with IC50 values of 20.5 ± 2.2 μM for reversible inhibition and 23.1 ± 3.2 μM for metabolism-dependent inhibition. Positive controls montelukast and gemfibrozil O-glucuronide showed expected inhibition (4.4% and 12.2% of control, respectively). Propoxazepam showed low binding to microsomal protein under the experimental conditions.

Conclusion: Based on the indicators used (Ki, IC50, IC50 shift, and [I]/Ki ratios), propoxazepam is not expected to be a significant CYP2C8 inhibitor in vitro.

Background: miRNAs have emerged as promising biomarkers for breast cancer, particularly in predicting treatment response and prognosis. Their ability to regulate gene expression and their presence in various bodily fluids make them valuable tools for personalized medicine.

Materials and methods: The study was based on a retrospective analysis of the results of the examination, treatment, and survival of 94 patients with stage II-III triple-negative breast cancer (TNBC) who underwent treatment at the Kyiv City Clinical Oncology Center during 2013-2017. miRNA expressions in blood serum were estimated using the real-time RT-PCR.

Results: The elevated levels of miR-21, -155, -199a, and -200b (p < 0.05) were linked to metastasis to regional lymph nodes, while miR-373 and -126 expression levels were associated with the tumor stage (r = 0.55 and 0.57, respectively, p < 0.05). The higher serum levels of miR-21 (> 5.4, p < 0.05), -125b (> 6.0, p < 0.05) and the lower miR-205 levels (< 2.0, p < 0.05) were associated with the poorer response to line I and II neoadjuvant chemotherapy. The serum levels of miR-21, -125b, -126, -199a, -200b, -205, and -373 were found to correlate with the overall and recurrence-free survivals in TNBC patients.

Conclusions: These findings suggest that miRNA-based biomarkers may have the potential as prognostic and predictive tools in TNBC, aiding in personalized treatment strategies.