Experimental oncology最新文献

Background: Effective prediction of the course of prostate cancer (PCa) and the stratification of treatment tactics largely depend on the use of prognostic markers that reflect the molecular and biological features of tumors. In view of the important role of matricellular proteins in the modulation of the growing tumor and metastasis of the hormone-dependent neoplasms, the aim of the work was to study the expression of osteopontin (OPN) at the protein and mRNA levels in the PCa tissue in order to assess the significance of this protein for predicting the aggressiveness of PCa.

Materials and methods: The work is based on the analysis of the results of the examination and treatment of 83 patients with PCa of stages II-IV. The study of OPN expression at the level of mRNA and protein in the PCa tissue was carried out using methods of the real time polymerase chain reaction and immunohistochemistry, respectively.

Results: The OPN expression in the PCa tissue was 1.6 times (p < 0.05) higher in patients with regional lymph node metastases compared to patients without metastases. In patients with a Gleason score of < 7, the OPN expression in the tumor tissue was 1.4 times lower (p < 0.05) than in patients with poorly differentiated PCa. In patients with a high risk of tumor progression, the OPN expression level was 1.4 and 2.1 times higher (p < 0.05) compared to patients with a moderate and low risk of PCa progression. The patients with a high OPN expression level in the PCa tissue had significantly decreased 2-year recurrence-free survival rate (by 25%).

Conclusions: The obtained results indicate the expediency of using OPN expression indicators in the tumor tissue to predict the PCa aggressiveness and assess the risk of its recurrence.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults. The improvement of the efficacy of GBM treatment is an urgent problem encouraging the development of novel therapeutic strategies, in particular, immunotherapeutic modalities. With more understanding of the intimate interrelationships between the immune system and the mechanisms involved in cancer origin and progression, the skepticism related to the relevance of the immunotherapeutic approaches in the treatment of brain tumors is gradually decreasing. The review discloses the modern concepts on the association between CNS and the immune system. For a long time, CNS was considered as the immunoprivileged site that prevents the effects of immunotherapy in the treatment of brain tumors. Nowadays, these views are reconsidered, which opens the way to the use of immunotherapeutic approaches in GBM treatment. The results of the recent clinical trials on immunotherapy as a supplement to the conventional GBM treatment are considered. Vaccines based on the dendritic cell (DC) technology are regarded as the most promising for this purpose. The preliminary results of the Ukrainian clinical study are also presented and discussed. The results of the international clinical trials as well as our own experience give evidence of the relevance for using DC vaccines in the complex treatment of GBM, which is supported by the increased survival of patients and the safety of vaccine application. It is of high importance that GBM patients with the most unfavorable prognosis can benefit from DC vaccines as a component of the complex treatment. The prospects for immunotherapy in neurooncology are discussed.

Aim: To evaluate the effectiveness of applying negative pressure bandages (VAC bandage) in patients with malignant skin tumors after closing defects with free skin grafts and to compare it with fixation of skin grafts by the ordinary ointment bandages.

Materials and methods: 61 patients with malignant skin tumors who underwent surgical treatment at the National Cancer Institute from 2019 to 2023 were included in the study. For the wound defects closure, the split skin grafts were applied in all patients. At the time of surgery, after closing a wound defect by a split skin graft, a negative pressure dressing (VAC bandage) was applied in 41 patients for 7 days (group 1). In 20 patients, a transplanted skin graft was fixed after surgery by an ordinary ointment pressure bandage (group 2). The immediate results were evaluated one week after surgery.

Results: Complete engraftment of the flap in group 1 was observed in 53.7 ± 7.8% cases, in group 2 this result was achieved in 5.0 ± 4.8% patients (p = 0.002). The complete graft necrosis occurred in 1 case in group 1 vs. 2 cases in group 2 (p = 0.496).

Conclusion: The results of the engraftment in postoperative wounds were significantly better in the VAC-bandage group in terms of the number of the complete engraftments compared to the conventional pressure ointment bandage group.

Background: The typical chronic lymphocytic leukemia (CLL) immunophenotype is vital for diagnosis, but the expression of some antigens varies and has prognostic value. There are data that reduced CD20 expression is associated with NOTCH1 and SF3B1 gene mutations.

Aim: To determine a high-risk group of CLL patients for prediction of unfavorable NOTCH1 and SF3B1 gene mutations based on immunophenotyping of leukemic cells.

Materials and methods: Flow cytometric and molecular-genetic analysis (mutations of NOTCH1, SF3B1, and TP53 genes using the polymerase chain reaction followed by direct sequencing) was performed in a group of 86 previously untreated CLL patients.

Results: The immunophenotype of leukemic cells of all examined patients met the criteria of CLL diagnosis. NOTCH1 gene mutations were found in 21 patients (24.4%), and SF3B1 gene mutations - in 7 patients (8.1%). There were no TP53 gene mutations among the examined patients. A decreased number of CD20+CD5+ cells and a downward trend in the relative index of mean fluorescence intensity (iMFI) of CD20+ cells were found in patients with NOTCH1 and SF3B1 gene mutations. Based on the iMFI level (higher and/or lower than 3.0) and the number of CD20+CD5+ cells among all B-cells (higher and/or lower than 50%), we distinguished CLL cases with low and relatively high levels of CD20 antigen expression. Using ROC analysis and the parameter of low CD20 antigen expression, we could predict the presence of NOTCH1 and SF3B1 gene mutations in 73.3 ± 0.06% of patients (p = 0.001). The risk of NOTCH1 and SF3B1 gene mutations in cases with low CD20 antigen expression was 6.96 (95% CI = 2.53-19.18; p = 0.0001). The revealed regularities were statistically significant for patients in whom the diagnosis was established in all Binet - Rai stages except A0-AI.

Conclusion: Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.

Breast cancer (BC) remains the most prevalent tumor and the leading cause of death among women worldwide, despite the advancements in diagnosis and new treatments. A significant challenge in BC treatment is the acquired or de novo resistance of tumors to systemic therapy. To overcome this obstacle, personalized treatment is needed, with a focus on finding biomarkers capable of predicting the response to therapy. MicroRNAs (miRNAs) have emerged as potential markers due to their diverse clinical applications.

Aim: To examine the potential prognostic significance of miR-125b-2, -155, -221, and -320a expression in the tumor cells of individuals with hormone-dependent BC before undergoing neoadjuvant hormonal therapy.

Materials and methods: The study is based on a retrospective analysis of the treatment outcome of 56 patients with stage II-III locally disseminated hormone-dependent BC. The real-time quantitative reverse transcription polymerase chain reaction was performed on the biopsy material to assess the expression of miR-125b-2, -155, and -221 before neoadjuvant hormonal therapy with aromatase inhibi- tor letrozole to predict clinical response.

Results: Most HER2/neu+ BC patients had low levels of miR-155 and miR-221 expression in tumor biopsy specimens. Tumors that responded well to letrozole exhibited lower levels of miR-125b-2 and miR-221 compared to non-responsive tumors.

Conclusions: miR-125b-2, -155, and -221 expres- sion can predict resistance to the letrozole treatment of BC.

The widespread introduction of nuclear technologies in industry, medicine, science, etc. increases the number of professionals subjected to additional radiation exposure. Moreover, the problem of occupational cancer is the most complicated in occupational pathology due to the multifactorial nature of the etiology of this disease. The radiation accidents in Chornobyl and Fukushima-1 showed that nuclear reactors cannot guarantee absolutely safe operation. At present, the threat of nuclear terrorism is increasing. Occupational radiation exposure and its consequences are also of great concern worldwide. Based on the literature data and our own studies on the effects of various types of radiation exposure, especially stochastic effects of radiation, it seems reasonable to develop a scientific basis for the optimization of radiation protection of various categories of population, first of all, medical personnel and patients. The complex assessment of radiation risks and reconstruction of the total ionizing radiation dose from all types of irradiation will allow optimizing radiation protection of the population and reducing carcinogenic risk..

Background: The intermittent Pringle maneuver remains the major technique for controlling hemorrhage during liver surgery. Nevertheless, this procedure involves a risk of triggering a cascade of pathological changes resulting in the ischemia-reperfusion injury (I/R) effect. The pharmacological prevention of this I/R injury represents a promising approach. The aim of the study was to compare the effects of pharmacological preconditioning with sevoflurane and propofol-based intravenous anesthesia on the postoperative function of the liver as the primary end-point.

Materials and methods: A prospective cohort study includes the analysis of the data of 73 patients who underwent liver surgery. In the study group (n = 41), preconditioning with sevoflurane inhalation was provided 30 minutes prior to liver resection. In the control group (n = 32), sevoflurane preconditioning was not provided. The primary endpoints were blood lactate concentration shortly after the surgery and one day later; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities on postoperative Days 1, 3, and 5 as markers of hepatocyte damage.

Results: On postoperative Day 1, in patients of the study group, lactate decreased to preoperative levels, while in the control group, lactate content increased as compared to both preoperative levels and the levels immediately after liver resection. A significant difference in AST activity levels between the groups was registered on Day 5, although this difference was not clinically relevant. The decrease in the prothrombin index in the study group on Day 3 was superior to that in the control group. The multiple regression analysis demonstrated a moderate positive association between the number of resected liver segments and the markers of the functional state of the liver in the study group while in the control group, such association was not significant.

Conclusion: The protective effect of sevoflurane on the postoperative function of the liver is manifested by the lower level of blood lactate and the stable level of transaminase activity.

Testicular cancer is the most common neoplasm in young males. The early diagnosis and the appropriate treatment make it a curable malignancy in over 90% of the patients, but 6% of the patients with testicular cancer develop a second, mostly treatment-related, malignancy in another primary site many years after the first diagnosis. The simultaneous appearance of a testicular tumor with another primary neoplasm is rarely described in the literature. Here is presented an interesting case of a coexisting non-seminomatous germ cell testicular tumor with a papillary thyroid carcinoma, which was detected early during post-treatment restaging of the testicular tumor. The synchronous presence of these two neoplasms might indicate a probable common pathogenetic background. As treatment-related oncogenesis is highly improbable in this case and the common environmental factors are not known yet, the interest is focused on genetic predisposition. Recent discoveries in molecular genetics show that the two neoplasms share common genetic alterations in the RAS and BRAF genes, which affect the significant signaling pathways. Interestingly, BRAF-V600E was positive in both primary malignancies in our individual.

Background: Thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) are expressed in various cancer cells. However, their role in cancer development is not well defined.

Aim: To investigate the effects of anti-TSLPR antibody on the viability, proapoptotic genes expression, and production of pro-inflammatory cytokines in MCF-7 and A549 cancer cells.

Materials and methods: MCF-7 and A549 cells were exposed to anti-TSLPR monoclonal antibody for 24, 48, and 72 h. The effect on cell viability was examined by MTT assay. The expression levels of TP53, BAX, and CASP3 genes were evaluated by the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Levels of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and transforming growth factor (TGF-β1) were measured by the enzyme-linked immunosorbent assay (ELISA).

Results: The treatment of MCF-7 cells with anti- TSLPR antibody slightly stimulates cell proliferation after 48 h and 72 h following initial cytotoxicity in 24 h with a significant reduction in IL-6 and TNF-α production. A significant increase in the BAX expression in anti-TSLPR treated cells at a concentration of 2.5 μg/ml at 24-h point was evident. In anti-TSLPR-treated A549 cells, no decrease in cell count was observed, and slight dose-dependent stimulation of cell proliferation was evident in 48 h and 72 h of culture. A significant increase in TP53, BAX, and CASP3 expression upon treatment with 2.5 μg/ml of anti-TSLPR was evident in A549 cells.

Conclusion: The effects of anti-TSLPR on cell viability, proapoptotic gene expression, and production of pro-inflammatory cytokines (IL-6 and TNF-α) vary in MCF-7 and A549 cells.

Background: Red rice bran extract (RRBE) contains many biologically active substances exerting antioxidant and anti-inflammatory effects.

Aim: To evaluate the anticancer potential of RRBE in human colon cancer cells and its mutagenic/antimutagenic effects on nonmalignant cells.

Materials and methods: The cytotoxic effect of RRBE was determined by trypan blue exclusion in HCT116, HT29 cell lines and a non-cancerous HEK293 cell line, and its antiproliferative effect using MTS and colony formation assay. The apoptosis induction was evaluated using ELISA, and the apoptotic rate and cell cycle progression were assessed by flow cytometry. The mutagenic/ antimutagenic potential of RRBE was analyzed by micronucleus assay in the V79 cell line.

Results: RRBE caused a dose-dependent reduction of cell viability in colon cancer cells and showed a limited cytotoxicity against HEK293 cells. The treatment with RRBE suppressed proliferation of HCT116 and HT29 cells and induced apoptosis as evidenced by the increased DNA fragmentation and the apoptotic cell counts. Furthermore, RRBE treatment significantly increased the number of cells at the G2/M phase triggering the arrest of the cell cycle in colon cancer cells. Interestingly, RRBE did not increase the micronucleus frequency in V79 cells but reduced the micronucleus formation caused by mitomycin C.

Conclusion: RRBE effectively suppressed proliferation, induced apoptosis, and caused a cell cycle arrest in human colon cancer cells while being non-mutagenic and exerting antimutagenic effects in vitro.