Experimental oncology最新文献

Ribonucleases (RNases) perform many different functions in living systems. They are responsible for the formation and processing of various ribonucleic acids (RNAs), including the messenger RNA and all types of microRNAs, and determine the duration of the existence of different RNAs in the cell and extracellular environment. RNases are ubiquitously expressed in many tissue types. This short review discusses the major types and main functions of RNases, their homeostatic functions, influence of transcription, immunomodulation, and the role of extracellular RNases in the immune defense mechanisms.

Rhabdoid tumor is a rare and aggressive neoplasm that usually occurs in children and is often localized in the central nervous system and kidneys, but can be found in many other sites. In our case report, we describe a tumor that was found on computed tomography in the thoracic region of a 62-year-old male and was successfully surgically resected. The images and descriptions of our findings and the results of the additional immunohistochemical studies allow us to make the final diagnosis.

Among women, breast cancer is one of the most prevalent cancers. The disease has a complex etiology, with multiple biological pathways contributing to its development. As insulin signaling has mitogenic effects, glucose is a necessary cellular metabolic substrate, and the growth and metastasis of breast cancer are closely related to cellular glucose metabolism. Anti-diabetic medications have drawn increased attention as a potential treatment for breast cancer. Metformin lowers cancer incidence and death rates in patients with type 2 diabetes, according to epidemiologic studies. Preclinical studies conducted in vivo and in vitro offer fascinating new insights into the cellular mechanisms underlying metformin oncostatic action. We present an overview of the mechanisms of anticancer effects of metformin and discuss its potential function as an adjuvant in the treatment of breast cancer.

Background: Patients with hematological malignancies (HM) are considered to have a high risk of developing severe and life-threatening infections including COVID-19 because of immune deficiency and immunosuppressive treatments. Although the COVID pandemic spread worldwide, morbidity and mortality data varied from country to country. A more accurate identification of risk factors would allow the improvement of the clinical management of HM patients.

Aim: This study aimed to determine real-life data - the mortality rate, clinical outcomes, and risk factors affecting mortality in patients with HM and COVID-19 at the Riga East University Hospital (REUH) in Latvia.

Materials and methods: In this retrospective non-interventional cohort study, we included adult patients treated in REUH with ongoing HM and laboratory- confirmed COVID-19 observed between December 1st, 2020, and March 31st, 2023. All data were analyzed using descriptive statistics, binary logistic regression, univariable Cox regression model, and other methods.

Results: We registered 156 patients with 11 different HMs. Multiple myeloma, non-Hodgkin lymphoma, and acute myeloid leukemia were the most common HM. COVID-19 mortality rate was 19.9% (31/156). Factors increasing the risk of death included the severity of COVID-19 (p < 0.001), the accession of bacterial infection (p < 0.001), longer hospital stay (p = 0.037), absolute neutrophil count (ANC) ≤ 0.5 × 109/mm3 (p = 0.014), fever (p = 0.039), and acute myeloid leukemia (p = 0.002). We also confirmed that the mortality in the third pandemic wave was significantly lower than in the second wave (p = 0.002). Although vaccination seemed to be a risk-mitigating factor (58.8% [10/17] of those who died from COVID-19 were not vaccinated), no statistically important correlation was found (p = 0.690).

Conclusion: This survey confirmed that the COVID-19 mortality rate was higher in patients with HM (19.9% [31/156]) than in the population. ANC, severity of COVID-19, accession of bacterial infection, hospital stay, fever, and acute myeloid leukemia were the factors that increased mortality in HM patients.

Background: The ability to metabolic reprogramming is a distinctive feature of metastatically active tumor cells. A classic example of metabolic reprogramming, characteristic of almost all malignant cells, is aerobic glycolysis. Therefore, inhibition of glycolysis in tumor cells is considered a promising strategy for antitumor therapy.

Aim: To generate Lewis lung carcinoma (LLC) cell subpopulation after pretreatment by a lactate dehydrogenase (LDH) inhibitor - oxamate in adhesive growth conditions, and then to study the metabolism of this subpopulation in the anchorage-independent growth conditions.

Materials and methods: LLC cells were cultured without oxamate or with 17 mM oxamate in the adhesive growth conditions with the following transition to the anchorage-independent growth conditions without oxamate. A distribution of LLC cells by cell cycle phases, apoptosis rate, levels of reactive oxygen species (ROS), E-cadherin, and vimentin were determined by flow cytometry. Glucose consumption and lactate production were determined by spectrophotometry.

Results: 48-h oxamate treatment in adhesive growth conditions resulted in a 30% decrease of the total number of LLC cells compared to the control. In 72 h after the transfer of both oxamate-treated and control cells into the anchorage-independent growth condition without oxamate, the number of viable cells pretreated with oxamate was reduced by 17% (p < 0.05) compared to the control cells. However, the distribution of cells by cell cycle phases did not differ. In cells pre-treated with oxamate, the rate of glucose consumption decreased by 20% (p < 0.05), ROS generation was reduced by 17%, vimentin expression decreased by 10% while the rate of lactate production was the same in oxamate-pretreated and control cells.

Conclusion: The cytostatic effect of oxamate demonstrated in adhesive growth conditions persisted for 72 h in the anchorage-independent growth conditions. The absence of differences in the cell cycle phase distribution and a decrease in the ROS generation may indicate the initial stage of overcoming the cytostatic effect of oxamate after 72 h of culturing LLC cells in anchorage- independent growth conditions.

Aim: To investigate the effect of bacteria of the genus Bifidobacterium and the extracellular metabolite of B. subtilis IMV B-7724 on the antitumor immune response of mice with a model tumor.

Materials and methods: The study was conducted on Balb/c mice with transplanted solid Ehrlich adenocarcinoma (ACE). Starting from the 2nd day after the transplantation of tumor cells, the animals of the experimental groups were treated with lectin of B. subtilis IMV B-7724 (s/c, 1 mg/kg of weight), Bifidobacterium animalis (per os, 7 × 105 CFU/mouse) or their combination. The immunological studies were performed on the 21st and 28th days of tumor growth. The functional activity of natural killer cells (NK), cytotoxic T-lymphocytes (CTL), as well as the ability of lymphocytes from the peripheral lymph nodes (PLN) to transform into blast cells under the influence of T- (Con A) and B-cell (LPS) mitogens were determined.

Results: Administration of probiotic components to the mice with ACE led to the activation of innate immune responses, that is, to a significant increase in the cytotoxic activity of NK, especially in the case of their combined use. The NK cytotoxicity index was higher than that in the non-treated ACE-bearing mice and the intact control by 3.7 and 2.1 times, respectively (p < 0.05). Similarly, the highest specific cytotoxic activity of spleen lymphocytes was observed upon the combined use of the microbial preparations: the CTL cytotoxicity index was nearly 2.5-fold higher than in the non-treated ACE-bearing mice. The data on the ability of PLN lymphocytes to transform into blast cells under the influence of Con A and LPS indicated the preservation of the functional activity of lymphocytes in the animals of the experimental groups during ACE growth.

Conclusion: Both B. animalis and lectin of B. subtilis IMV B-7724 have a significant influence on the effectors of the natural and adaptive immunity of mice with ACE. Their combined use was found to be the most effective.

Background: Analysis of immunoglobulin heavy chain gene (IGHV) rearrangements expressed in chronic lymphocytic leukemia (CLL) cells has provided insights into the B-cell receptor (BCR) repertoire in CLL. In more than 40% of CLL patients, (quasi)identical or stereotyped BCR is expressed. The recent data point at the non-stochastic expression of immunoglobulin light lambda (IGLV) or kappa (IGKV) chains as well. Several pairs of IGHV and IGK/LV have been described for some major stereotyped subsets, but most subsets have not been characterized.

Aim: To study the IGK/LV gene expression in stereotyped CLL cases.

Materials and methods: Analysis was performed in a group of 105 CLL patients with stereotyped BCR. The cases with stereotyped BCRs were identified according to Agathangelidis et al. (2021). The IGHV and IGK/LV gene expressions were studied by a polymerase chain reaction followed by direct sequencing.

Results: The expression of the IGK/LV genes in the most presented major stereotyped subsets (#1, #2, #3C3, #4, #6, #28а) was in agreement with the data reported by other authors. For the cases of subsets #5b, #9D1, #9D4, #16, #50, #59, and #77, differences were found. The new data on the IGK/LV gene expression in 55 minor clusters were presented. A number of patterns of the IGK/LV gene expression depending on the phylogenetic clan and mutational status of the IGHV genes have been described.

Conclusion: The non-stochastic distribution of the IGKV/LV gene expression in the individual stereotyped subsets was confirmed. Taking into account the complementary role of the light chains in antigen recognition by the clonotypic BCRs, it was suggested that the subsets with the heterogeneous IGK/LV expression might be reclassified and divided into separate subgroups based on the IGHV and IGK/LV association.

Background: The development of breast cancer (BCa) is largely determined by the characteristics of the tumor microenvironment (ТМЕ), which undergoes significant changes during the progression of the disease. Mast cells (MCs) are among the least studied components of the TME. The aim of the work was to investigate the relationship between the density of infiltration and the functional activity of MCs with indicators of osteopontin (OP) expression in BCa tissue.

Materials and methods: The study was conducted on the postoperative material of 15 patients with fibroadenoma and 78 patients with stage I-II BCa. MCs in the tissue of benign and malignant breast tumors were detected by a histochemical method using toluidine blue. The functional activity of MCs was calculated by the degranulation index. The OP expression in tumor tissue was assessed by the immunohistochemical method.

Results: The density of MCs infiltration and their functional activity are associated with such indicators of BCa malignancy as tumor size, lymph node involvement, tumor grade, molecular subtype, proliferative activity, and PR- and HER2/neu-expression status. A high expression of OP in the stromal component of BCa is associated with the growth of the tumoral MCs population, metastatic lesions in regional lymph nodes, and a low differentiation grade of the tumors. In addition, OP is involved in the regulation of MCs in the tissue of the luminal B and basal molecular BCa subtypes. The level of OP expression in the parenchymal component of BCa is associated with the number of infiltrated MCs in the presence of metastatic lesions of regional lymph nodes.

Conclusions: The identified relationship of OP expression level with the topology and functional activity of MCs in BCa tissue, depending on the clinical status of patients, indicates the prospects for their use in predicting the aggressiveness of the tumor process.

Science and politics have always gone together. This is what happened in our days when Russia's military aggression against Ukraine, which began in 2014, turned into a full-scale military invasion in 2022 and a war of liberation for the independence and freedom of Ukraine. These events dramatically affected not only the fate of millions of citizens but also brought the destruction of fields of science and technology important for the existence of the country.

Background: Chemotherapy of head and neck squamous cell carcinoma (HNSCC) is associated with significant side effects. Antimicrobial peptides (AMPs), which are naturally occurring defense molecules like defensin-1 and LL-37 found in human secretions, have demonstrated potential in prompting tumor cell apoptosis and enhancing the effect of chemotherapeutic agents. However, the anticancer potential of histatin has not yet been thoroughly examined. The aim of the study was to explore the anticancer activity of histatin, an AMP present in human saliva and used alone or in combination with cisplatin in HNSCC cell lines.

Materials and methods: The gene expression of histatin was evaluated in the HSC4 and SCC25 cell lines by qRT-PCR. Cell proliferation was investigated at different concentrations of histatin peptide (His-1), cisplatin, and their combination using an MTT assay.

Results: SCC25 cells expressed both HTN1 (histatin-1) and HTN3 (histatin-3), whereas the HSC4 cell line expressed only HTN1. The combination of exogenous His-1 and cisplatin demonstrated a synergistic anti-proliferative effect against the HNSCC cell lines in a dosedependent manner.

Conclusions: The combination of low-dose cisplatin and histatin inhibits HNSCC cell proliferation. His-1 sensitizes tumor cells to the cytotoxic effects of cisplatin potentially allowing for a reduction in its effective concentration.