Experimental oncology最新文献

Background: Imaging plays an important role in the identification of prostate cancer (PCa). However, a shortcoming of the current imaging techniques is their inability to detect PCa at an early stage of development when tumor volume is small. This led us to explore new and improved imaging methods. The phenomenon that infrared (IR) light penetrates biological tissues caused our efforts to utilize IR rays for PCa visualization. The aim of this study was to conduct model experiments to demonstrate how IR light could be used in the future to detect PCa in vivo.

Materials and methods: Experiments were carried out on prostates obtained after radical prostatectomy. The study was approved by the ethical commission of the Georgia-Israel Joint Clinic "Gidmedi". We developed a device that uses IR light to illuminate a prostate from the inside. In order to get IR images of the prostate, we developed a device with an IR-sensitive charge-coupled device (CCD) camera. The model experiments showed that the intensity of IR light passing through noncancerous and malignant prostate tissues is significantly different allowing their distinguishment. The visualization device can detect PCa lesions as small as several millimeters.

Conclusion: These results suggest that our device could be useful for the detection of small PCa lesions.

The study aimed to identify the clinically relevant gene variants in colon adenocarcinoma samples of Ukrainian patients using the NGS Comprehensive Cancer Panel (CCP) to implement them conveniently in clinical practice.

Methods: We have studied 20 samples of Ukrainian patients with colorectal adenocarcinomas of various differentiation grades. To identify the clinically relevant gene variants, the CCP data were filtered using the Franklin by Genoox database.

Results: A total of 79 clinically relevant gene variant alterations (SNVs, INDELs) were found in 28 of 409 genes. The largest number of mutations was found in 3 genes, APC, TP53, and KRAS (16, 14, and 8, accordingly). We revealed 4 variants in PTEN and SMAD4, 3 variants in CHEK2, ERBB2, and PIK3CA genes, and 2 variants in AKT1, ATM, DST, IDH1, and TCF12. Mutations for 7 genes, KRAS, TP53, CHEK2, PTEN, AKT1, APC, and SMAD4, were found in more than 1 tumor tissue sample. Tier 1-2 gene variants rate was about 50% of all genetic variants. The therapeutic significance was found in more than 55% of mutations. Additionally, 11 novel genetic mutations in 9 genes have been identified, including G6PD, APC, DST, SINE1, SMAD2, and FLCN.

Conclusions: These data suggest a high level of clinical relevance of the NGS CCP approach. Further confirmation on a larger number of samples and using a deeper analysis by other approaches is required.

Aim: To compare the expression of miRNA-185-5p and miRNA-424-5p in tumor cells and peripheral blood serum (PBS) of patients with endometrioid carcinoma of the endometrium (ECE) and to evaluate the significance of these biomarkers in cancer progression.

Materials and methods: The study was conducted on the samples of peripheral blood serum (PBS) and tumor tissue of 58 patients with stage I ECE using clinical and morphological methods and real-time polymerase chain reaction.

Results: A significant increase in the levels of circulating and tumor-associated miRNA-424-5p was established in ECE patients with a history of recurrences compared to patients without recurrences. To the contrary, the expression level of miRNA-185-5p increased in the PBS and decreased in the tumor tissue of ECE patients with recurrences compared to the patients without recurrence. In addition, we revealed that the expression levels of the studied miRNAs were associated with the differentiation grade and degree of tumor invasion. We established that miRNA-424-5p levels in PBS could serve as the most significant indicator for predicting the occurrence of recurrence in patients with ECE (AUC = 0.991; Sp 94.0%; Se 99.9%).

Conclusions: The expression features of miRNA-185-5p and miRNA-424-5p in the PBS and tumor tissue of patients with ECE are associated with the aggressiveness of cancer course and the risk of recurrence.

Background: The development of new approaches to modeling tumor radiosensitivity in patients with head and neck squamous cell carcinoma (HNSCC) is an important problem for overcoming tumor radioresistance. New agents for radiomodification are inhibitors of the enzyme cyclooxygenase-2 (COX-2). The study of markers of radioresistance in cancer patients undergoing radiotherapy (RT) in combination with COX-2 inhibitors and chemotherapy may contribute to the effectiveness of RT.

Aim: To determine the effect of conformal RT in combination with radiomodifiers (celecoxib, cisplatin, or their combination) on the content of vascular endothelial growth factor (VEGF), COX-2, and prostaglandin E-2 (PGE-2) in the serum of patients with HNSCC.

Materials and methods: 47 patients with HNSCC were divided into 4 groups: RT in combination with celecoxib and cisplatin, RT with cisplatin, RT with celecoxib, and RT. Patients received radiation treatment on a Clinac 600C linear accelerator. The levels of VEGF, COX-2, and PGE-2 in the serum were determined by enzyme immunoassay.

Results: Blocking COX-2 in patients with HNSCC leads to a decrease in VEGF levels. The largest decrease in VEGF levels was observed in a group treated by RT in combination with celecoxib and cisplatin, indicating a more effective antiangiogenic effect. The changes in the levels of VEGF, COX-2, and PGE-2, which are most pronounced under the combined effect of RT and both radiomodifiers, coincided with an objective response to radiation treatment.

Conclusions: The data obtained indicate the effect of radiomodification on the suppression of angiogenesis, which is most pronounced under the combined effect of RT and both radiomodifiers. The decrease in the levels of PGE- 2, COX-2, and VEGF coincides with the clinical efficacy of radiotherapy according to RECIST 1.1 criteria.

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.

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.

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.