Experimental oncology最新文献

Background: Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients.

Aim: To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients.

Materials and methods: The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction.

Results: Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes.

Conclusion: Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.

With deep sadness, we announce that on December 10, 2023, at the age of 86 passed away an outstanding Ukrainian scientist in the field of oncology, analytical enzymology, and pharmacology, a Laureate of the State Prize of Ukraine for Science and Technology, a member of the Federation of European Biochemical Societies, a member of the State Expert Center of the Ministry of Health of Ukraine, Doctor of Medical Sciences, Professor Volodymyr Oleksiyovych SHLYAKHOVENKO.

Background: In 2020, a sharp decrease in the number of new cancer cases was registered in Ukraine in the setting of the quarantine restrictions due to the COVID-19 pandemic, which contrasted with the previous trends.

Aim: To study trends of cancer incidence rates in Ukraine in the recent decade and to assess the impact of COVID-19 pandemic on cancer detection in 2020.

Materials and methods: Records on cancer cases diagnosed during 2010-2020 (n = 1,498,911) from the database of the National Cancer Registry of Ukraine were used; the data being submitted early in 2022. Trends of the age-standardized incidence rates in 2010-2019 were estimated by the Joinpoint Regression Program.

Results: During 2010-2019, the incidence rates increased (p < 0.05) for colon, prostate, and pharyngeal cancers in males and for colon, thyroid, and pancreas in females with the rates of other prevalent cancers being stable or decreasing (lung and larynx in males, cervix and rectum in females, stomach in both genders); the incidence increased mainly at the expense of the population aged 60-74 years. A significant decrease in cancer incidence was in males aged 40-59 years. In 2020, the serious negative impact of COVID-19 outbreak on the timely detection of cancer occurred in all adult age groups of the Ukrainian population and involved all the most common cancers. The most pronounced diminution of the incidence rate was observed for non-melanoma skin cancers (by 35.9%- 37.9%); the decrements of the rates for other prevalent cancers varied from -23.0% (prostate gland) to -9.7% (pharynx) in males and from -21.2% (kidney) to -9.1% (pancreas) in females, the greatest ones being in the population aged 75+.

Conclusions: The sharp drop of the cancer incidence rates registered in Ukraine 2020 is evidently the result of the limited access to healthcare facilities as well as the reduced oncological alertness of the population due to the predominant focus on COVID-19 during the pandemic. However, it is not a manifestation of a decrease in cancer incidence as such. In the following years, this may increase the proportion of advanced-stage diagnoses, the load on the cancer care system, and cancer mortality in the Ukrainian population. An evaluation of the short-termand long-term effects of the COVID-19 pandemic on the cancer burden in Ukraine requires further monitoring.

The term Mixed Adeno-Neuro-Endocrine Carcinoma (MANEC) was introduced in 2010 by the WHO Classification of Tumors of the Digestive System. It refers to a neoplasm with dual epithelial and neuroendocrine differentiation, each component representing at least 30% of the tumor. It is an uncommon tumor accounting for < 3% of all colon and rectum malignancies. We report three cases of this extremely rare MANEC of the rectum. All three cases presented with hematochezia, variable constipation, and abdominal pain. They were diagnosed and staged appropriately with colonoscopy, biopsy with immunohistochemistry, and imaging. They underwent an anterior resection with circular stapled anastomoses. Because of the low incidence of this histotype, we reviewed the clinical presentation, diagnostic characteristics, and treatment of MANEC of the colon and rectum.

Background: SLAMF1/CD150 is an active player in B cell signaling networks in chronic lymphocytic leukemia (CLL). CD150-mediated signaling initiates through a homophilic CD150 binding, which spans the adjacent cells, or the interaction with the soluble CD150 isoform (sCD150). The expression of sCD150 isoform at the mRNA and protein levels ex vivo was confirmed. However, it is unclear whether sCD150 isoform present in the blood plasma of CLL patients is a factor in the constitutive activation of CD150+ cells. The aim of this study was to develop an ELISA assay for the specific sCD150 evaluation and assess the sCD150 levels in the blood plasma of CLL patients with different CD150 expression on B cells.

Materials and methods: Blood plasma samples and peripheral blood mononuclear cells from 40 previously untreated CLL patients were analyzed. An ELISA method, ex vivo drug sensitivity assay, and a cell viability assay were used.

Results: The sCD150 isoform was found in all studied plasma samples of CLL patients at different levels regardless of the cell surface CD150 expression status of B cells and sCD150 mRNA expression. CLL cases with low levels of the cell surface CD150 expression in B cells are characterized by high levels of sCD150 in blood plasma in contrast to the CLL cases with high cell surface CD150 expression on B cells. The elevated levels of sCD150 in blood plasma are associated with a better sensitivity of malignant B cells to cyclophosphamide and bendamustine.

Conclusions: The sCD150 isoform is actively secreted by CLL B cells with its accumulation in blood plasma, which may be regarded as an additional factor in the CLL clinicopathologic variability.

Today, methotrexate (MTX) is used in combination with other medicines to treat a wide range of malignancies. Despite its proven high efficacy, MTX often causes serious side effects, which may result in the need to reduce the dose of MTX or discontinue the drug altogether. This, in turn, can provoke the development of MTX resistance and cancer progression. Predicting the risk of MTX-induced toxicity is currently difficult due to the variability of pharmacokinetics and pharmacodynamics in different patients, so the scientific literature is intensively searching for potential biomarkers. Based on the data available in the current literature, we analyzed the relationship between variants in the genes encoding the key components of MTX intracellular metabolism and the MTX-induced side effects and drug response. According to the results of our work, the most studied variants are those of the SLC19A1 gene, which encodes the reduced folate carrier protein 1, and the MTHFR gene, which encodes the enzyme methylenetetrahydrofolate reductase. Studies of the effect of methylation of the promoter regions of genes on the therapeutic effect of MTX are also very promising. In conclusion, the study of molecular genetic markers of MTX toxicity is extremely relevant and necessary because it can help to avoid the effect of multidrug resistance and improve the quality of life and survival of patients.

Nobel Symposium 175 was organized by Professor Richard Rosenquist Brandell of Karolinska Institutet and was supported by the Royal Swedish Academy of Sciences. The focus of the symposium was a discussion on the development of precision medicine in infectious and rare diseases, cancer, and complex diseases. Presentations and discussions concerned new technologies, bioinformatics, and new diagnostic and therapeutic approaches based on findings in basic research. Organization of precision medicine models and their implementation in medical practice at the national and international levels were also on the agenda. 29 scientists from different fields of medicine presented their work during a three-day exciting trip into the future of patient' care. Panel discussions shed light on the development of precision medicine for better treatment of patients.

Background: Breast cancer (BC) stands out as the most prevalent cancer in women. The levels of miRNA expression before and after chemotherapy are considered a potential indicator for the prognosis of the disease.

Aim: To study blood plasma miRNA levels in BC patients and to assess their correlation with the menopausal status, disease stage, and molecular BC subtype.

Materials and methods: Blood plasma levels of 6 miRNAs (miRNA-25, miRNA-27, miRNA-155, miRNA-200, miRNA-335, and miRNA-497) were studied in 70 BC patients and 18 healthy individuals using RT-PCR.

Results: miRNA-25, miRNA-335, and miRNA-497 levels were significantly higher in BC patients, while a tendency toward a decrease in the miRNA-27 and miRNA-335 levels in premenopausal patients and high miRNA-27 levels in menopausal patients was established. After neoadjuvant chemotherapy, a decrease in the miRNA-25 and miRNA-335 levels was registered.

Conclusions: The results indicated that miRNA-25, miRNA-27, miRNA-335, and miRNA-497 deserve attention as markers for assessing the efficacy of treatment of BC patients.

Background: The current studies demonstrate that SARS-CoV-2 infection results in increasing complications incidence and the total risk of death in cancer patients. SARS-CoV-2 infection triggers oxidative stress representing one of the major factors of the inflammation contributing to the complicated course of the diseases including cancer.

Aim: To assess the effect of hypoxia caused by SARS-CoV-2 infection on the redox status of blood in patients with metastatic colorectal cancer (mCRC).

Materials and methods: 10 patients with SARS-CoV-2, 11 mCRC patients with metachronous liver disease, and 14 mCRC patients with preceding SARS-CoV-2 infection were included in the study. The data on blood biochemistry (C-reactive protein, ferritin, transferrin, and free iron) were analyzed. The levels of superoxide radicals (ROS) in blood cells were determined by electron paramagnetic resonance (EPR) using the spin trap technique. The metalloproteinase activity was measured by polyacrylamide gel zymography with the addition of gelatin as a substrate.

Results: In mCRC patients with prior SARS-CoV-2 infection, a 1.26-fold increase in ROS-generating activity of blood neutrophils was observed compared to mCRC patients with no history of SARS-CoV-2 infection. The blood content of C-reactive protein, transferrin, and free iron in mCRC patients with prior SARS-CoV-2 infection increased by 2, 6, and 1.4 times, respectively. The total activity of gelatinases in platelets and neutrophils in the blood of mCRC patients with prior SARS-CoV-2 infection was 1.4 and 1.2 times higher compared to mCRC patients with no history of SARS-CoV-2 infection.

Conclusion: mCRC patients with prior COVID-19 have a higher risk of exacerbation of inflammatory reactions. SARS-CoV-2 infection results in redox dіsbalance, which may contribute to the unfavorable course of the disease.

With deep sadness, we announce that on November 29, 2023, at the age of 81, passed away an outstanding Ukrainian scientist in the field of biomaterials and sorption therapy, a member of the European and International Societies of Artificial Organs, a laureate of the State Prize of the USSR, an Honored Worker of Science and Technology of Ukraine, Doctor of Medical Sciences, Professor, Corresponding Member of the National Academy of Sciences of Ukraine Volodymyr Gryhorovych NIKOLAEV.