The aim of the study was to summarize the available data on the relationship between adipose tissue mediators and cancer in patients with metabolic syndrome. Material and methods. A literature search was conducted using the PubMed and eliBRARY databases. Of the 400 articles published over the past 20 years, 58 studies were included in the review. Results. There is evidence of an unfavorable course of cancer in patients with metabolic syndrome that is explained by the presence of common pathogenetic pathways. In this review, special attention is paid to adipose tissue mediators that regulate the course of inflammation. The involvement of adipose tissue mediators in the pathogenesis of cancer is discussed. The relationship between adipokines of adipose tissue and the effects of specialized pro-resolving mediators (SpRM), which are metabolites of polyunsaturated fatty acids (resolvins, protectins and maresins), are considered. the associations of mediators that regulate the intensity of inflammation with the metabolic syndrome and cancer are discussed. Conclusion. Further studies will contribute to a better understanding of the relationship between metabolic syndrome and cancer and the search for adequate predictive markers to select the most effective drug strategy for correcting metabolic syndrome.
Background . Despite the improvement in combined modality treatment of early breast cancer (BC), the rate of locoregional recurrence remains in the range of 7-15 %. Therefore, the search for prognostic factors for BC is of great significance. The aim of the study was to estimate the relationship between clinical and morphological parameters and 10-year recurrence-free survival rate in BC patients after combined modality treatment including intraoperative radiotherapy (IOLT). Material and Methods . The study enrolled 383 patients with morphologically verified T1-3N0-1M0 stage breast cancer. The median age of the patients was 53 years (range: 28 to 80 years). All patients underwent breast-conserving surgery with IOLT delivered to the tumor bed at a single dose of 10 Gy (24.8 Gy according to the iso-effect). External beam radiation therapy (EBRT) to the conserved breast was given in the postoperative period. Results . Within the 10-year follow-up, 20 (5.2 %) locoregional recurrences occurred, of which 7 (35 %) developed with a primary tumor size of ≤ 2 cm (T1), and most recurrences - 13 (65 %) were detected with the primary tumor size corresponding to T2-3. In patients with luminal A subtype of BC and in patients with triple negative BC, the recurrence rates were 5 % and 45 %, respectively. The 10-year survival rate of patients after combined modality treatment with IOLT was 94.8 %. Conclusion . The results obtained indicate the relationship between the recurrence rate and clinical/ morphological parameters of the tumor, such as tumor size and molecular subtype. These parameters should be taken into account when planning treatment in patients with early BC.
Introduction . Ovarian cancer (OC) is one of the malignant neoplasms of the female reproductive system with a high mortality rate. Currently used tumor markers of this pathology do not have high sensitivity and specificity. In this regard, promising areas of molecular oncology are the study of the mechanisms of carcinogenesis of OC and the search for new biomarkers of liquid biopsy for early non-invasive diagnosis of neoplasms. It is known that tumor cells actively secrete exosomes into the extracellular space, which include biologically active molecules involved in carcinogenesis and claiming to be diagnostic markers. It was previously shown that microRNA-24 (miR-24) and microRNA-101 (miR-101) are transported as part of exosomes in OC and are involved in the degradation of the extracellular matrix, stromal remodeling, angiogenesis, and cancer cell motility. Aim . To evaluate the representation and diagnostic significance of miR-24 and miR-101 in plasma exosomes and ascitic fluid of OC patients. Materials and methods . The study included blood and ascitic fluid samples from OC patients ( n = 20) and blood samples from healthy women ( n = 19). The exosomal nature of the vesicles was confirmed by transmission electron microscopy, nanotracing analysis, and flow cytometry. After isolation of exosomal RNA, the relative level of miRNA was determined using reverse transcription and real-time polymerase chain reaction. Results . The highest concentration of exosomes was found in the ascitic fluid of OC patients, while the concentration of exosomes in the blood plasma of these patients was significantly higher than in healthy women. Relative levels of miR-24 and miR-101 in exosomes of blood plasma of healthy women were significantly higher than in exosomes of blood plasma and ascitic fluid of OC patients; at the same time, the levels of these miRNAs in exosomes of plasma and ascitic fluid of patients did not differ significantly. Conclusion . The results obtained confirm the promise of exosomal miR-101 and miR-24 for the diagnosis of OC by liquid biopsy.
Metabolic reprogramming has become the new hallmark of cancer. Carbohydrate metabolism is a key component of metabolic transformations in tumors. To date, many therapeutic agents have been identified that target proteins and enzymes involved in glucose transport and metabolism, with promising results in cell culture studies and animal tumor models. In our studies, we found that the most promising among them is the glycolysis inhibitor iodoacetate. The study of this agent showed that iodoacetate in liposomal form has the best performance. With a course introduction, its antimetastatic and antitumor activity reached significant indices of growth inhibition. At the same time, liposomes with iodoacetate had an almost completely safe toxicological profile compared to the independent form and, as a result, have great potential in polychemotherapy.
Proteasomes, the most important participants in protein catabolism, maintain proteostasis and regulate cellular processes in ontogeny. Deviations in the functioning of proteasomes are associated with the development of various pathologies, including a number of oncological diseases. In this work, we studied changes in subunit gene expression and proteasome activity in laryngeal cancer tissue and epithelium of patients with chronic hyperplastic diseases of the larynx, which are considered obligate precancer. The activity of circulating proteasomes was also studied in the same groups of patients. The level of gene expression was assessed using quantitative reverse transcriptase followed by PCR in real time. A method for assessing chymotrypsin-like (CTL) and caspase-like (CL) activities of proteasomes has been modified for the analysis of small volumes of biopsy samples. An increase in the level of expression of the proteasome genes ( PSMB6 , PSMB7 , PSMB5 , and PSMB4 ) in the tissues of squamous cell carcinoma of the larynx was shown compared to pretumor samples. An increase in CTL and CL activities of intracellular proteasomes in the malignant epithelium of the larynx was also found in comparison with the conditionally normal tissue and with the epithelium of patients with chronic hyperplastic diseases of the larynx. An increase in chymotrypsin-like activity was observed in circulating proteasomes. ROC-analysis (Receiver operating characteristic) revealed the relationship between PSMB5 mRNA expression and CTL activity of tissue proteasomes with the development of laryngeal cancer in patients with chronic hyperplastic diseases of the larynx. In the future, it is possible to use these indicators to develop a method for predicting the transition of precancer of larynx to cancer.
A liposomal form of anticancer drugs is often used to improve pharmacokinetics and reduce systemic toxicity of the drugs. The goal of the study is to develop a method for quantitative analysis of a liposomal form of sodium iodoacetate (IA), glycolysis inhibitor, which exhibits a pronounced antitumor activity. Liposomes were prepared by extrusion at a temperature of 25 – 55°C under argon pressure ranged from 2 to 10 MPa. The obtained liposomes were purified from the non-incorporated component using dialysis. The method of HPLC was used to analyze the inhibitor solution in liposomes. The method of hydrophilic interaction chromatography revealed a high selectivity of iodoacetate with aminopropyl silica gel as a stationary phase. The best option for analysis was to use a spectrophotometric detector. The results of analysis showed that the dose of the inhibitor in 1 ml of liposomes was 0.20 – 0.23 mg regardless of the liposome size. In terms of the weight of an animal, the amount of iodoacetate was 8 – 9 mg/kg. The analysis of liposomes by the developed method showed that the highest yield and a high degree of purification is attained at low temperature (no more than 40°C) and duration of dialysis for about 3 h. For these purposes, the use of liposomes with a diameter of 400 nm turned out to be the best option.
— The function of a newly discovered protein is often assessed by matching its new sequence to sequences of proteins with known functions. However, protein superfamilies can contain homologous elements that catalyze different reactions. Some homologous proteins differ in that they perform a second or even a third function and are called moonlighting proteins, which can be translated as compatible proteins or part-time proteins. Also, such proteins are called multifunctional. In addition to these, the superfamilies of proteins with multiple functions also include pseudoenzymes that have a common catalytically active domain but no catalytic activity, as well as metamorphs and morpheins. This review discusses examples of such proteins, their diversity of functions, and their importance in the life of the cell.
Objective of the study: To review worldwide literature data on the efficacy of combined modality treatment including intraoperative radiation therapy (IORT) in patients with operable breast cancer (BC). Material and Мethods. Of 110 publications (2000–2021) available from Scopus, Pubmed, Elibrary and other databases, using the key “breast cancer”, “local recurrence”, “intraoperative radiotherapy” and “radiation technique”, 45 were included in the literature review. Results. Radiotherapy is of paramount importance in the organpreserving treatment of breast cancer, as numerous randomised studies have shown that the use of postoperative radiotherapy dramatically reduces the number of locoregional recurrences. The use of IORT as an effective method of relapse prevention compared to standard postoperative adjuvant radiotherapy is an important trend in radiation oncology.Conclusion. The use of IORT in combination treatment modality for operable breast cancer should be differentiated and based on clinical and morphological prognostic factors. Different molecular subtypes of breast cancer are characterized by significant differences in pathogenesis and response to therapy. Further studies on the effectiveness of IORT are required to identify a group of patients with absolute indications for the use of IORT.
We previously exposed the role of actin-binding proteins (ABPs) in cancer development and progression. In this paper, we studied the relationship between circulating ABPs and the number of ABP-expressing leukocytes and circulating tumor cells (CTCs) in patients with highly aggressive laryngeal squamous cell carcinoma (LSCC). The levels of cofilin (CFL1), profilin (PFN1), ezrin (EZR), fascin (FSCN1), and adenylate cyclase-associated protein 1 (CAP1) were determined using enzyme immunoassay. The ABP expression by the cellular pools was analyzed by flow cytometry. The highest levels of FSCN1 and EZR were found in the blood serum of LSCC patients. There was a difference in ABP expression between the pools of leukocytes and CTCs. Leukocytes were mainly represented by CAP1+ and FSCN1+ pools, and CTCs contained CAP1+, FSCN1+, and EZR+ cells. The serum FSCN1 level correlated with the number of FSCN1-containing and CFL1-containing leukocytes. Thus, the level of circulating EZR is likely related to its expression in CTCs. The levels of CFL1 and PFN1 are likely to be supported by the expression of these proteins by leukocytes. Both CTCs and leukocytes can be a source of FSCN1 and CAP1 in blood serum. The results suggest that serum proteins can be produced by various cells, thus indicating both cancer development and the response of the immune system to this process.
Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA levels of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAI1 and RND3 and SCCLH metastasis. The serum levels of the above ABPs were estimated and the relationship between them and their mRNA expressions was analyzed. The expression levels of ABP mRNAs were measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T1-4N0-1M0). Expression analysis was performed using the 2−ΔΔCT method. The levels of ABPs in the blood serum were measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. No significant difference in the mRNA gene expression in tumor tissue of patients with T1-3N0M0 SCCLH and patients with T2-4N1-2M0 SCCLH was found. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T2-4N1-2M0 patients, the level of PFN1 was lower by 21% and the level of CAP1 was higher by 75% than those observed in T1-4N0M0 patients. The data obtained showed that RND3 is involved in the regulation of molecular cascades of SCCLH metastasis. PFN1 and CAP1 serum levels can be good classifiers of metastases in patients with SCCLH.
The biological aggressiveness of a tumor is determined by the ability of tumor cells to invade and metastasize which is a consequence of their acquisition of a number of phenotypic characteristics. Remodeling of the actin cytoskeleton occurs during cell migration which is carried out by various groups of actin binding proteins in the regulation of which proteasomes and calpains play an important role. Therefore the study of the relationship of proteins associated with cell motility with the processes of lymphogenous metastasis as well as the assessment of the regulatory role of intracellular proteases in these processes is extremely important for fundamental oncology. This study demonstrates the associations of actin-binding proteins with the activity of proteasomes and calpain, which are specific for tumors and metastases of the mammary gland. We proposed a possible scheme of the relationship of intracellular systems with the actin-binding proteins. The results obtained expand the fundamental understanding of the processes of tumor progression and can also be used in the search for proteins-targets for therapeutic action in molecular targeted cancer therapy.