Experimental oncology最新文献

Background: Multiple myeloma (MM) is the most common type of paraproteinemic hemoblastosis, which is characterized by an aggressive course, high mortality and a large number of complications. The G681A variant (*2, rs4244285) of the CYP2C19 gene leads to the formation of an inactive enzyme and, as a consequence, may affect the development and course of MM. The aim of this research was to analyze the effect of the G681A variant of the CYP2C19 gene on the risk of the development of MM and its course.

Materials and methods: The study enrolled 158 patients with MM, who underwent standard clinical and laboratory studies: cytological, general clinical, biochemical, as well as molecular cytogenetic and molecular genetic. Cytogenetic analysis of chromosome abnormalities was performed using interphase fluorescence in situ hybridization. Genotyping by the G681A variant of the CYP2C19 gene was performed by polymerase chain reaction-restriction fragment length polymorphism.

Results: No association was found between the G681A variant of the CYP2C19 gene and the risk of developing MM. The association between the presence of the G allele and GG genotypes with significant changes in clinical and biochemical parameters (plasma cell count, α2-globulin, calcium content) in MM patients has been established. In the presence of the G allele of the CYP2C19 gene, the development of chromosomal rearrangements del(13q14.2) or del(13q34) with significantly increased levels of albumin occurs more frequently.

Conclusions: The G681A variant of the CYP2C19 gene does not affect the risk of developing MM, but it is associated with significant changes in the clinical and biochemical parameters that determine the severity of the disease and its prognosis. Further research is important to develop new target strategies and maintenance therapy for carriers of different variants of the CYP2C19 gene (G681A).

Aim: To evaluate the influence of dispersed fibrous carbon sorbent (DFCS) on malignant fungating wounds (MFWs) in Guerin's carcinoma-bearing rats with an assessment of wound bacterial microflora.

Materials and methods: The study was performed on female Wistar rats inoculated subcutaneously with Guerin T8 carcinoma into the upper interscapular region. On day 20, the tumors were infected by injecting the suspension of S. aureus 8325-4. After 24 h, gauze dressings were applied daily to the wounds in the control group and DFCS in the experimental one. The state of the wounds was assessed by visual control with photo monitoring, odor control on a verbal rating scale and microbiological analysis of qualitative and quantitative characteristics of wound microbiota.

Results: On the 3rd day after the start of dressings, the number of S. aureus of 8325-4 strain was significantly higher in the wounds of rats in control group than experimental one (5.14 ± 0.27 vs 3.43 ± 0.33 lg CFU/ml). The total number of Staphylococci in the DFCS-treated wounds did not differ statistically from the number of S. aureus 8325-4 strain whereas in control ones were higher by an order of magnitude. On the 10th day the total number of Staphylococci and S. aureus 8325-4 in particular, remained consistently high in the wounds of the control rats, while was almost five orders of magnitude lower and represented mainly by S. aureus 8325-4 in the experimental ones. The total number of aerobic and optionally anaerobic microorganisms was significantly lower as well. A greater variety of microorganisms in the gauze-covered wounds, as well as an their increased number were accompanied by enhancement of the wound odor from "noticeable" to "strong". There was an appearance of a "barely noticeable" odor in only one animal from the experimental group.

Conclusion: The study has demonstrated the ability of DFCS to control substantially the bacterial microflora as well as malodor of MWFs in vivo. The results obtained can contribute to solving the problem of improving the quality of palliative care for patients with malignant and other chronic wounds.

Background: Classification of breast cancer (BC) in the molecular subtypes had the enormous impact on the development of the individualized therapy. Nevertheless, there is a need for additional biomarkers that would help to refine molecular subtypes of BC and propose the therapeutic approach for each patient.

Aim: To study differential expression patterns of AIP, UCKL1, and PKN1 genes in blood sera and tumor tissue of patients with BC of different molecular subtypes.

Materials and methods: The total extracellular RNA was isolated from serum of 26 BC patients. cDNAs was synthesized and quantitative polymerase chain reaction was performed. Also, immunohistochemical studies of UCKL, AIP and PKN1 were performed on deparaffined tissue sections. The study was supplemented by a bioinformatic analysis of the publicly available databases.

Results: AIP and UCKL-1 extracellular mRNA levels were 100-1000-fold increased in blood sera of all BC patients, compared to the healthy donors. The highest levels were detected in the luminal A and HER2 (ERRB2) BC subtypes. The highest levels of PKN1 were detected blood sera of the patients with luminal B and basal subtypes; its expression levels were just 10-100-fold higher in BC samples compared to healthy donors.

Conclusions: The UCKL1, AIP, PKN1 genes are overexpressed at the mRNA level in blood sera of BC patients compared to the sera of healthy individuals. Among three genes under study, only for the AIP gene, the pattern of extracellular mRNA expression in sera paralleled to protein expression in BC tissues of each specified molecular subtype.

Our knowledge about the etiology of cancer is increasing. Many studies show that non-intrinsic factors such as environment or lifestyle are the main risk factors for the occurrence of cancer. On the other hand, there are studies showing that the main risk factors in the occurrence of cancer are caused by DNA replication errors (known as the intrinsic factors). This view limits highly the possibility of protection from cancer. However, the findings obtained from the literature show that non-intrinsic factors contribute substantially to cancer risk and that cancer should be considered as a preventable disease. This review is aimed to examine the factors known as non-intrinsic cancer risk factors in the light of recent research.Key Words: cancer, non-intrinsic risk factors, cancer prevention.

Background: T-cell lymphoma (TCL) is a heterogeneous group of lymphoproliferative diseases that account for 10-15% of all non-Hodgkin lymphomas. The aim of the study was to analyze the incidence of TCL in Ukraine, distribution according to subtypes and to assess the results of treatment of patients with TCL depending on lymphoma subtype and clinical-and-laboratory risk factors.

Patients and methods: Data from 70 patients with TCL were analyzed from February 2018 to May 2021. T-cell lymphoid neoplasms were diagnosed according to the 2016 WHO classification. The patients were divided into 4 groups: 1^st (A) - leukemic forms (n = 13) (received SMILE or HyperCVAD +/- auto/alloSCT); 2^nd (B) - nodal T-cell lymphomas (n = 43) (CHOP-like regimens); 3^rd (C) - cutaneous T-cell lymphomas (n = 9) (PUVA therapy, interferon, and methotrexate); 4^th (D) - extranodal T-cell lymphomas (n = 5) (CHOP-like regimens). The response was determined according to the Lugano 2014 criteria.

Results: According to the study results, 5-6% of all non-Hodgkin lymphoma registered in Ukraine in 2018-2020 were T-cell lymphomas. The most common subtype was peripheral TCL (61%). In the studied groups of TCL patients, the overall response rate was 50% (n = 35). 2-years event-free survival rate was 62.27%. 2-years overall survival rate was 65.76%. 18-month progression-free and overall survival in group B was higher versus groups A, C and D. The factors of unfavorable prognosis were bone marrow involvement and the expression of Ki67 > 65% (p = 0.03 and p = 0.006, respectively).

Conclusions: Histologic subtype of T-cell non-Hodgkin lymphoma influence the treatment outcome. The best overall response rate, overall survival rate, progression-free survival were in group of patients with nodal T-cell non-Hodgkin lymphomas, the worst - in patients from leukemic group. Poor prognostic factors are bone marrow involvement, and Ki-67 expression > 65%.

Aim: To determine the prognostic value of tumor-infiltrating lymphocytes (TILs) in colon adenocarcinomas.

Materials and methods: The study was performed on 180 paraffin blocks of operation material from patients diagnosed with adenocarcinoma of the colon, treated at the Kyiv City Oncology Center in 2013-2018. TILs were counted on histological slides stained with hematoxylin-eosin. By TILs count percentage in tumor slides, the samples were divided into three groups: 0-9% TILs (n = 65); 10-39% TILs (n = 79); and > 40% TILs (n = 36).

Results: Kaplan - Meyer estimate showed that the difference in overall survival between groups was significant (p = 0.001). Multivariate Cox's proportional hazard regression model analysis evidenced on significantly better overall survival rates in groups with moderate TILs percentage (hazard ratio 0.54, 95% CI 0.30-0.97, p = 0.042) and high TILs percentage (hazard ratio 0.36, 95% CI 0.13-0.99, p = 0.049), respectively, as compared with low TILs percentage group.

Conclusion: TILs content can be considered as an independent prognostic factor for colon adenocarcinoma and used as an additional tool in routine practice of pathologists.

Aim of this study was to develop and apply an ELISA method for assessment of the levels of endogenous antibodies against benzo[a]pyrene (Bp) in blood sera of lung cancer (LC) patients.

Materials and methods: ELISA was developed and applied for the detection of endogenous idiotypic and anti-idiotypic antibodies against Bp in human blood sera using recombinant human idiotypic and anti-idiotypic antibodies against Bp.

Results: Serum samples of LC patients (n = 22) and healthy donors (n = 24) were analyzed by the new method. Statistical analysis showed that in sera of LC patients the levels of endogenous idiotypic and anti-idiotypic antibodies against Bp were significantly higher than in healthy donors. A logistic regression model for the LC detection utilizing such predictors as the serum levels of idiotypic and anti-idiotypic antibodies against Bp, smoking status, and age, identified LC patients with 83% specificity and 82% sensitivity.

Conclusion: The proposed method could be further developed as additional lung cancer screening tool.

Epithelial-mesenchymal transition is an important component of tumor progression, due to which the cells of malignant neoplasms acquire invasive and migratory properties. Analysis of the literature and our own data show that the activation of proteins involved in epithelial-mesenchymal transition crucially affects the progression of endometrioid carcinoma of the endometrium and the significant variability of their expression could determine the clinical and morphological heterogeneity of this cancer. The most aggressive endometrioid carcinomas of the endometrium are characterized by a hybrid epithelial-mesenchymal phenotype, which is often associated with a collective type of invasion of endometrial tumor cells into the myometrium.

Aim: To investigate the association between SRA1 rs801460 and rs10463297 variants and proliferative type of benign breast disease with atypia development in Ukrainian females.

Materials and methods: 83 individuals diagnosed with proliferative type of benign breast disease with atypia and 115 without atypia were enrolled in the study. The rs801460 and rs10463297 variants genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Hematoxylin and eosin, toluidine blue and van Gieson's picrofuchsin methods were used for sections staining.

Results: It was revealed that SRA1 rs801460-variant is associated with proliferative type of benign breast disease with atypia development both before and after adjustment for risk factors (age, body mass index, age of menarche, oral contraceptives intake and burdened history of breast cancer). The risk for mentioned disease in the individuals with rs801460 TT-genotype is 2.2 times higher (confidence interval 1.010-4.800; p = 0.047) than in individuals with the CC and CT genotypes. No link between SRA1 rs10463297 and proliferative type of benign breast disease with atypia occurrence in Ukrainian females was found.

Conclusion: The present study specified that SRA1 rs801460, but not rs10463297, can be the strong genetic predictor for benign breast disease with atypia in Ukrainian females.

The aim of this study was to determine the rates of recurrences of stage I endometrial cancer (EC) and features of their localization depending on the clinical and pathological characteristics of the tumor and methods of patients' treatment.

Patients and methods: The study included 968 patients with stage I endometrioid EC, who underwent surgical treatment in the Department of Oncogynecology of the National Cancer Institute in 2015-2019. Surveillance of patients lasted from January 2015 to December 2020, with a minimum follow-up period of 1 year from the date of surgery. Adjuvant radiation or chemotherapy was performed depending on the clinical and pathological characteristics of the EC case.

Results: During the follow-up period, recurrences were observed in 7.0% of cases and were most often found in stage IC of low differentiation grade. It was found that during surgical treatment without adjuvant therapy relapses occurred in 12-36 months after the start of treatment, with adjuvant radiation therapy - in 6-18 months, and with adjuvant chemotherapy - in 32-60 months. Recurrences most often occurred in patients with EC who underwent surgical treatment in combination with chemotherapy (p < 0.05). The lowest number of recurrences was recorded among patients who underwent surgery as an only treatment. The best 5-year survival rate was observed in the group of patients with surgical treatment (93%), and the worst - in the patients treated with combination of surgery and chemotherapy (57%). In patients without recurrences, the survival rate after treatment was 97%, while in patients diagnosed with relapses, the survival rate was 65%.

Conclusion: Despite the predominantly favorable course of EC stage I, some patients develop relapses. The rate and localization of recurrences depend on the histological structure of the tumor and treatment regimens of the EC patients.