ОRIGINAL ARTICLES
Introduction. Current generally accepted clinical and laboratory criteria for antiphospholipid syndrome (APS) have been clearly determined, which include vascular thrombosis and pregnancy complications in patients with circulating antiphospholipid antibodies (aPLs). However, in the last several years, aPLs have become a common finding in patients with malignancies. Accumulating data provide strong evidence for such association and suggests that thrombosis in cancer patients may be related to aPLs activity. According to global publications, aPLs circulation in cancer patients varies from 15 to 74 %, which may be due to differences in clinical characteristics of cancer patients examined as well as distinct interpretations on aPLs diagnostic tests.
Aim: to determine aPLs profile in patients with malignant neoplasms of the female reproductive system, identify an association between aPLs and thrombosis as well as degree of disease progression and outcome.
Materials and Methods. A single-center observational study was conducted with 130 women, among which 70 subjects had adenocarcinoma of the uterine body, cervix and ovaries. 60 age-matched apparently healthy women lacking thrombotic complications were included into control group. All study participants were examined for circulating lupus anticoagulantas well as anti-cardiolipin antibodies (aCLs), anti-β2-glycoprotein 1 antibodies (anti-β2-GР1), annexin V antibodies, and anti-phosphatidylserine-prothrombin complex antibodies (anti-PS-PT) IgG and IgM by using enzyme-linked immunosorbent assay.
Results. Moderate or low aPLs titers were found in 34.2 % of patients with uterine, cervical and ovarian cancer. Ten (14.2 %) of 70 women in main study group had thrombosis so that aPLs were detected only in 5 of 10 women with thrombosis. No significant differences between patients with thrombosis and without thrombotic complications in gynecological cancer were observed. In addition, assessed parameters had no impact on relapse-free survival in cancer patients. However, a significant relation was found between circulating aCLs (IgG, IgM) and anti-PS-PT (IgG, IgM) as well as degree of oncological process. In addition, a significant association was found between aCLs isotype IgG (p = 0.017) and disease relapse.
Conclusion. Although thrombosis along with acute thrombosis is a hallmark of APS patients, they demonstrate other non-thrombotic manifestations, one of which is the impact on tumor growth invasion and progression.
Aim: to study the role of the hemostatic system in pretem delivery in pregnant women who have had COVID-19 in the gestation period from 14 to 16 weeks.
Materials and Methods. A prospective single-center observational study was conducted by enrolling 63 pregnant women with verified COVID-19 at 14–16 weeks of gestation. The main group consisted of 37 patients with preterm birth (PB), comparison group – 26 patients labour activity that occurred at least at gestational age of 37 weeks. Clinical and anamnestic data and dynamic changes in fibrinogen and D-dimer level, activity of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) were analyzed; thrombin generation assay (TGA) was performed.
Results. It was found that severity of COVID-19 infection did not determine the timing of delivery that depended on patient comorbid condition. All PB observations (37 out of 63, 58.7 %) were caused by decompensated placental function manifested by acute obstetrical complications: increasing intrauterine fetal hypoxia (64.9 %) along with intrauterine growth retardation (51.4 %), severe preeclampsia (13.5 %) and premature abruption of the normally located placenta (5.0 %). In both study groups, COVID-19 experienced at 14–16 weeks of pregnancy was associated with coagulation and fibrinolytic imbalances. At the same time, at least 6 weeks post-COVID-19 infection, patients with PB had higher level of the “Peak thrombin” vs. comparison group (3050 vs. 2527 pmol/L; p = 0.0433). Also, patients with term vs. preterm delivery had TF activity decreased significantly: by 47.1% and 28.1%, respectively (p = 0.0546). Patients in preterm delivery group were characterized by fibrinolytic imbalance. At the first time point, suppressed fibrinolysis (PAI-1 level – 18.4 vs. 12.5 ng/ml in the comparison group; p = 0.0209) was concomitant with elevated level of u-PA (1.5 vs. 0.55 ng/ml in comparison group, p = 0.0015), which suggests a potential prolonged immunoinflammatory response in patients with PB. Magnitude of fibrinogen concentration and D-dimer level during post-COVID-19 follow-up study was within the reference values specific to gestational age.
Conclusion. A significant increase in coagulation potential was found and verified by elevated activity of tissue factor and potential to thrombin generation in COVID-19 convalescent patients. In the case of preterm delivery, there was an imbalance in fibrinolysis system revealed by decreased blood fibrinolytic activity elevating along with increasing gestational age.
Aim: to evaluate a role of polymorphic variants rs4149056 SLCO1B1, rs8023580 NR2R2 and rs7910927 JMJD1C in developing obesity-related female breast cancer (BC).
Materials and Methods. A retrospective comparative study was performed on a sample of 1,498 women (358 BC patients and 1,140 control subjects) stratified into 2 groups based on verified obesity: obese (119 BC patients and 253 control subjects) and non-obese (239 BC patients and 887 control subjects). Genotyping of three single nucleotide polymorphisms (SNP) – rs7910927 JMJD1C, rs8023580 NR2F2, rs4149056 SLCO1B1 was performed to be further analyzed separately in each group of obese and non-obese women for associations of such loci and interplay with breast cancer.
Results. Polymorphisms rs8023580 NR2F2, rs4149056 SLCO1B1 and rs7910927 JMJD1C are not independently associated with BC in obese and non-obese women, whereas their interlocus interactions are BC-significant in each of the examined groups (pperm = 0.047 and pperm = 0.0012, respectively). Among obese women, the combination of TC-TT-GG genotypes (for rs8023580–rs4149056–rs7910927) is associated with a low risk of developing BC (β = –2.45), whereas the combination of TC-TC-GG genotypes is associated with increased BC risk (β=1.42). In non-obese women, a combination of the TC-TT-GT genotypes (β = –0.47) has a protective effect on the BC occurrence, and the risk effect is coupled to TC-TC-GT (β = 0.91) and TC-CC-GT (β = 1.45). The appearance of allele C rs4149056 in female genotype and its increased "concentration" results in higher BC risk.
Conclusion. The allele variant C rs4149056 in the interlocus interactions between the SLCO1B1, NR2F2 and JMJD1C genes is a "universal" factor that elevates BC risk in both obese and non-obese women. The genotype GG rs7910927 is BC-significant in interlocus interactions in obese women, whereas in non-obese women it is coupled to the genotype GT rs7910927.
Aim: to assess associations between folate cycle gene polymorphism and neonatal birth weight in pregnant women with fetal growth retardation (FGR) and related functional effects in population of the Central Black Earth Region.
Materials and Methods. 98 cases of women with FGR were enrolled to a retrospective molecular and genetic screening to assess prevalence 5 SNPs (single nucleotide polymorphisms) in genes involved in folic acid cycle and methionine metabolism (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, rs1801394 MTRR).
Results. It was found out that allele A of the rs1801394 MTRR was associated with a lower neonatal birth weight (recessive model: β = –0.34 ± 0.13; p = 0.009). This polymorphic locus exerts crucial functional effects by determining the amino acid substitution in methionine synthase reductase (Ile22Met) localized in the region of modified histones, which mark enhancers and promoters in ectoderm, endoderm and mesoderm cell cultures, primary osteoblast cells, brain, fat nuclei, skeletal muscles, etc. In addition, rs1801394 MTRR is found DNA sites (motifs) responsible for sensitivity to transcription factors STAT and TBX5 being also related to MTRR gene mRNA expression level in subcutaneous and visceral adipose tissue, thyroid gland, fibroblast cell culture as well as various brain regions.
Conclusion. Thus, the allele A of the rs1801394 polymorphism in MTRR gene is a risk factor for a lower neonatal birth weight.
Introduction. Initially discovered as a mechanism to protect host neutrophils from pathogens and prevent spread of infection outside inflammatory site, neutrophil extracellular traps (NETs) have been implicated in progression of other diseases associated with sterile inflammation such as autoimmune diseases, diabetes, and cancer. NETs components (myeloperoxidase, citrullinated histones, cell-free DNA) exhibit manifold effects on tumor cells, thereby emphasizing a need to be aware of the features of biological functions related to their constituents and their place in carcinogenesis to identify major molecular targets for targeted therapy of gynecologic cancers in the future.
Aim: to determine an impact of NETs on tumor progression/metastasis and thrombosis risk in gynecologic cancer.
Materials and Methods. A single-center interventional study was conducted: 70 women with uterine, ovarian and cervical cancer were examined; 60 age-matched apparently healthy women without thrombotic complications were selected as controls. All study participants were examined for myeloperoxidase (MРO), citrullinated histone (сitH3), proinflammatory cytokine interleukin-1β (IL-1β), and neutrophil/lymphocyte ratio (NLR).
Results. Laboratory biomarkers such as MPO (p < 0.001), IL-1β (p < 0.001) and NLR (p = 0.003) were significantly more often elevated in patients with oncological pathology compared to group of healthy women. 32 (45.7 %) of the 70 women with cancer of the reproductive system had metastases. Metastases-related analysis in patients showed significant differences in MPO level (p = 0.002), but not in level of citH3, IL-1β and NLR (p = 0.441, p = 0.159, and p = 0.739, respectively). Elevated citH3 vs. MPO, IL-1β and NLR level was significantly more often associated with developing thrombosis in study patients (p < 0.001).
Conclusion. The results of our study demonstrate that inflammation and NETs components such as MPO and citH3 may be potentially implicated in many aspects of carcinogenesis including tumor metastasis and the risk of developing thrombosis in cancer patients.
REVIEW ARTICLES
Introduction. Today, infertility is a global problem that affects about 48.5 million married couples worldwide. It has been suggested that epigenetic aberrations are of great importance for reproductive health, as they account for an interactive relationship between genomic landscape, interplay with gene environment and disease phenotype. A new understanding on etiology of complex non-Mendelian disease traits has aroused a growing interest in reproductive epigenetics.
Aim: to analyze available publications on epigenetic aspects of male and female infertility as well as nutrition-related risk factors.
Materials and Methods. There was conducted a search for publications in the electronic databases PubMed, Google Scholar and Library to be selected in accordance with PRISMA recommendations. All relevant articles published before November 2023 were included in this review. As a result of the search, there were extracted 530 publications from PubMed, 57 publications – from eLibrary and 23 publications – from Google Scholar. Duplicates and non-full-text article versions were excluded.
Results. Environmental factors play an important role in generation and maintenance of epigenetic marks. DNA methylation abnormalities can lower human fertility. Altered protamine level may affect epigenetic paternally transmitted DNA information. Long-term infertility is associated with a modified methylome in euploid blastocysts primarily affecting regulation of genomic imprinting. Both excess and deficiency of trace elements are associated with adverse pregnancy outcomes, similarly applied infertility.
Conclusion. Despite that epigenetic mechanisms, genes, nutrition and dietary supplements discussed here affect infertility, while a relevant recommended dose has not yet been determined, it was noted that such parameters may positively influence fertility. However, more comprehensive and longitudinal human studies are required to examine their relationship to male and female reproductive functions.
An issue of endometrial hyperplastic processes in the reproductive period is one of the pressing problems of gynecology due to their high prevalence in this age group. The continuing interest in this issue is determined by the data that endometrial hyperplastic processes tend to have a long, relapsing course, the lack of specific, pathognomonic symptoms as well as the complexity in differential diagnosis and choice of methods for prevention and treatment. Unfortunately, the problem of treating such patients remains far from being solved, which dictates a need to optimize patient management tactics, which should be aimed not only at creating proper integrated approaches to predicting development and recurrence of endometrial hyperplastic processes, but also developing a differentiated approach to management patients with this pathology in order to reduce gynecological and oncological morbidity as well as increase reproductive potential in this patient cohort.
Introduction. The tumor microenvironment (TME) consisting of non-tumor cells and other components plays a crucial role in cancer development by promoting uncontrolled tumor growth.
Aim: to detail all the components in TME and their contribution to carcinogenesis by analyzing available publications.
Results. Currently, TME study is of great interest in the medical field. Its crucial role in the tumor initiation, progression, and spreading is emphasized. Several constituents have been identified in TME including cancer-associated fibroblasts, neutrophils, adipocytes, tumor vasculature, lymphocytes, extracellular matrix, dendritic cells, neutrophil extracellular traps, etc. Thromboinflammatory reactions are also considered an important TME element.
Conclusion. TME constituents can serve as new targets for both diagnostics and antitumor therapy.
LECTURE
Understanding the mechanisms by which environmental factors impact reproductive health is crucial for informing public health interventions and policy decisions. By elucidating the pathways through which environmental stressors exert their effects, we can develop targeted strategies to mitigate risks and promote reproductive well-being. In this lecture, we will delve into the latest research findings and emerging trends in the field of environmental reproductive health. By exploring the intricate interplay between environmental exposures and reproductive outcomes, we aim to broaden our understanding of this complex relationship and its implications for human health. Through collaborative efforts across disciplines, we can work towards safeguarding reproductive health for current and future generations.
HISTORIC CASES
Over entire life, Georgios Nikolaou Papanikolaou studied cytology of the female reproductive system. Owing to Dr. Papanikolaou’s
efforts, the Pap test was created, which is relevant in diagnostics of early stage cervical cancer even today.
Here, we discuss hallmark historical events occurred while investigating antiphospholipid syndrome (APS) particularly describing how lupus anticoagulant was discovered and how scientists around the world came to define APS. The prospects for exploring APS at the present time by applying current APS criteria are considered. The contribution of Russian scientists to APS study and catastrophic APS is outlined.
SPECIAL PROJECT
Aim: to assess effectiveness and safety of a combination phytoestrogen-based product “Femo-Klim” in treatment of moderate climacteric disorders in gynecological cancer patients.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
ISSN 2500-3194 (Online)