Svetlana Tamkovich

Radical Trachelectomy Using A Titanium-Nickelide Metal Tricotage Implant to Preserve Fertility in Cervical Cancer Patients

Among malignant neoplasms of the female reproductive system, cervical cancer traditionally occupies a leading position in terms of both morbidity and mortality. Traditional surgical treatment of early-stage cervical cancer leads to satisfactory oncological results, but irreversibly reduces the fertility in this category of patients. The aim of this work was to evaluate the applicability of a metal-ceramic implant with shape memory made of titanium nickelide for the purpose of forming uterine closure and strengthening the anastomosis zone. A total of 168 untreated patients with cervical cancer underwent radical trachelectomy with reinforcement of the utero-vaginal anastomosis using a titanium-nickelide shape memory implant. The fertility of women after organ-preserving treatment was evaluated. Thirty-nine pregnancies were registered. Currently, 28 healthy children have been born. Two patients gave birth twice, one woman gave birth to twins. In addition, 2 miscarriages were registered at 7 and 19 weeks, 7 patients terminated pregnancy for social reasons at early stages, 2 patients are currently pregnant, at 24 and 32 weeks. The median follow-up for this category of patients is 89±9.6 months. Eight relapses were registered at various follow-up periods with the localization of the relapse mainly in the area of the anastomosis and iliac vessels. Analysis of menstrual function showed that the duration of the menstrual cycle after surgical treatment in the volume of radical trachelectomy was 29±4.7 days and did not differ significantly from the indicators before the operation. The duration of menstruation also did not differ significantly before and after surgical treatment. Improvement of the method of organ-preserving surgical treatment by radical trachelectomy with the formation of the uterine locking apparatus using titanium-nickelide metal tricotage contributes to the improvement of reproductive results without compromising oncological effectiveness.

Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients

Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.