Browsing by Author "Sulaieva, Oksana"

Now showing 1 - 20 of 33

Adjusting Laboratory Practices to the Challenges of Wartime
(Narrative Inquiry in Bioethics, 2023) Sulaieva, Oksana; Shcherbakova, Anna; Dudin, Oleksandr
After 500 days of the unjust war initiated by the Russians, we look back to reflect on the challenges our medical laboratory faced during these early days. On the morning of February 24th, we were awakened by the dreadful roar of sirens, the sound of which filled us with adrenaline and anxiety. Although our team had considered the risks of Russian military aggression and thus updated our emergency plan at the beginning of 2022, the first day of the war revealed that nobody was truly ready for the bombing, air alarms, tanks on the streets of towns and cities, violence and murders of civilians. That morning the city’s transportation system collapsed, and the flow of cars cluttered all the roads as people were trying to leave the city and escape the upcoming atrocities and death. Serious and disquieted people hurried along the streets—some people rushed to shelters, and others went to the military registration and enlistment offices to fight against Russian aggressors for the life, independence, and sovereignty of Ukraine. We hurried to work, committed to performing our duties. Our medical laboratory serves more than 750 hospitals in Ukraine. Despite fear and uncertainty, we walked to the lab, taking our children and alarm case1 with documents and essential things. Months later, people asked us why we went to the laboratory instead of leaving the city or even the country. At that moment, our [End Page 155] professional duties were an anchor linking us to each other against fear and panic. Our responsibility to provide patients and physicians with the results of blood testing, pathology, and molecular reports outweighed our fears of the war. We had to complete the testing of all the samples delivered to the laboratory to provide our customers—who include children, pregnant women, diabetic and cancer patients—with data essential for identifying accurate diagnoses and effective treatments. So we spent the first days of the war in the laboratory. At the same time, we had obligations and responsibilities to our staff as well. We had to consider how to manage our employees’ protection along with continuous laboratory services provided under endless air alarms and bombings. Many healthcare facilities in eastern regions and around Kyiv were affected by missiles or completely destroyed. Of our sixty laboratory offices around Ukraine, ten were damaged or abandoned due to occupation. Several of our fleet cars were also damaged and riddled with bullets. Many employees in the regional offices in Melitopol, Kherson, Mariupol, Chernihiv, and in suburbs of Kyiv such as Bucha and Irpin lost their homes as a result of massive military operations or occupation. Dozens of our employees joined the Ukrainian armed forces to defend civilians and fight against aggressors. Many others became volunteers, involved in blood donation, medical care for the wounded, cooking, and serving the troops. And still, we had to continue our work and protect our staff at the same time. We also helped each other by sharing our goods, medication, homes, cars, warmth, and support. Some pathologists stayed at the workplace for several days moving between pathology stations, microscopes and shelters, and sleeping on the floor but continuing to work. Our main challenge was the regular terroristic attacks on healthcare facilities situated far away from the front line, which in fact, violated international humanitarian law regarding respect for human rights during armed conflicts. During the first weeks of the war, the magnitude of military aggression, massive bombing, and air attacks undermined the healthcare system and endangered laboratory staff and patients. We prioritized protective measures. Some of our laboratory staff and facilities were evacuated from Kyiv to Lviv in western Ukraine. The partial relocation of our laboratory to Lviv was also driven by the displacement of several million Ukrainians to the western part of the country.
Combined effects of probiotic and chondroprotector during osteoarthritis in rats.
(Panminerva Medica, 2020-06) Sulaieva, Oksana; Korotkyi, Oleksandr; Dvorshchenko, Kateryna; Falalyeyeva, Tetyana
Background: Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane during OA in rats. Methods: OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific). Results: It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-α expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-α expression in chondrocytes and synovial cells. Conclusions: The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.
Complementary Effect of Non-Persistent Silver Nano-Architectures and Chlorhexidine on Infected Wound Healing.
(Biomedicines, 2021-09-14) Sulaieva, Oksana; Pernakov, Mykola; Ermini, Maria Laura
Surgical site infection (SSI) substantially contributes each year to patients' morbidity and mortality, accounting for about 15% of all nosocomial infections. SSI drastically increases the rehab stint and expenses while jeopardizing health outcomes. Besides prevention, the treatment regime relies on an adequate antibiotic therapy. On the other hand, resistant bacterial strains have currently reached up to 34.3% of the total infections, and this percentage grows annually, reducing the efficacy of the common treatment schemes. Thus, new antibacterial strategies are urgently demanded. Here, we demonstrated in rats the effectiveness of non-persistent silver nano-architectures (AgNAs) in infected wound healing together with their synergistic action in combination with chlorhexidine. Besides the in vivo efficacy evaluation, we performed analysis of the bacteriological profile of purulent wound, histological evaluations, and macrophages polarization quantifications to further validate our findings and elucidate the possible mechanisms of AgNAs action on wound healing. These findings open the way for the composition of robust multifunctional nanoplatforms for the translation of safe and efficient topical treatments of SSI.
COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.
(Cancer Cytopathology, 2022-01-10) Sulaieva, Oksana; Vigliar, Elena; Pisapia, Pasquale; Iacovo, Filippo Dello
Background: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
Digital pathology implementation in cancer diagnostics: towards informed decision-making.
(Frontiers in Digital Health, 2024-05-30) Sulaieva, Oksana; Dudin, Oleksandr; Koshyk, Olena; Panko, Mariia
Digital pathology (DP) has become a part of the cancer healthcare system, creating additional value for cancer patients. DP implementation in clinical practice provides plenty of benefits but also harbors hidden ethical challenges affecting physician-patient relationships. This paper addresses the ethical obligation to transform the physician-patient relationship for informed and responsible decision-making when using artificial intelligence (AI)-based tools for cancer diagnostics. DP application allows to improve the performance of the Human-AI Team shifting focus from AI challenges towards the Augmented Human Intelligence (AHI) benefits. AHI enhances analytical sensitivity and empowers pathologists to deliver accurate diagnoses and assess predictive biomarkers for further personalized treatment of cancer patients. At the same time, patients' right to know about using AI tools, their accuracy, strengths and limitations, measures for privacy protection, acceptance of privacy concerns and legal protection defines the duty of physicians to provide the relevant information about AHI-based solutions to patients and the community for building transparency, understanding and trust, respecting patients' autonomy and empowering informed decision-making in oncology.
Ethical navigation of biobanking establishment in Ukraine: learning from the experience of developing countries.
(Journal of medical ethics, 2023-11-09) Sulaieva, Oksana; Artamonova, Oksana; Dudin, Oleksandr
Building a biobank network in developing countries is essential to foster genomic research and precision medicine for patients’ benefit. However, there are serious barriers to establishing biobanks in low-income and middle-income countries (LMICs), including Ukraine. Here, we outline key barriers and essential milestones for the successful expansion of biobanks, genomic research and personalised medicine in Ukraine, drawing from the experience of other LMICs. A lack of legal and ethical governance in conjunction with limited awareness about biobanking and community distrust are the principal threats to establishing biobanks. The experiences of LMICs suggest that Ukraine urgently needs national guidelines covering ethical and legal aspects of biospecimen-related research. National guidelines must be consistent with international ethical recommendations for safeguarding participants’ rights, welfare and privacy. Additionally, efforts to educate and engage physicians and patient communities are essential for achieving biobanking goals and benefits for precision medicine and future patients.
Fecal microbiota transplantation in patients with post-infectious irritable bowel syndrome: A randomized, clinical trial.
(Frontiers in Medicine, 2022-10-20) Sulaieva, Oksana; Tkach, Sergii; Dorofeyev, Andrii; Kuzenko, Iurii
Introduction: Research in recent years has shown the potential benefits of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS). Acute infectious gastroenteritis is a well-established risk factor for developing such forms of IBS as post-infectious IBS (PI-IBS). However, the effective use of FMT in patients with IP-IBS has not yet been clarified. Aim: The study aimed to conduct a single-center, randomized clinical trial (RCT) to assess FMT's safety, clinical and microbiological efficacy in patients with PI-IBS. Materials and methods: Patients with PI-IBS were randomized into two groups: I (standard-care, n = 29) were prescribed basic therapy, namely a low FODMAP diet, as well as Otilonium Bromide (1 tablet TID) and a multi-strain probiotic (1 capsule BID) for 1 month; II (FMT group, n = 30), each patient with PI-IBS underwent a single FMT procedure with fresh material by colonoscopy. All patients underwent bacteriological examination of feces for quantitative and qualitative microbiota composition changes. The clinical efficacy of treatment was evaluated according to the dynamics of abdominal symptoms, measured using the IBS-SSS scale, fatigue reduction (FAS scale), and a change in the quality of life (IBS-QoL scale). Results: FMT was associated with rapid onset of the effect, manifested in a significant difference between IBS-SSS points after 2 weeks of intervention (p < 0.001). In other time points (after 4 and 12 weeks) IBS-SSS did not differ significantly across both groups. Only after 3 months of treatment did their QoL exceed its initial level, as well value for 2 and 4 weeks, to a significant extent. The change in the ratio of the main microbial phenotypes in the form of an increase in the relative abundance of Firmicutes and Bacteroidetes was recorded in all patients after 4 weeks. It should be noted that these changes were significant but eventually normalized only in the group of PI-IBS patients who underwent FMT. No serious adverse reactions were noted. Conclusion: This comparative study of the results of FMT use in patients with PI-IBS demonstrated its effectiveness compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability.
From Synthesis to Clinical Trial: Novel Bioinductive Calcium Deficient HA/β-TCP Bone Grafting Nanomaterial.
(Nanomaterials (Basel), 2023-06-17) Sulaieva, Oksana; Mishchenko, Oleg; Yanovska, Anna
Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/β-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of β-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures.
Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countriesю
(Cancer Cytopathology, 2020-10-27) Sulaieva, Oksana; Vigliar, Elena; Cepurnaite, Rima; Alcaraz-Mateos, Eduardo
Background: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. Methods: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. Results: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). Conclusions: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
GLUT1 expression in patients with non-small cell lung cancer and its impact on survival.
(Reports of Morphology, 2024-12-26) Sulaieva, Oksana; Seleznov, Oleksii; Vynnychenko, Oleksandr; Moskalenko, Yuliia
GLUT1 is an essential glucose transporter, the expression of which increases in tumor cells, especially under conditions of hypoxia, and correlates with their active proliferation. This study aimed to investigate the relationship between GLUT1 expression and biological parameters and to evaluate the potential impact on survival in patients with radically treated non-small cell lung cancer (NSCLC). Forty-two patients who received radical treatment for NSCLC were involved in the study. Gender, age, smoking history, disease stage, and tumor histological type were considered when analyzing the data. GLUT1 antibodies were used to assess the degree of hypoxia. A semi-quantitative immunohistochemical score ranging from 0 to 12 was used for calculation. The chi2 and Student's t-test were used to compare categorical and parametric variables. The Cox proportional hazards model, the Kaplan-Meier method, and the Log-rank test were used to evaluate the effect of GLUT1 expression on survival. The results were considered statistically significant at p<0.05. A moderate correlation was found between GLUT1 expression and histological type of NSCLC (r=0.432, p<0.0001), sex (r=0.336, p<0.0009), and smoking (r=0.325, p<0.0009). GLUT1 overexpression was observed more in squamous cell carcinomas than in adenocarcinomas (p=0.0001). In patients with adenocarcinomas, the level of GLUT1 expression depended on age and T category. In patients with squamous cell carcinomas, GLUT1 expression was not associated with the studied clinicopathological characteristics. Patients with T1b-2a categories, without regional lymph node metastases, younger than 60, and non-smokers have better survival. Kaplan-Meier curves demonstrated no statistically significant differences in recurrence-free survival and overall survival between the patients with high and low GLUT1 (Log-rank p=0.3284 and Log-rank p=0.7161, respectively). In conclusion, GLUT1 overexpression is associated with squamous cell lung carcinomas. GLUT1 expression has no prognostic value and does not correlate with recurrence-free and overall survival in radically treated patients with NSCLC.
Hashimoto's thyroiditis attenuates progression of papillary thyroid carcinoma: deciphering immunological links
(Heliyon, 2020-01-08) Sulaieva, Oksana; Seleznov, Oleksii; Shapochka, Dmytro
Although some studies have investigated the clinicopathologic relationships between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT), there is still no clear understanding of differences in tumor immune microenvironment for PTC with coexisting HT and HT effect on PTC progression. The aim of this study was to clarify immune-mediated mechanisms of coexisting HT, which might influence PTC progression. 30 patients with histologically confirmed conventional-type PTC and 30 patients with PTC and coexisting HT were enrolled in the study. To analyze the role of immune-mediated links between PTC and HT, immunohistochemical investigation was conducted to count the number of different immune cells including T-cytotoxic cells (CD8), plasma cells (CD138), Treg cells (FOXP3), mast cells (MCT), and M2 macrophages (CD163). It was shown that despite the high number of immune cells in the intact thyroid tissues of PTC patients with coexisting HT there were no significant differences in M2 macrophages, mast cells and Treg counts inside PTC with or without HT. PTC with HT was associated with a higher number of CD8+ cells (P < 0.001) reflecting the ability of immune system to generate and recruit T-cytotoxic cells in tumor area, which can explain the protective effect of HT on PTC progression. Lymph node metastases development was associated with an increased number of mast cells, M2 macrophages and Treg along with a decreased plasma cells count regardless of coexisting HT. However, we did not find significant differences in T-cytotoxic cells quantity in node-positive and node-negative patients with or without HT, which encourages further investigation of immune escape mechanisms in PTC.
HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients.
(Scientific Reports. Nature, 2024-10-26) Sulaieva, Oksana; Matviichuk, Anton; Yerokhovych, Vikroriia
Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3-6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.
Hemostatic performance and biocompatibility of chitosan-based agents in experimental parenchymal bleeding
(Materials Science and Engineering. C, Materials for biological applications., 2020-11-21) Sulaieva, Oksana; Deineka, Volodymyr; Pernakov, Mykola
The uncontrolled parenchymatic bleeding is still a cause of serious complications in surgery and require new effective hemostatic materials. In recent years, numerous chitosan-based materials have been intensively studied for parenchymatic bleeding control but still require to increased safety and effectiveness. The current research is devoted to new hemostatic materials made of natural polymer (chitosan) developed using electrospinning and microwave-assisted methods. Hemostatic performance, biocompatibility, degradation, and in-vivo effectiveness were studied to assess functional properties of new materials. Chitosan-based agents demonstrated considerable hemostatic performance, moderate biodegradation pace and high biocompatibility in vitro. Using the electrospinning-made chitosan-copolymer significantly improved in vivo biocompatibility and degradation of Chitosan-based agents that provides opportunities for its implementation for visceral bleeding management. Chitosan aerogel could be effectively applied in hemostatic patch development due to high antibacterial activity but it is not recommended for visceral application due to moderate inflammatory effect and slow degradation.
Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma: Relation to the immune cycle.
(World Journal of Gastroenterology, 2021-08-21) Sulaieva, Oksana; Seleznov, Oleksii; Mashukov, Artem
Background: Various histological types of gastric carcinomas (GCs) differ in terms of their pathogenesis and their preexisting background, both of which could impact the tumor immune microenvironment (TIME). However, the current understanding of the immune contexture of GC is far from complete. Aim: To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept. Methods: In total, 50 GC cases were examined (15 cases of diffuse GC, 31 patients with intestinal-type GC and 4 cases of mucinous GC). The immunophenotype of GC was assessed and classified as immune desert (ID), immune excluded (IE) or inflamed (Inf) according to CD8+ cell count and spatial pattern. In addition, CD68+ and CD163+ macrophages and programmed death-ligand 1 (PD-L1) expression were estimated. Results: We found that GCs with different histological differentiation demonstrated distinct immune contexture. Most intestinal-type GCs had inflamed TIMEs rich in both CD8+ cells and macrophages. In contrast, more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+ lymphocytes but abundant CD68+ macrophages, while mucinous GC had an IE-TIME with a prevalence of CD68+ macrophages and CD8+ lymphocytes in the peritumor stroma. PD-L1 expression prevailed mostly in intestinal-type Inf-GC, with numerous CD163+ cells observed. Therefore, GCs of different histological patterns have specific mechanisms of immune escape. While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters. Conclusion: These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.
Immune Microenvironment of Muscular-Invasive Urothelial Carcinoma: The Link to Tumor Immune Cycle and Prognosis.
(Cells, 2022-05-31) Sulaieva, Oksana; Stakhovskyi, Oleksandr; Kobyliak, Nazarii
In this study, we investigated the relationship between the tumor immune microenvironment (TIME), histological differentiation and hypoxia in patients with muscular-invasive urothelial carcinomas (MIUC) after radical cystectomy. Forty-two cases of pT2-3N0M0 MIUCs underwent clinical, histological and immunohistochemical evaluation by counting CD8+, FOXP3+, CD68+, CD163+ cells and polymorphonuclear leukocytes (PMN) in intra-tumoral and peritumoral areas, assessing PD-L1 and GLUT1 expression for defining the impact of tumor immune contexture on patients' outcomes. Five-year survival rates and overall survival were calculated. Most of the MIUCs demonstrated the immune-desert or immune-excluded TIME, reflecting altered mechanisms of T-cells' activation or traffic into tumors. Tumor immune contexture was closely related to histological differentiation. CD8+ cells were scant in MIUCs with papillary and squamous differentiation, while basal-like or mesenchymal-like histological differentiation was associated with increased density of CD8+ cells. A high rate of PD-L1 expression (47.6%) was not related to immune cell infiltration. M2-macrophages predominated under CD8+ lymphocytes. The abundance of PMN and CD163+ macrophages in MIUCs was associated with high GLUT1 expression. CD8+, CD68+, FOXP3+ cells and PD-L1 status did not affect patients' outcomes, while high CD163+ density and PMN infiltration were associated with the unfavorable outcome of patients with MIUC. These data drive the hypothesis that in MIUC, immune escape mechanisms are shifted towards the role of the innate immunity cells rather than CD8+ lymphocytes' functioning.
Implementation of Molecular Profiling in the Diagnosis and Treatment Planning of Patients With Advanced Ovarian Cancer
(Proceedings of the Shevchenko Scientific Society. Medical Sciences., 2024-06-28) Sulaieva, Oksana; Hrytsay, Iryna; Mazur, Yulia; Ferneza, Severyn
Early diagnosis and personalized treatment of patients with malignant ovarian tumors based on molecular changes in the tumor of a specific patient is a priority research area in gynecological oncology. However, the clinical informativeness of certain genetic signatures remains unclear. Molecular profiling based on the next-generation sequencing (NGS) method, which allows multigenomic research of ovarian tumors, is not widely used among clinicians in routine clinical practice in Ukraine. The aim of this study was to evaluate the informativeness of molecular genetic testing using a panel that detects damage to genes of signaling pathways and the homologous recombination system (HRR) for the final diagnosis and determination of the treatment plan for patients with ovarian cancer (OC). Молекулярне профілювання на основі методу секвенування наступного покоління (NGS) дозволяє провести мультигенне дослідження раку яєчників (РЯ) та отримати цінні дані для подальшого лікування та прогнозу. Мета дослідження. Оцінити інформативність молекулярно-генетичного тестування з використанням панелі, що виявляє пошкодження генів сигнальних шляхів і системи гомологічної рекомбінації (HRR), для остаточної діагностики та визначення плану лікування пацієнток із РЯ.
In Vivo Safety of New Coating for Biodegradable Magnesium Implants.
(Materials (Basel), 2023-08-24) Sulaieva, Oksana; Dryhval, Bohdan; Husak, Yevheniia
Biodegradable Magnesium (Mg) implants are promising alternatives to permanent metallic prosthesis. To improve the biocompatibility and with the aim of degradation control, we provided Plasma Electrolytic Oxidation (PEO) of pure Mg implant in silicate-based solution with NaOH (S1 250 V) and Ca(OH)2 (S2 300 V). Despite the well-structured surface, S1 250 V implants induced enormous innate immunity reaction with the prevalence of neutrophils (MPO+) and M1-macrophages (CD68+), causing secondary alteration and massive necrosis in the peri-implant area in a week. This reaction was also accompanied by systemic changes in visceral organs affecting animals' survival after seven days of the experiment. In contrast, S2 300 V implantation was associated with focal lymphohistiocytic infiltration and granulation tissue formation, defining a more favorable outcome. This reaction was associated with the prevalence of M2-macrophages (CD163+) and high density of αSMA+ myofibroblasts, implying a resolution of inflammation and effective tissue repair at the site of the implantation. At 30 days, no remnants of S2 300 V implants were found, suggesting complete resorption with minor histological changes in peri-implant tissues. In conclusion, Ca(OH)2-contained silicate-based solution allows generating biocompatible coating reducing toxicity and immunogenicity with appropriate degradation properties that make it a promising candidate for medical applications.
Incidence of BRAF mutations in cutaneous melanoma: histopathological and molecular analysis of a Ukrainian population
(Melanoma Management, 2023-12-21) Sulaieva, Oksana; Dudin, Oleksandr; Minster, Ozar; Kobyliak, Nazarii
Aim: This study aimed to investigate the incidence of BRAF mutation in cutaneous melanoma in theUkrainian population with respect to clinical and histopathological data. Materials & methods: This single-center retrospective cohort study enrolled 299 primary CM with known BRAF status assessed by RT-PCR.Results: The overall BRAF mutation rate was 56.5% in CM and demonstrated a link with the younger age(p < 0.001), anatomical site (p < 0.001) and histological type of CM (p = 0.022). BRAF-positive CM possesseda slightly higher mitotic rate (p = 0.015) and Breslow thickness (p = 0.028) but did not relate to tumor-infiltrating lymphocytes. Conclusion: The high rate of BRAF mutations in CM patients in the Ukrainiancohort was associated with superficial spreading histology, higher depth of invasion and proliferation.
Laryngopharyngeal Reflux Alters Macrophage Polarization in Human Papilloma Virus-Negative Squamous Cell Carcinoma of the Larynx in Males.
(Clinical and Experimental Otorhinolaryngology, 2021-05) Sulaieva, Oksana; Zabolotnyi, Dmytro; Kizim, Yaroslav; Zabolotna, Diana
Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment.
(Endocrinology and metabolism (Seoul, Korea), 2020-06-24) Sulaieva, Oksana; Chernenko, Olena; Selesnov, Oleksiy
Background: The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC. Methods: Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status. Results: TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P<0.001) predominated in group 2. Immune-excluded TIME was associated with the highest LNM rate. In PTC, LNM was associated with more numerous CD163+ cells. Moreover, LNM in group 1 was associated with increased numbers of mast cells peritumorally and FOXP3+ cells intratumorally and peritumorally. Group 2 demonstrated higher STAT6 but not higher VEGF expression in tumor cells. High VEGF expression was associated with LNM regardless of HT status. Conclusion: Concomitant HT impacted PTC signaling via STAT6 and TIME by increasing the number of CD8+ cells. LNM is associated with increases in CD163+ cells and VEGF expression in PTC, whereas HT affected LNM through different mechanisms.