Chemotherapy resistance of ovarian cancer, regarded as the most lethal malignant gynecological disease, can be explained by several mechanisms, including increased activity of efflux transporters leading to decreased intracellular drug accumulation, increased efflux of the therapeutic agents from the cell by multidrug-resistance-associated protein (MRP1), enhanced DNA repair, altered apoptotic pathways, silencing of a number of genes, as well as drug inactivation, especially by glutathione transferase P1 (GSTP1). Indeed, GSTP1 has been recognized as the major enzyme responsible for the conversion of drugs most commonly used to treat metastatic ovarian cancer into less effective forms. Furthermore, GSTP1 may even be responsible for chemoresistance of non-GST substrate drugs by mechanisms such as interaction with efflux transporters or different signaling molecules involved in regulation of apoptosis. Recently, microRNAs (miRNAs) have been identified as important gene regulators in ovarian cancer, which are able to target GST-mediated drug metabolism in order to regulate drug resistance. So far, miR-186 and miR-133b have been associated with reduced ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GSTP1 and MDR1. Unfortunately, sometimes miRNAs might even enhance the drug resistance in ovarian cancer, as shown for miR-130b. Therefore, chemoresistance in ovarian cancer treatment represents a very complex process, but strategies that influence GSTP1 expression in ovarian cancer as a therapeutic target, as well as miRNAs affecting GSTP1 expression, seem to represent promising predictors of chemotherapeutic response in ovarian cancer, while at the same time represent potential targets to overcome chemoresistance in the future.

The objective of this study was to measure the different redox biomarker levels within the follicular fluid (FF) and evaluate correlations with embryo quality using the one follicle–one oocyte/embryo approach. The prospective study included 54 women (average age 34.6 ± 3.0 years). Out of the 235 mature metaphase II cells that underwent intracytoplasmic sperm injection, fertilization was achieved in 177 cells, producing 92 Grade I embryos, 26 Grade II embryos, 39 Grade III embryos, and 20 Grade IV embryos. The activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione transferase were significantly higher in the group consisting of lower-quality (Grades II–IV) embryos in comparison with top-quality (Grade I) embryos (p = 0.011; p = 0.021; p = 0.008, respectively). The concentration of oxidative stress markers, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and thiol groups was significantly increased in the group with lower-quality embryos (Grades II–IV) compared to top-quality embryos (0.027; 0.018; 0.021, respectively). Furthermore, a significant positive correlation between each oxidative marker and the activities of antioxidant enzymes was observed (p < 0.001). According to our findings, the best embryos and, consequently, better in vitro fertilization outcomes are linked to low levels of oxidative stress and low antioxidant enzyme activity.

The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in cancer, including OC. Furthermore, GSTs are mostly encoded by highly polymorphic genes, which further highlights their potential role in OC, known to originate from accumulated genetic changes. Since the potential relevance of genetic variations in omega-class GSTs (GSTO1 and GSTO2), with somewhat different activities such as thioltransferase and dehydroascorbate reductase activity, has not been clarified as yet in terms of susceptibility to OC, we aimed to investigate whether the presence of different GSTO1 and GSTO2 genetic variants, individually or combined, might represent determinants of risk for OC development. Genotyping was performed in 110 OC patients and 129 matched controls using a PCR-based assay for genotyping single nucleotide polymorphisms. The results of our study show that homozygous carriers of the GSTO2 variant G allele are at an increased risk of OC development in comparison to the carriers of the referent genotype (OR1 = 2.16, 95% CI: 0.88–5.26, p = 0.08; OR2 = 2.49, 95% CI: 0.93–6.61, p = 0.06). Furthermore, individuals with GST omega haplotype H2, meaning the concomitant presence of the GSTO1*A and GSTO2*G alleles, are more susceptible to OC development, while carriers of the H4 (*A*A) haplotype exhibited lower risk of OC when crude and adjusted haplotype analysis was performed (OR1 = 0.29; 95% CI: 0.12–0.70; p = 0.007 and OR2 = 0.27; 95% CI: 0.11–0.67; p = 0.0054). Overall, our results suggest that GSTO locus variants may confer OC risk.

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INTRODUCTION: Health literacy is a cornerstone of prevention, while sex specific prevention of cardiovascular disease, a leading cause of death of women worldwide, remains less addressed and is still more a matter of local cultural habits than guideline-directed management. METHODS: A validated multiple-choice questionnaire (MCQ) designed to both educate patients and help the healthcare team learn about their traditional and sex specific modern risk factors (RF) management, including opting for comprehensive personalized long term follow up (FU) was offered to all in-patients. RESULTS: Out of 130 patients hospitalized at our department (Jan 1, 2024 - Feb 24, 2024) who were offered to fill in the MCQ, 37.7% accepted to do so, while 11.5% were excluded on ethical grounds. Women (49%) were older than men, had a more significant burden of traditional RF and possessed higher levels of knowledge and interest in RFs of both sexes, while men - especially those who declined to participate without a clear reason - even stated having no interest in their female relatives' risk profiles. Men, unlike women, showed no particular interest in a personalized and tech-savvy options of FU, although they equally use hand-held devices. CONCLUSION: These results confirm the findings obtained from a similar study conducted on an all-female sample in the same setting a year ago. However, results in men were surprising for the hostility exhibited towards junior and mid-career women which was absent when approached by a senior male member of the healthcare team. This confirms that misogyny needs to be actively suppressed.

Ovarian cancer is the deadliest form of gynecological malignancy. The presence of non-specific symptoms, together with the identification of the disease in an advanced stage, are the primary determinants of an unfavorable prognosis, resulting in an overall five-year survival rate of 45%. Currently, the treatment of choice for ovarian cancer is surgery aimed at completely removing the illness macroscopically, along with adjuvant chemotherapy. The significance of early diagnosis is evident in the several conducted prospective studies, which have not identified a successful method for early identification of this disease. Oxidative stress (OS) is a well-established contributor to carcinogenesis in several types of malignancies. It occurs when there is an imbalance between the production and clearance of reactive oxygen species. These molecules affect both pathological and physiological processes. Literature findings indicate that oxidative stress has a role in the development and pathophysiology of ovarian cancer by affecting the following four areas of cellular functioning: (i) genetic alterations, (ii) signaling pathways, (iii) transcription factors, and (iv) tumor microenvironment. Reactive oxygen species can induce mutations, which initiate the formation, proliferation, and maturation of tumor tissue. Also, prolonged elevation of the concentration of free radicals harmfully affects cells, causing the initiation of apoptotic pathways. Specifically, the presence of free radicals leads to the impairment of biomolecules and the creation of byproducts from this interaction. Consequently, these compounds may be found in various body structures and products such as tissue, plasma, urine, and other, where they can be detected. The study aims to enhance the readers' understanding of the pathogenesis of ovarian cancer, which is characterized by its undetermined cause and diverse nature. Previous research has primarily focused on surgical or medicamentous treatment, therefore the present study aims to shed light on the role of oxidative stress in this process.