Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis.

The complex and multi-stage processes of carcinogenesis are accompanied by a number of phenomena related to the potential involvement of various chemopreventive factors, which include, among others, compounds of natural origin such as flavonols. The use of flavonols is not only promising but also a recognized strategy for cancer treatment. The chemopreventive impact of flavonols on cancer arises from their ability to act as antioxidants, impede proliferation, promote cell death, inhibit angiogenesis, and regulate the immune system through involvement in diverse forms of cellular death. So far, the molecular mechanisms underlying the regulation of apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis occurring with the participation of flavonols have remained incompletely elucidated, and the results of the studies carried out so far are ambiguous. For this reason, one of the therapeutic goals is to initiate the death of altered cells through the use of quercetin, kaempferol, myricetin, isorhamnetin, galangin, fisetin, and morin. This article offers an extensive overview of recent research on these compounds, focusing particularly on their role in combating cancer and elucidating the molecular mechanisms governing apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. Assessment of the mechanisms underlying the anticancer effects of compounds in therapy targeting various types of cell death pathways may prove useful in developing new therapeutic regimens and counteracting resistance to previously used treatments.

Selected Flavonols in Breast and Gynecological Cancer: A Systematic Review.

The consumption of foods that are rich in phenolic compounds has chemopreventive effects on many cancers, including breast cancer, ovarian cancer, and endometrial cancer. A wide spectrum of their health-promoting properties such as antioxidant, anti-inflammatory, and anticancer activities, has been demonstrated. This paper analyzes the mechanisms of the anticancer action of selected common flavonols, including kemferol, myricetin, quercetin, fisetin, galangin, isorhamnetin, and morin, in preclinical studies, with particular emphasis on in vitro studies in gynecological cancers and breast cancer. In the future, these compounds may find applications in the prevention and treatment of gynecological cancers and breast cancer, but this requires further, more advanced research.

Cancer stem cells markers in ovarian cancer: Clinical and therapeutic significance (Review).

Ovarian cancer is a gynecological neoplasm that can be found in women, which, due to diagnostic difficulties, is often detected at advanced stages when treatment becomes a significant problem. Moreover, in a number of cases there is a cancer recurrence and resistance to standard chemotherapy treatment. It has been suggested that cancer stem cells (CSCs) that were not eradicated during therapy may be responsible for this. For this reason, effective therapeutic methods eliminating CSCs are being studied, such as therapy targeting CSCs markers. In addition, numerous studies have also drawn attention to the usefulness of CSCs markers in predicting disease progression and assessing patient's prognosis as well as their importance in the development of treatment resistance. The present review presented research on selected CSCs markers, which may be of significant prognostic and therapeutic importance in ovarian cancer.

Analysis of the concentration of CXCL8 chemokine and its CXCR1 and CXCR2 receptors in peritoneal fluid of women with endometriosis.

Endometriosis is an inflammatory estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity. An important role in the pathogenesis of this disease is played by disorders of the immune system involving chemokines and their receptors, including the CXCL8-CXCR1/ 2 system. AIM: The aim of the study was to assess the concentration of the CXCL8 chemokine and its CXCR1 and CXCR2 receptors in the peritoneal fluid of women with endometriosis. MATERIALS AND METHODS: The study included 32 women aged 21 to 47 years with diagnosed endometriosis and a control group of 8 healthy women aged 21 to 40 years. The material for the research was the peritoneal fluid collected during the laparoscopic procedure. The concentration of chemokines was determined by ELISA tests. RESULTS: The conducted studies showed that the concentration of the CXCL8 chemokine was significantly higher in the peritoneal fluid of the studied women and depended on the clinical advancement of the disease. CONCLUSIONS: Changes in the concentration of the CXCL8 chemokine in the peritoneal fluid of women with endometriosis may indicate impaired immune response and indicate an inflammatory process within the peritoneal cavity. The demonstrated relationship between the concentration of CXCL8 and the stages of clinical advancement indicates a significant role of this chemokine in the development of the disease.

Analysis of CXCL8 and its receptors CXCR1/CXCR2 at the mRNA level in neoplastic tissue, as well as in serum and peritoneal fluid in patients with ovarian cance.

Understanding the relationship between the coexistence of inflammatory and neoplastic processes in ovarian cancer, particularly those involving chemokines and their receptors, may help to elucidate the involvement of the studied parameters in tumor pathogenesis and could lead to improved clinical applications. Therefore, the present study aimed to analyze the levels of C­X­C motif chemokine ligand 8 (CXCL8), and its receptors C­X­C chemokine receptor (CXCR)1 and CXCR2, in the serum and peritoneal fluid of women with ovarian cancer, and to evaluate the association between the expression of these parameters in tumor tissue and patient characteristics, particularly the degree of histological differentiation. The study group included women with ovarian cancer diagnosed with serous cystadenocarcinoma International Federation of Gynecology and Obstetrics stage IIIc and a control group, which consisted of women who were diagnosed with a benign lesion (serous cystadenoma). The transcript levels of CXCL8, CXCR1 and CXCR2 were evaluated using reverse transcription­quantitative PCR (RT­qPCR). The quantitative analysis was carried out using the LightCycler® 480 System and GoTaq® 1­Step RT­qPCR System, according to the manufacturers' instructions. The concentration of CXCL8 in serum and peritoneal fluid was determined using a Human Interleukin­8 ELISA kit, and the concentrations of CXCR1 and CXCR2 were determined using the CLOUD­CLONE ELISA kit. Local and systemic disturbances in immune and inflammatory responses involving the CXCL8 chemokine and its receptors indicated the involvement of these studied parameters in the pathogenesis of ovarian cancer. Immunoregulation of the CXCL8­CXCR1 system may influence the course of the inflammatory process accompanying ovarian cancer development, which may result in the identification of novel clinical applications; however, further studies are required.

The role of galectins­1, 3, 7, 8 and 9 as potential diagnostic and therapeutic markers in ovarian cancer (Review).

The incidence of ovarian cancer is increasing, particularly throughout the highly developed countries, while this cancer type remains a major diagnostic and therapeutic challenge. The currently poorly recognized lectins called galectins have various roles in interactions occurring in the tumor microenvironment. Galectins are involved in tumor­associated processes, including the promotion of growth, adhesion, angiogenesis and survival of tumor cells. Results of research studies performed so far point to a complex role of galectins­1, 3, ­7, ­8 and ­9 in carcinogenesis of ovarian cancer and elucidation of the mechanisms may contribute to novel forms of therapies targeting the proteins. In particular, it appears important to recognize the reasons for changes in expression of galectins. Galectins also appear to be a useful diagnostic and prognostic tool to evaluate tumor progression or the efficacy of therapies in patients with ovarian cancer, which requires further study.

Participation of Selected Soluble BMP-2 and BMP-7 Bone Morphogenetic Proteins and Their Soluble Type I ALK-1 and Type II BMPR2 Receptors in Formation and Development of Endometriosis.

Angiogenesis is considered to be one of the key stages in the development of endometriosis. Recent studies indicate that bone morphogenetic proteins (BMPs) and their receptors (BMPR) may play an important role in the angiogenesis process. In the literature, however, there is a lack of publications concerning binding BMPs and their receptors with the pathogenesis of endometriosis. The aim of the study was to determine the role of soluble bone morphogenetic proteins, BMP-2 and BMP-7, and their receptors, ALK-1 and BMPR2, in the process of the formation and development of endometriosis. Peritoneal fluid was collected in the proliferative phase of the menstrual cycle, from 80 women aged 21-49 years (mean age 31.3 ± 6.7 years) undergoing laparoscopy to determine the causes of primary infertility. The study involved 60 women in the I, II, III, and IV stages of the disease. The reference group consisted of 20 women who did not have endometriosis or other lesions in the pelvic area. The concentration in the peritoneal fluid of women with endometriosis was compared to the concentration of this parameter in the reference group, and a statistically significant reduction in the concentration of the BMP-2 molecule was found, as well as increasing concentrations of BMP-7, ALK-1, and BMPR2. BMP-2 and BMP-7 and their soluble receptors, ALK-1 and BMPR2, are involved in the formation of endometriosis. The changes in the concentrations of most of the tested parameters demonstrated in the study, especially in the early stages of the disease, may indicate the more effective formation of new blood vessels in this period.

The presence of anti-leucocyte antibodies in the plasma of convalescent women after SARS-CoV-2 infection as a reason for disqualification for plasma therapy - analysis based on a literature review.

According to the data from November 29 2020, the SARS-CoV-2 coronavirus was responsible for 61 866 635 cases of infections and 1 448 990 deaths worldwide, and the number is still growing rapidly. The main problem is the rapid increase in the number of patients with pneumonia complicated by respiratory failure. In the treatment of COVID- 19 patients, a significant effect of convalescent plasma (CP) therapy from convalescent patients with SARS-CoV-2 IgG neutralizing antibodies is indicated. After this procedure, the total duration of the infection was shortened and the clinical condition improved faster than in patients who did not receive this form of therapy. The aim of the study was to explain the cause disqualifying women with anti-leucocyte anitibodies as CP plasma donors for COVID-19 patients. However, according to the literature, 2% of patients who received plasma from convalescents developed Transfusion Related Acute Lung Injury (TRALI). The most common causes of TRALI are anti-leukocyte antibodies directed against Human Leukocyte Antigens (HLA) class I and II and against Human Neutrophil Antigens (HNA). Therefore, patients with COVID-19 may only be transfused with plasma from convalescent women with a history of pregnancy after testing negative for anti-leucocyte antibodies in the pre-plasmapheresis blood sample.