Ovarian cancer (OC) remains one of the most lethal gynaecological malignancies, which is mainly due to late diagnosis, high frequency of metastasis, and the risk of developing resistance to systemic therapy. In recent years, exosomes-small extracellular vesicles (EVs) secreted by cancer cells and components of the tumour microenvironment (TME)-have been identified as potential mediators of OC progression. Exosomes participate in intercellular communication and enable the transfer of RNA, proteins, and lipids. These vesicles may modulate the immune response, promote angiogenesis, remodel the extracellular matrix, and drive epithelial-mesenchymal transitions. Exosomes also appear to play a role in the development of drug resistance via direct transfer of resistance factors or indirect modification of TME. In this review article, we summarise current knowledge on the biological role of exosomes in OC pathogenesis. We also discuss their possible diagnostic, prognostic, and therapeutic relevance. The properties and composition of exosomes make them promising noninvasive liquid biomarkers and convenient carriers for anticancer drugs. However, to fully exploit their potential, further large-scale preclinical and clinical studies are required, which should focus primarily on standardising research methods and assessing the safety and efficacy of exosome-based diagnostic and therapeutic methods.

OBJECTIVES:Irisin is an adipomyokine that has an inhibitory effect on inflammation and possesses anticancer activity. It inhibits cancer cell proliferation, metastasis, and invasion through various signaling pathways associated with carcinogenesis. It has been described to be associated with a number of malignancies in various locations. It has been recognized that it may be a biomarker and prognostic factor in some malignancies. In addition, studies indicate irisin's possible role in treating malignant lesions. MATERIAL AND METHODS:In material including 129 cases of endometrial cancer and normal endometrium in a control group of 18 women with uterine myomas. RESULTS:There were no statistical differences in irisin protein expression. There were also no differences in irisin expression according to clinical stage, type, and histopathological differentiation. CONCLUSIONS:Further clinical studies are needed to evaluate irisin activity in endometrial cancer.

Tea is a significant source of flavonoids in the diet. Due to different production processes, the amount of bioactive compounds in unfermented (green) and (semi-)fermented tea differs. Importantly, green tea has a similar composition of phenolic compounds to fresh, unprocessed tea leaves. It consists primarily of monomeric flavan-3-ols, known as catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Thanks to its antioxidant, antiproliferative, and antiangiogenic properties, EGCG has attracted the scientific community’s attention to its potential use in preventing and/or combating cancer. In this review article, we summarize the literature reports found in the Google Scholar and PubMed databases on the anticancer effect of EGCG on selected malignant neoplasms in women, i.e., breast, cervical, endometrial, and ovarian cancers, which have been published over the last two decades. It needs to be emphasized that EGCG concentrations reported as effective against cancer cells are typically higher than those found in plasma after polyphenol administration. Moreover, the low bioavailability and absorption of EGCG appear to be the main reasons for the differences in the effects between in vitro and in vivo studies. In this context, we also decided to look at possible solutions to these problems, consisting of combining the polyphenol with other bioactive components or using nanotechnology. Despite the promising results of the studies conducted so far, mainly in vitro and on animal models, there is no doubt that further, broad-based activities are necessary to unequivocally assess the potential use of EGCG in oncological treatment to combat cancer in women.

Uterine fibroids are benign tumors that occur in a large proportion of women and interfere with the proper functioning of this organ. One of the factors leading to these proliferative changes appears to be the appearance of extracellular matrix (ECM) fibrosis at the site of local inflammatory foci. Due to the potential impact of cytokines in this process, it is interesting to determine their expression levels in fibroids and surrounding tissues, which may contribute to a better understanding of the mechanisms leading to the formation of these tumors. In tissue material from 50 women with uterine fibroids who underwent hysterectomy and 45 women operated on for other reasons (most often prolapse of the reproductive organ), the concentration of inflammatory cytokines IL-1β and IL-6 and the concentration of the transcription nuclear factor NF-κβ were determined. The tissue from the fibroid, the peripheral myometrium, and the unchanged myometrium were examined in women who underwent surgery for reasons other than uterine fibroids. A significant decrease in IL-1β levels was observed in the center of the fibroid compared to both peripheral and control muscle tissue (p=0.001). The concentrations of IL-6 were found to be similar across all three locations examined. The NF-κβ levels were significantly lower in the fibroid and peripheral tissues (p<0.001) compared to the control group. The concentration of IL-1β was found to be significantly and positively correlated with the concentration of NF-κβ in uterine fibroids.

OBJECTIVES:This article aimed to systematically review the literature on smooth muscle tumors of uncertain malignant potential, known as STUMPs. These tumors pose both diagnostic and therapeutic challenges. MATERIAL AND METHODS:A literature search was conducted in PubMed using the keyword STUMP, covering articles from the last 5 years. Relevant articles were retrieved in full format and reviewed for additional references, from which further eligible articles were also included RESULTS: STUMPs often resemble leiomyomas or leiomyosarcomas. While they typically have a benign course, some patients may experience recurrence and distant metastasis. There are no standardized guidelines for treatment; however, hysterectomy is commonly performed, or myomectomy may be considered to preserve fertility. CONCLUSIONS:The findings highlight the necessity for additional studies to standardize the diagnosis and treatment of these tumors. Continuous monitoring of patients post-surgery is essential to identify any recurrence or metastasis.

OBJECTIVE:We aimed to compare MLH1 and MSH2 protein expression and Mismatch repair (MMR) status with clinical data: diagnosis, grading, and staging. Moreover, we wanted to assess any correlation between two immunohistochemical assessments: classic microscopic and computer analysis performed by a calibrated program. MATERIALS AND METHODS:Our studies were conducted on 95 cases of endometrial cancer. For each, we performed H+E staining and immunohistochemistry (IHC) of two MMR status proteins: MLH1 and MSH2. Two independent researchers assessed IHC on a 0 to ++++ scale. We classified cases as MMR-deficient based on the microscopic assessment of the absence of expression of at least one protein. For computer analysis, we used Olympus cellSens software to measure the positive IHC reaction area in µm2 in five fields of vision. RESULTS:Despite using two different assessment methods, we did not identify any statistically significant relationship between diagnosis, grading, staging, MMR protein expression, and MMR status. However, we found a strong correlation between computer analysis and semi-quantitative microscopic assessment (r=0.59 for MLH1 and r=0.76 for MSH2; p<0.001 for both). Furthermore, we revealed that computer measurement of the expression area could be a good objective prediction test for microscopic analysis (p<0.001). CONCLUSION:We did not find a relationship between MMR status and grading, staging, or diagnosis. However, we present a novel approach to immunohistochemical assessment using computer analysis. It allows us to carry out more objective and accurate studies with the IHC method.

Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women’s quality of life. The chronic nature of the disease and its recurrence are the main reasons for the search for new, non-hormonal drugs and drug candidates, either as adjunct treatment options or alternative therapies. The catechin found in green tea, epigallocatechin gallate (EGCG), has been shown to exhibit a wide array of biological activities, which may also contribute to its potential effectiveness in treating endometriosis. The poor physicochemical stability and relatively low bioavailability of EGCG have stimulated the development of a peracetylated prodrug (pro-EGCG) and other solutions, based on nanotechnology, that would eliminate the problems with EGCG. In this review article, we summarize the studies on the effects of EGCG, pro-EGCG, and EGCG-based nanoparticles on the course of endometriosis published in the GoogleScholar and PubMed databases. Of note is the fact that the results of in vitro and animal model studies have suggested that EGCG and pro-EGCG can reduce the number of endometriosis foci and their size and volume, and they can prevent fibrosis by affecting multiple molecular factors and signaling pathways. The promising results provide a basis for using green herbal extracts for endometriosis treatment in a clinical trial. Nevertheless, it should be emphasized that the number of studies on the topic is currently very limited; further expansion in the coming years is necessary. Broad, well-designed clinical trials are also essential to validate the true potential of EGCG and related compounds in the fight against endometriosis.

Treatment options for uterine myomas - the most commonly occurring benign tumors of the female reproductive organs - are varied and include pharmacological therapies, radiological management, as well as surgery. The choice of treatment option should take effectiveness and safety into account, whilst considering also the expectations of the individual patient, e.g., the desire to preserve the uterus irrespective of reproductive goals. Advances in the pathophysiology of myomas have led to the search for new therapies that fulfil these criteria. EGCG - catechin is the primary bioactive polyphenol present in green tea (Camellia sinensis). It inhibits the cell proliferation of malignant and benign tumors and induces apoptosis in tumor cells. ECGC has been shown to inhibit myoma growth in vitro and in vivo, as well as in clinical trials. A multicentre prospective FRIEND study involving 200 women with uterine myomas is currently underway. EGCG appears to be a promising, non-invasive, safe option for the treatment of uterine myomas as well as the symptoms associated with their presence: heavy menstrual bleeding, pain, and fertility disorders. Several clinical trials combining EGCG with vitamin D and B vitamins are ongoing. Recently published results have shown the safety of this therapy and a positive effect on reducing fibroid size and treating resulting ailments. Our goal is to summarize current knowledge regarding the effectiveness of EGCG in treating fibroids and the possible mechanisms of its action.

Ferulic acid (FA) is a polyphenol that is found in plants and fruits. It has a wide range of anticancer properties, including participating in cell apoptosis, inhibiting invasion and angiogenesis, and acting synergistically with standard cytostatic agents in malignant tumors. A range of molecular mechanisms are involved in anticancer activity and include the following ones: activation of cell-cycle-related proteins and enzymes such as p53, p21, Bax, and pro-caspases 3 and 9, reduction of cyclin D1 and E, proapoptotic Bcl-2, MMP-9, and NF-kV, which decrease VEGF, leading to cell cycle arrest at G0/G1 phase and death of cancer cells. Other mechanisms inhibit several pathways: PI3K/AKT/mTOR, Notch, and Wnt, which are associated with downregulation of proliferation, invasion, metastasis, and angiogenesis. FA can induce activation of ROS, leading to DNA damage in cancer cells. In vitro and in vivo studies have demonstrated the significant antitumor activity of FA in breast cancer, particularly when used in combination with cytostatic agents. In vitro studies on cervical cancer cell lines have reported similar anticancer activity of FA. This includes inhibition of cell proliferation and induction of apoptosis by downregulating antiapoptotic proteins. A case-control study conducted in Italy found that men with histologically confirmed prostate cancer had notably lower levels of FA compared to controls. Molecular in vitro studies have suggested that FA may have various effects on the signaling pathways linked to a reduction in the risk of prostate cancer, and it may act in synergy with δ-tocotrienol, which is a derivative of vitamin E. In vivo and in vitro studies on colorectal cancer have demonstrated the effects of FA on the early development of this cancer—inhibition of abnormal crypt foci (ACF-aberrant crypt foci), as well as the reduction in cancer cell viability and apoptosis through molecular changes, mainly a decrease in EGFR expression. The poor water solubility of FA makes it an attractive candidate for use as nanoparticles.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

Coffee consumption is a key aspect of modern lifestyle. Caffeine, the major component of coffee, has an impact on various human tissues and organs after being absorbed in the gastrointestinal tract. Its beneficial effects on reducing both the incidence of many diseases, including cancer, and overall mortality has been described. According to most cohort studies, coffee has a positive impact on cardiovascular diseases as it lowers the risk of cardiovascular diseases and does not increase blood pressure. Meta-analyses suggest a protective effect of caffeine contained in coffee on neurological disorders such as migraines, dementia, and slowing the progression of Alzheimer’s disease and Parkinson’s disease. However, research on malignant tumour development in humans is inconsistent. On the one hand, caffeine contained in coffee has been shown to significantly reduce the risk of breast cancer, endometrial cancer and prostate cancer. On the other hand, most meta-analyses have shown an association between coffee intake and an increased prevalence of lung cancer. In some cases, it can even lead to significant rise in morbidity. The positive impact of chlorogenic acid (a polyphenol in coffee) administered with doxorubicin has been described in in vitro and in vivo lung cancer studies.

BACKGROUND:SERPINA3 (α-1-antichymotrypsin, AACT, ACT) is produced by the liver and released into plasma in an anti-inflammatory response and plays a role as a modulator of extracellular matrix (ECM) by inhibiting serine proteases. Numerous studies proved an increased level of SERPINA3 in many types of cancer, which could be linked to SERPINA3's anti-apoptotic function. AIM:In the context of progressive ECM fibrosis during the development of uterine fibroids, which are one of the most common hypertrophic changes within the uterus, it is interesting to describe the level of SERPINA3 protein in this type of lesion and the surrounding tissues. METHODS:We used immunohistochemical staining of the SERPINA3 protein and compared the intensity of the signal between the myoma tissue and the surrounding normal tissue. RESULTS:We showed a surprising reduction in the amount of the SERPINA3 protein within uterine fibroids compared to surrounding tissues. CONCLUSION:This observation sheds new light on the role of this protein in the formation of proliferative changes and suggests that understanding the mechanism of its action may become the basis for the development of new diagnostic and therapeutic tools.

Endometrial cancer (EC) is one of the most common types of cancer in Poland and worldwide. Many risk factors lead to the pathogenesis of this disease, such as lifestyle choices, BMI, the medicines used in breast cancer therapy, and Lynch syndrome. EC cells show the expression of estrogen receptors (ERs) and progesterone receptors (PgR). These receptors occur in multiple isoforms and have a significant influence on the operation of cells. The loss of ER and PgR expression is associated with a poor prognosis. We assessed tissue slides that were obtained from 103 women with EC diagnoses of various grades, stages, and histological types. In this study, we used computer image analyses to increase the objectivity of the assessment. We proved that, in the tissue of patients with high-grade (G3) EC, the expression of PgR is significantly lower than that in the tissues of patients with low-grade EC. We also observed that PgR is significantly expressed in EC with a low FIGO stage and in the endometroid type of EC (which rarely becomes malignant compared to serous type). The expression of ERb1 was lower in patients with EC at the IV FIGO stage than in patients with stage III EC. These findings confirm that the loss of ER and PgR expression is connected with a poor prognosis.

Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.

Despite advances in surgical treatment techniques and chemotherapy-including anti-angiogenic and immune poly (ADP-ribose) polymerase inhibitors, the 5-year survival rate in ovarian cancer (OC) remains low. The reasons for this are the diagnosis of cancer in advanced clinical stages, chemoresistance and cancer recurrence. New therapeutic approaches are being developed, including the search for new biomarkers that are also targets for targeted therapy. The present review describes new molecular markers with relevance to targeted therapy, which to date have been studied only in experimental research. These include the angiogenic protein angiopoietin-2, the transmembrane glycoprotein ectonucleotide pyrophosphatase/phosphodiesterase 1, the adhesion protein E-cadherin, the TIMP metallopeptidase inhibitor 1 and Kruppel-like factor 7. Drugs affecting cancer stem cells (CSCs) in OC, such as metformin and salinomycin, as well as inhibitors of CSCs markers aldehyde dehydrogenase 1 (with the drug ATRA) and the transcription factor Nanog homeobox (microRNA) are also discussed. A new approach to prevention and possible therapies under investigation such as development of vaccines containing a subpopulation of CD117(+) and CD44(+) stem cells with a promising option for use in women with OC was described.

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time.

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, and thus represent a very unfavorable prognosis for cancer patients. The purpose of this review article is to summarize the results of studies describing the relationship between HA, the main ligand of the CD44 receptor, or other components of the HA signaling pathway. In addition, we review the course of selected female malignancies, i.e., breast, cervical, endometrial, and ovarian cancer, with the main focus on the mechanisms oriented to CD44. We also analyze reports on the beneficial use of HA-containing preparations in adjuvant therapy among patients with these types of cancer. Data from the literature suggest that HA and its family members may be critical prognostic biomarkers of selected malignancies among women. Nevertheless, the results of the available studies are inconclusive, and the actual clinical significance of HA expression analysis is still quite enigmatic. In our opinion, the HA-CD44 signaling pathway should be an attractive target for future research related to targeted therapy in gynecological cancers.

Endometriosis is a chronic disease with a complex, heterogeneous pathogenesis that affects about 10% of women of reproductive age, causing pain and leading to infertility. Treatment consists of administering pharmacological agents (resulting in a reduction of estrogen levels and inflammation), as well as the surgical removal of endometriotic lesions. Unfortunately, despite a wide range of available therapies, there is still a high recurrence rate after surgery. Consequently, it is necessary to improve the outcome of patients with endometriosis. In this context, there is growing interest in possible dietary modification to support or complement classic treatment options and even serve as a potential alternative to hormone therapy. In addition, a growing number of studies indicate positive effects of selected dietary factors on the development and course of endometriosis. This review article focuses on the potentially beneficial effects of compounds from the polyphenol group (curcumin, epigallocatechin gallate, quercetin, resveratrol), vitamins, and selected micronutrients on endometriosis. The results indicate the potential of the selected ingredients in fighting the disease. However, most of the studies have been performed on experimental animal models, with a smaller proportion looking at the actual effects of use among women. Therefore, well-designed studies are needed to assess the importance of a well-chosen diet and the effects of specific dietary factors on the health of women suffering from endometriosis.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANGPT1, CASR, and PTK2 were examined in myoma and peripheral tissues samples taken from women after myoma surgery and in normal uterine muscle tissue samples in the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANGPT1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CASR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. PTK2 expression was also lower in the myoma and periphery com-pared to healthy uterine myometrium. Calcium supplementation could have an effect on stop-ping the growth of myomas.

Colorectal cancer is a heterogenous group of neoplasms showing a variety of clinical and pathological features depending on their anatomical location. Sphingolipids are involved in the formation and progression of cancers, and their changes are an important part of the abnormalities observed during carcinogenesis. Because the course of rectal and colonic cancer differs, the aim of the study was to assess whether the sphingolipid profile is also different in tumors of these two regions. Using a combination of ultra-high-performance liquid chromatography combined with triple quadrupole mass spectrometry, differences in the amounts of cellular sphingolipids were found in colorectal cancer. Sphingosine content was higher in rectal cancer than in adjacent healthy tissue, while the content of two ceramides (C18:0-Cer and C20:0-Cer) was lower. In colon cancer, a higher content of sphingosine, sphinganine, sphingosine-1-phosphate, and two ceramides (C14:0-Cer and C24:0-Cer) was found compared to healthy tissue, but there was no decrease in the amount of any of the assessed sphingolipids. In rectal cancer, the content of sphinganine and three ceramides (C16:0-Cer, C22:0-Cer, C24:0-Cer), as well as the entire pool of ceramides, was significantly lower compared to colon cancer. The S1P/Cer ratio in rectal cancer (S1P/C18:1-Cer, S1P/C20:0-Cer, S1P/C22:0-Cer, S1P/C24:1-Cer) and in colon cancer (S1P/C18:0-Cer, S1P/C18:1-Cer, S1P/C20:0-Cer) was higher than in adjacent healthy tissue and did not differ between the two sites (rectal cancer vs. colonic cancer). It seems that the development of colorectal cancer is accompanied by complex changes in the metabolism of sphingolipids, causing not only qualitative shifts in the ceramide pool of cancer tissue but also quantitative disturbances, depending on the location of the primary tumor.