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Background: Gynecological cancers (GCs) affect the reproductive system of females, and are of multiple types depending on the affected organ most common of which are cervical, endometrial, ovarian cancers. Among different risk factors for GCs, ABO blood group system is considered as one of the pivotal contributing factors for increased susceptibility of GCs. The aim of our study was to report on the demographics of GC patients and to investigate the relationship between the ABO blood group system and the risk of acquiring GC in our population. Methods: The current retrospective cross-sectional study was carried out between the years of 2016 and 2023. The sample included all the patients having age > 18 with a record of blood group and confirmed histological or cytological diagnosis as per International Federation of Gynecology and Obstetrics (FIGO) guidelines. A comprehensive review of the charts was conducted to gather data including demographics, tumor characteristics, comorbidities, adverse effects, and treatment methods. Results: A total of 543 female patients were included in the study. The mean age of patients was 61.6. The three most common BG in our GC cases were as O + (43.8%), followed by A + (26%), and B + (15.5%). Among comorbidities, hypertension (HTN), diabetes mellitus (DM), dyslipidemia were the top three affecting GC patients. A significant association (p < 0.05) between ABO BG and serous histology in endometrial cancer was found. ABO blood group and fallopian cancer showed a significant relationship between serous histology and B blood group (p < 0.05). For ovarian cancer a significant association between AB blood group and recurrence rates were found (p < 0.05). In case of the patient dependent GCs, a significant association between ovarian cancers and recurrence, fallopian tube cancers and adverse events and survival status, vaginal/vulval cancers and TNM stage and mixed GCs and tumor type (carcinoma) was observed (P < 0.05). Furthermore, multinomial analysis between various confounding factors and GCs revealed that the risk of Cervical, Endometrial and Ovarian cancers to be significant for Type B BG (P < 0.05). Conclusion: Our study found that O + BG was the most prevalent among our population. Furthermore, there was a significant association between BG B and endometrial and serous histology in fallopian tube and between BG AB and ovarian malignancies, respectively. Additionally, multinomial analysis revealed higher risk of Cervical, Endometrial and Ovarian cancers for Type B BG (P < 0.05). [ABSTRACT FROM AUTHOR]

The vagina hosts a community of microorganisms known as the vaginal microbiota. This community is relatively stable and straightforward, with Lactobacillus species being the most dominant members. The vaginal microbiota has various functions that are essential for maintaining human health and balance. For example, it can metabolise dietary nutrients, produce growth factors, communicate with other bacteria, modulate the immune system, and prevent the invasion of harmful pathogens. When the vaginal microbiota is disrupted, it can lead to diseases and infections. The observed disturbance is distinguished by a reduction in the prevalence of Lactobacillus and a concurrent rise in the number of other bacterial species that exhibit a higher tolerance to low oxygen levels. Gynecologic cancers are a group of cancers that affect the female reproductive organs and tissues, such as the ovaries, uterus, cervix, vagina, vulva, and endometrium. These cancers are a major global health problem for women. Understanding the complex interactions between the host and the vaginal microorganisms may provide new insights into the prevention and treatment of gynecologic cancers. This could improve the quality of life and health outcomes for women. [ABSTRACT FROM AUTHOR]

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30–200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy improves survival for many cancer patients. However, some patients still refuse radiotherapy despite the recommendations of their physicians. We aimed to investigate the impact of refusing recommended radiotherapy on overall survival in patients with gynecological cancers (GC) and attempted to describe what characteristics are associated with the refusal of radiotherapy. Methods: Data were extracted from the Surveillance, Epidemiology and End Result (SEER) database for patients who were diagnosed with GC and recommended for radiotherapy between 1988 and 2016. Kaplan–Meier and multivariate Cox regression analyses were utilized to analyze the impact of refusal of radiotherapy on overall survival. Univariate and multivariate logistic regression analyses were used to identify characteristics associated with refusal of radiotherapy. Results: In total, 1,226 of 208,093 patients (0.6%) refused radiotherapy. Multivariate Cox regression analysis showed that refusal of radiotherapy was associated with poorer overall survival in GC patients with stage I/II [hazard ratio (HR) = 1.64; 95% confidence interval (CI), 1.50–1.79], but may not affect overall survival in patients with stage III/IV (HR = 1.03; 95%CI, 0.84–1.25). Multivariate logistic regression analysis demonstrated that factors such as older age (40–65 years, > 65 years), unmarried status (divorced, single, widowed), higher foreign-born rate (1.87-2.82%, 1.51–2.19), refusal of surgery (recommended but not performed), and higher grade (poorly differentiated, undifferentiated/anaplastic) may increase the likelihood of refusing radiotherapy (all P < 0.05). Factors that may reduce the likelihood of refusing radiotherapy include higher income (> 42,810$), lower grade (well-differentiated), primary site of ovarian cancer, and no/unknown chemotherapy (all P < 0.05). Conclusion: Refusal of radiotherapy is related to worse overall survival in GC patients with stage I/II, and many characteristics may affect a patient's choice of refusal of radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Revealing the impacts of endogenous and exogenous mutagenesis processes is essential for understanding the etiology of somatic genomic alterations and designing precise prognostication and treatment strategies for cancer. DNA repair deficiency is one of the main sources of endogenous mutagenesis and is increasingly recognized as a target for cancer therapeutics. The role and prevalence of mechanisms that underly different forms of DNA repair deficiencies and their interactions remain to be elucidated in gynecological malignancies.Methods: We analyzed 1231 exomes and 268 whole-genomes from three major gynecological malignancies including uterine corpus endometrial carcinoma (UCEC) as well as ovarian and cervical cancers. We also analyzed data from 134 related cell lines. We extracted and compared de novo and refitted mutational signature profiles using complementary and confirmatory approaches and performed interaction analysis to detect co-occurring and mutually exclusive signatures.Results: We found an inverse relationship between homologous recombination deficiency (HRd) and mismatch repair deficiency (MMRd). Moreover, APOBEC co-occurred with HRd but was mutually exclusive with MMRd. UCEC tumors were dominated by MMRd, yet a subset of them manifested the HRd and APOBEC signatures. Conversely, ovarian tumors were dominated by HRd, while a subset represented MMRd and APOBEC. In contrast to both, cervical tumors were dominated by APOBEC with a small subsets showing the POLE, HRd, and MMRd signatures. Although the type, prevalence, and heterogeneity of mutational signatures varied across the tumor types, the patterns of co-occurrence and exclusivity were consistently observed in all. Notably, mutational signatures in gynecological tumor cell lines reflected those detected in primary tumors.Conclusions: Taken together, these analyses indicate that application of mutation signature analysis not only advances our understanding of mutational processes and their interactions, but also it has the potential to stratify patients that could benefit from treatments available for tumors harboring distinct mutational signatures and to improve clinical decision-making for gynecological malignancies. [ABSTRACT FROM AUTHOR]

Gynecological and breast cancers are a group of heterogeneous malignant tumors. Although existing treatment strategies have ameliorated the clinical outcomes of patients, the overall survival rate of advanced diseases remains unsatisfactory. Increasing evidence has indicated that the development and prognosis of tumors are closely related to the tumor microenvironment (TME), which restricts the immune response and provokes malignant progression. Tumor-associated macrophages (TAMs) are the main component of TME and act as a key regulator in tumor metastasis, immunosuppression and therapeutic resistance. Several preclinical trials have studied potential drugs that target TAMs to achieve potent anticancer therapy. This review focuses on the various functions of TAMs and how they influence the carcinogenesis of gynecological and breast cancers through regulating cancer cell proliferation, tumor angiogenesis and tumor-related immunosuppression. Besides, we also discuss the potential application of disabling TAMs signaling as a part of cancer therapeutic strategies, as well as CAR macrophages, TAMs-based vaccines and TAMs nanobiotechnology. These research advances support that targeting TAMs combined with conventional therapy might be used as effective therapeutics for gynecological and breast cancers in the future. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer. [ABSTRACT FROM AUTHOR]

Estrogen evidently involves critically in the pathogenesis of gynaecological-cancers. Reports reveal that interference in estrogen-signalling can influence cell-cycle associated regulatory-processes in female reproductive-organs. The major determinants that influence E2-signallings are estrogen-receptor (ER), estrogen-sulfotransferase (SULT1E1), sulfatase (STS), and a formylglycine-generating-enzyme (FGE) which regulates STS activity. The purpose of this mini review was to critically analyze the correlation between oxidative-threats and redox-regulation in the process of estrogen signalling. It is extensively investigated and reported that oxidative-stress is linked to cancer. But no definite mechanism has been explored till date. The adverse effects of oxidative-threat/free-radicals (like genotoxic-effects, gene-regulation, and mitochondrial impairment) have been linked to several diseases like diabetes/cardiovascular-syndrome/stroke and cancer. However, a significant correlation between oxidative-stress and gynaecological-cancers are repeatedly reported without pointing a definite mechanism. For the first time in our study we have investigated the relationship between oxidative stress and the regulation of estrogen via estrogen metabolizing proteins. Reports reveal that ER, SULT1E1, STS and FGE are target-molecules of oxidative-stress and may function differently in oxidizing and reducing environment. In addition, estrogen itself can induce oxidative-stress. This fact necessitates identifying the critical connecting events between oxidative-stress and regulation of estrogen-associated-molecules (ER, SULT1E1, STS, and FGE) that favors tumorigenesis/carcinogenesis. The current review focus is on unique redox-regulation of estrogen and its regulatory-molecules via oxidative-stress. This mechanistic-layout may identify new therapeutic-targets and open further scopes to treat gynecological-cancers more effectively. [ABSTRACT FROM AUTHOR]