Cancers Of Reproductive System Research Articles

Reproductive system cancer in females of the Tyva Republic. Epidemiological characteristics

Background. The incidence of female reproductive system cancer, including breast, cervical, ovarian and uterine cancers, is steadily increasing, and therefore it is advisable to conduct an epidemiological analysis and assess the quality of medical care. The purpose of the study was to analyze the epidemiological characteristics of reproductive system cancer in females of the Tyva Republic. Material and Methods. The reporting forms № 7 “Cancer incidence in the Tyva Republic” for 2013–2022 were used. Age-standardized incidence rates were calculated using the “Oncostat” program, and cancer care quality was assessed using “Cancer Care Indicators” program. Results. Reproductive system cancer in the Tyva Republic accounted for 46.3 % of all malignant neoplasms in females during 2013–2022. In 2022, breast cancer was the most common cancer (16.2 %) followed by cervical cancer (13.7 %), ovarian cancer (6.7 %), and uterine cancer (4.0 %). During the study period, none of these cancers showed a statistically significant increase in agestandardized incidence rates (AS R). In 2022, age-standardized incidence rates in the Tyva Republic were higher than those in the Siberian Federal District for cervical cancer (27.5 ± 3.7 vs 16.3 ± 0.4 0/0000) and for ovarian cancer (14.1 ± 2.8 vs 12.7 ± 0.3 0/0000), but lower for breast cancer (32.4 ± 4.1 vs 58.7 ± 0.6 0/0000) and uterine cancer (8.6 ± 2.2 vs 19.7 ± 0.4 0/0000). Overall, cancer care quality indicators for reproductive system cancers had improved. Active detection increased from 22.0 to 29.8 %, p=0.039 (in the Siberian Federal District: from 27.6 to 37.2 %, p=0.001). The detection rate at I–II stages increased from 53.7 to 75.2 %, p=0.004 (in the Siberian Federal District: from 63.0 to 71.3 %, p=0.001). The percentage of advanced stages decreased from 37.4 % to 15.5 %, p=0.001 (from 27.4 % to 23.1 % in the Siberian Federal District, p=0.013). The oneyear mortality rates also decreased from 19.0 to 5.4 %, p=0.013 (in the Siberian Federal District: from 11.8 to 8.5 %, р<0.001). The high incidence of cervical cancer, the absence of noticeable optimal changes in the early detection and the high prevalence of HPV infection among the female population of the Tyva Republic indicate the relevance of mass HPV testing as a part of secondary cancer prevention. Conclusion. The high incidence of female reproductive system cancer and the current status of reproductive cancer care in the Republic of Tyva dictate the need to strengthen primary, secondary and tertiary cancer prevention.

Reproductive system cancer in females of the Tyva Republic. Epidemiological characteristics

Background. The incidence of female reproductive system cancer, including breast, cervical, ovarian and uterine cancers, is steadily increasing, and therefore it is advisable to conduct an epidemiological analysis and assess the quality of medical care. The purpose of the study was to analyze the epidemiological characteristics of reproductive system cancer in females of the Tyva Republic. Material and Methods. The reporting forms № 7 “Cancer incidence in the Tyva Republic” for 2013–2022 were used. Age-standardized incidence rates were calculated using the “Oncostat” program, and cancer care quality was assessed using “Cancer Care Indicators” program. Results. Reproductive system cancer in the Tyva Republic accounted for 46.3 % of all malignant neoplasms in females during 2013–2022. In 2022, breast cancer was the most common cancer (16.2 %) followed by cervical cancer (13.7 %), ovarian cancer (6.7 %), and uterine cancer (4.0 %). During the study period, none of these cancers showed a statistically significant increase in agestandardized incidence rates (AS R). In 2022, age-standardized incidence rates in the Tyva Republic were higher than those in the Siberian Federal District for cervical cancer (27.5 ± 3.7 vs 16.3 ± 0.4 0/0000) and for ovarian cancer (14.1 ± 2.8 vs 12.7 ± 0.3 0/0000), but lower for breast cancer (32.4 ± 4.1 vs 58.7 ± 0.6 0/0000) and uterine cancer (8.6 ± 2.2 vs 19.7 ± 0.4 0/0000). Overall, cancer care quality indicators for reproductive system cancers had improved. Active detection increased from 22.0 to 29.8 %, p=0.039 (in the Siberian Federal District: from 27.6 to 37.2 %, p=0.001). The detection rate at I–II stages increased from 53.7 to 75.2 %, p=0.004 (in the Siberian Federal District: from 63.0 to 71.3 %, p=0.001). The percentage of advanced stages decreased from 37.4 % to 15.5 %, p=0.001 (from 27.4 % to 23.1 % in the Siberian Federal District, p=0.013). The oneyear mortality rates also decreased from 19.0 to 5.4 %, p=0.013 (in the Siberian Federal District: from 11.8 to 8.5 %, р<0.001). The high incidence of cervical cancer, the absence of noticeable optimal changes in the early detection and the high prevalence of HPV infection among the female population of the Tyva Republic indicate the relevance of mass HPV testing as a part of secondary cancer prevention. Conclusion. The high incidence of female reproductive system cancer and the current status of reproductive cancer care in the Republic of Tyva dictate the need to strengthen primary, secondary and tertiary cancer prevention.

Time to treatment start as a survival predictor for reproductive system cancer: a population-based study

Objective: To evaluate the effect of the time from morphological confirmation of the diagnosis to the start of specialized treatment (time to treatment start: TTS) on cancer-specific survival (CSS) of patients with cancer of the female reproductive system (CFRS) using the data from the regional cancer registry of the Arkhangelsk region (ARCR) over the period 2000 to 2022. Material and methods. depersonalized data on all cases of breast (BC), cervical (CC), corpus uteri (CUC) and ovarian (OC) cancers were obtained from the ARCR for the period 2000–2022. We compared survival with TTS of 0–7 days (recommended by the state guarantee program), 2–4, 5–8, 9–12 weeks, and 3–6, 7–12 months. Cancer-specific survival was calculated using the life tables and Kaplan-Meier methods. The Cox proportional hazard model was used to correct for other prognostic factors. Results. A total of 19321 cases were analyzed. The ministerial recommended TTS of ≤7 days was observed in 61.9 %, 28.5 %, 27.3 % and 55.9 % of patients with BC, CC, CUC and OC, respectively. the five-year CSS for BC, CC, CUC and OC was 73.9 %, 66.5 %, 73.0 % and 52.1 %, respectively. The TTS of ≤7 days compared to longer TTS was associated with the highest 5-year CSS rate in breast cancer (74.3 vs 45–4-67.0 %) and CC (80.2 vs 63.1–75.0 %); no significant differences were found in CUC and OC. The risk of death from CFRS was the same for TTS of ≤2 months in breast cancer and ≤12 months in other CFRS. Conclusion. Clinical practice shows that the time before the start of special treatment in accordance to state guarantees may be insufficient. early treatment initiation is often possible in the early stages of CFRS. The time to treatment start of < 8 weeks after morphological verification does not worsen survival. The identification of individual groups of patients who need earlier treatment is warranted.

MiRNA-202 Role in Reproductive System and Gynecological Cancers

MiRNA-202 Role in Reproductive System and Gynecological Cancers

Abstract LB318: Exploring early precursor lesions of ovarian cancer: Insights from an in vitro model

Abstract Ovarian cancer ranks as the fifth leading cause of cancer-related deaths in women, surpassing other cancers of the female reproductive system. Recent epidemiological and molecular studies highlight the significance of high-grade serous carcinoma (HGSC), the most aggressive subtype of ovarian cancer, constituting nearly 96% of cases with mutations in p53. HGSC originates from fallopian tube secretory epithelial (FTSEC) cells through a progression of precursor lesions, ranging from p53 signatures to serous tubal intraepithelial carcinoma (STIC). The p53 signature involves a linear expansion of over 12 TP53 mutant FTSECs, morphologically normal and displaying no increase in proliferative activity. In this study, we established a model system for P53 signature by either overexpressing p53 mutations (R175H and R273H) or knocking down P53 expression in normal FTSECs maintained as 2D, 3D, or organoid cultures. We have characterized the cells using RNA seq, mass spectroscopy and functional assays. Functional assays revealed increased migration and proliferation, along with decreased apoptosis in response to the cytotoxic stimulus (cisplatin). Despite the inability of p53 signature cells to proliferate or migrate in vivo, our hypothesis posited that clonal expansion of progenitor cell with a p53 mutation maintains plasticity by preserving the stemness of one or more cells capable of responding to cues from the microenvironment. Our experiments revealed heterogeneity in the model system, reflecting the composition of p53 signature in vivo. We also observed that stem-like cells tend to organize into clusters. Notably, stem-like cluster cells bearing a p53 signature exhibit migratory behavior, whereas clusters lacking p53 do not demonstrate such mobility. Given that most high-grade serous carcinoma (HGSC) cases occur in postmenopausal women, we demonstrated induction of proliferation and migration of p53 mutant stem cells in response to stimuli from aging stromal cells (fibroblasts and autologous immune cells) and to changes in hormonal background in our model. Conclusion: This study illuminates a novel aspect of ovarian cancer development, underscoring the role of a distinct population of fallopian tube epithelial cells with stem-like properties within p53 signatures. Further investigations into the tumorigenicity of these cells hold promise for providing valuable insights into future therapeutic strategies. Citation Format: Yan E. Wang, Vera Levina, Deborah L. Galson, Anna E. Lokshin. Exploring early precursor lesions of ovarian cancer: Insights from an in vitro model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB318.

Abstract PR-006: A novel bispecific NK cell engager targeting FSHR and Siglec-7 displays potent anti-tumor immunity against ovarian cancer

Abstract Ovarian cancer (OC) is the deadliest gynecologic malignancy, with the highest mortality among cancers of the female reproductive system. Because of the close interaction between the OC cells and tumor microenvironment (TME), development of approaches which not only target tumor cells but also can maintain their anti-tumor function in this TME is of high importance. Uniquely, Follicle stimulating hormone receptor (FSHR) represents such an important target with specificity for OC and ovarian granulosa cells. We have recently developed monoclonal antibodies (mAbs) that specifically recognize human FSHR on the surface of multiple OC. We characterized them, selected potent anti-FSHR mAb: D2AP11 for detailed investigation and immune engineering in the form of a bispecific T cell engager (D2AP11-TCE) (Bordoloi et al., JCI Insight, 2022). Since most OCs are extremely aggressive and have restricted treatment choices, engaging additional immune effector components may further help. We have developed mAbs against PAN NK marker; Siglec 7 in humanized mice. We identified several Siglec-7 mAbs through high throughput screening and down-selected the pertinent clones. By using a highly potent anti-Siglec-7 clone DB7.2, we have developed a novel NK cell engager (NKCE): DB7.2xD2AP11 NKCE, by linking two antibody binding fragments (scFVs) arranged to bind FSHR, the OC antigen and hman Siglec-7, the NK marker. The NKCE was efficiently expressed in vitro and showed potent binding to both FSHR overexpressing K562 cells as well as Siglec-7 overexpressed HEK293T cells. This novel NKCE resulted in robust and specific killing of multiple OC targets in vitro in the presence of human PBMCs or NK cells, from multiple donors. The OC targets evaluated for killing by the NKCE include high grade serous adenocarcinoma, ovarian clear cell adenocarcinoma and ovarian cystadenocarcinoma lines which carry different mutations; BRCA1&2, AKT, TP53, PIK3CA, BRAF etc. and exhibit resistance against a wide array of cancer drug targets; PARP, HSP90, HDAC, MTORC, DNA alkylating agents, EGFR, PI3K, and WEE1, among others. DB7.2xD2AP11 NKCE displayed killing with EC50-142.87 pM and 236.6 pM against target OVISE-FSHR and OVCAR3 cells respectively, indicating its potency. Further, DNA encoded DB7.2xD2AP11 NKCE significantly attenuated the tumor burden in OVCAR3-FSHR and OVISE challenged humanized mice model. Additionally, this novel NKCE significantly enhanced the median survival of OVCAR3-FSHR challenged mice, suggesting in vivo potency. These data support further research on this novel NKCE as crucial tools for treating OC as well as targeted therapies for other malignancies. Of note, it is the first study of the development of Siglec-7 or any Siglec family member as a bispecific immune engager for targeted immunotherapy. Citation Format: Devivasha Bordoloi, Abhijeet J. Kulkarni, Opeyemi S. Adeniji, Pratik S. Bhojnagarwala, Shushu Zhao, Candice Ionescu, Mohamed bdel-Mohsen, David B. Weiner. A novel bispecific NK cell engager targeting FSHR and Siglec-7 displays potent anti-tumor immunity against ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-006.

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases-Focus on Epigenetic Mechanisms.

The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, and polycystic ovary syndrome (PCOS), which are widespread benign health problems causing troublesome and painful symptoms and significantly impairing the quality of life of affected women, and they are some of the main causes of infertility. In addition to the available surgical and pharmacological options, the effects of supporting standard treatment with naturally occurring compounds, mainly polyphenols, are being studied. Catechins are responsible for the majority of potential health benefits attributed to green tea consumption. Epigallocatechin gallate (EGCG) is considered a non-toxic, natural compound with potential anticancer properties. Antioxidant action is its most common function, but attention is also drawn to its participation in cell division inhibition, apoptosis stimulation and epigenetic regulation. In this narrative review, we describe the role of EGCG consumption in preventing the development of benign reproductive disorders such as UF, endometriosis, and PCOS, as well as malignant gynecologic conditions. We discuss possible epigenetic mechanisms that may be related to the action of EGCG.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011–2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Abstract B027: Preclinical efficacy of Tumor Treating Fields (TTFields) applied with PARP inhibitors or carboplatin in ovarian cancer

Abstract Purpose: Ovarian cancer is the leading cause of death among cancers of the female reproductive system. Surgery and platinum-based adjuvant chemotherapy followed by PARP inhibitor (PARPi) maintenance therapy is standard treatment for most patients diagnosed with ovarian cancer. The mechanism of action of PARPi and platinum-based therapy involves the induction of DNA damage, which requires the Fanconi Anemia (FA)- BRCA pathway for repair, making these agents most beneficial in cancers with BRCA mutations. However, 75% of patients with ovarian cancer have BRCA wild type tumors and therefore their benefit from PARPi is limited. TTFields are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cancer cell death. Recent research demonstrated TTFields induce a state of BRCAness in multiple cancer types, as well as anticancer effects in ovarian cancer preclinical models. This study investigated the impact of TTFields concomitant with carboplatin or PARPi in ovarian cancer cell lines. Methods: A2780 (BRCA wild type), OVCAR3 (BRCA mutated), and A2780cis (platinum-resistant) ovarian cancer cells were treated with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or concomitant with application of carboplatin or a PARPi (olaparib or niraparib). Efficacy assessments included cell count, colony formation, and apoptosis induction. The overall effect was calculated by multiplying the effects on cell count and colony formation. Results: TTFields treatment reduced cell count, increased overall effect, and elevated apoptosis. Carboplatin, olaparib, and niraparib exhibited dose-dependent effects in all cell lines. When TTFields were applied together with these drugs, a synergistic interaction was observed in the BRCA wild-type A2780 cells and platinum-resistant A2780cis cells, while an additive effect was noted in the BRCA mutant OVCAR-3 cells. Conclusions: This data implies potential advantages for TTFields concomitant with platinum-based chemotherapy and PARPi in ovarian cancer, even without underlying BRCA mutations. This aligns with the BRCAness state induced by TTFields and suggests a benefit in platinum resistant cancer. Overall, TTFields may augment the efficacy of ovarian cancer treatment in both adjuvant and maintenance settings. Citation Format: Antonia Martinez-Conde, Hila Ene, Kerem Ben-Meir, Roni Frechtel-Gerzi, Eyal Dor-On, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Preclinical efficacy of Tumor Treating Fields (TTFields) applied with PARP inhibitors or carboplatin in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B027.

PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway.

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5-Aza-dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland.

Debate on the oncologic potential of sex steroid preparations

Background. Thanks to numerous worldwide studies, the significant contribution of the hormonal component to the oncological risks of the organs of the female reproductive system is beyond doubt. Of great interest is the analysis of world research on the oncological potential of hormonal drugs, namely COCs and MGT, since this issue continues to be one of the most complex and controversial.&#x0D; Aim. This study aimed to contribution of hormonal factors to the development of cancer of the female reproductive system, namely breast, cervical, endometrial and ovarian cancers.&#x0D; Materials and Methods. The study was conducted on the basis of the Center of Gynecology and Reproductive Technologies of the FSAU “National Medical Research Center “Treatment and Rehabilitation Center” of the Ministry of Health of the Russian Federation, the Department of Oncogynecology of the University Clinical Hospital No. 4 of the I.M. Sechenov First Moscow State Medical University. The analysis of medical documentation for the period from January 2015 to December 2021 was carried out. The study included 1842 patients with verified oncological disease of the female reproductive system, who had a history of taking hormonal drugs of the following pharmacological groups: hormonal contraceptives, menopausal hormone therapy drugs. The age of all patients ranged from 26 to 83 years (mean age 51.98±10.3 years). The control group consisted of 611 patients without oncological diseases, who have a history of indications for taking hormonal drugs of these pharmacological groups.&#x0D; Results. When assessing the effect of the duration of MGT intake on the risk of developing breast cancer, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing breast cancer (HR 1.18; CI 1.02–1.36; p 0.001). Using the Wald method, we found that the probability of developing breast cancer is associated with a BMI of more than 25 kg/m2 and long-term intake of combined MGT for a total of more than 6 years. When assessing the effect of the duration of MGT intake on the risk of developing RTM, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing RTM (HR 1,432; CI 1,172–1,750; p 0.001). Using the Wald method, we found that the probability of developing RTM is associated with the presence of a BMI of more than 25 kg/m2, prolonged MGT intake for a total of more than 6 years and the presence of endometrial hyperplastic processes, adenomyosis, hypertension in the anamnesis. When assessing the effect of the duration of COC intake on the risk of developing breast cancer, it was found that taking COC for a total of more than 7 years was associated with a higher risk of developing breast cancer (HR 1.68; CI 1.1–2.5; p=0.010). According to the Wald method, it was revealed that the probability of developing breast cancer is associated with the presence of HPV type 16, a BMI of more than 25 kg/m2 and prolonged intake of COCs for a total of more than 7 years. When assessing the effect of the duration of MGT intake on the risk of developing PC, it was found that MGT intake for a total of more than 9 years was associated with a higher risk of developing PC (HR 1.65; CI 1.2–2.3; p=0.010). Using the Wald method, we found that the probability of developing RYA is associated with the presence of a BMI of more than 25 kg/m2, MGT intake and the presence of endometrial hyperplastic processes in the anamnesis.&#x0D; Conclusions. With prolonged use of sex steroids, there is a tendency to increase the risk of developing cancer of the female reproductive system. Careful follow-up and limitation of the duration of taking sex steroids in risk groups will reduce carcinogenic risks.

Anticancerous Properties of Tetragonula travancorica (stingless bee) Honey on Reproductive Cancer Cells

Honey from stingless bee is highly regarded as a medicine in many global communities due to its nutritional and therapeutic value. There is a comparatively restricted amount of research on the biological characteristics of stingless bee honey (SBH) in contrast to Indian bee honey (IBH). Therefore, the objective of this research is to explore the anti-cancer properties of Tetragonula travancorica honey. In the present investigation, antioxidant activity of honey was evaluated using ABTS, DPPH and SOD radical scavenging assays. Anti-proliferative effects was examined on various cell lines using the MTT assay. Liquid chromatography-mass spectrometry (LCMS) analysis was employed to characterize the honey. Binding capabilities of compounds identified in SBH on estrogen receptors (ER) α and ER β were explored through Schrödinger Maestro software. Results indicated that SBH effectively scavenged ABTS, DPPH and SOD free radicals with IC50 values of 22, 36.15, and 79.85 v/v, respectively. SBH exhibited anti-proliferative activity against MCF-7 and HeLa cell lines, with IC50 values of 58.11 and 66.68 v/v, respectively. LCMS analysis, shows the presence of methyl syringate, 2-hydroxycinnamic acid, and fumaric acid in SBH which were not present in IBH. Docking experiments determined that these compounds, with the exception of fumaric acid, interacted stronger with the binding sites of ER β than ER α. The comprehensive findings from antioxidant, anti-proliferative, and docking studies underscore the potential anti-cancer properties of Tetragonula travancorica honey, particularly its heightened cytotoxicity against reproductive system cancer cell lines, such as those in the breast and cervix. Keywords : Anti-proliferative, estrogen receptor, stingless bee, cytotoxicity.

Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives.

Reproductive disorders are considered a global health problem influenced by physiological, genetic, environmental, and lifestyle factors. The increased exposure to bisphenols, a chemical used in large quantities for the production of polycarbonate plastics, has raised concerns regarding health risks in humans, particularly their endocrine-disrupting effects on female reproductive health. To provide a basis for future research on environmental interference and reproductive health, we reviewed relevant studies on the exposure patterns and levels of bisphenols in environmental matrices and humans (including susceptible populations such as pregnant women and children). In addition, we focused on in vivo, in vitro, and epidemiological studies evaluating the effects of bisphenols on the female reproductive system (the uterus, ovaries, fallopian tubes, and vagina). The results indicate that bisphenols cause structural and functional damage to the female reproductive system by interfering with hormones; activating receptors; inducing oxidative stress, DNA damage, and carcinogenesis; and triggering epigenetic changes, with the damaging effects being intergenerational. Epidemiological studies support the association between bisphenols and diseases such as cancer of the female reproductive system, reproductive dysfunction, and miscarriage, which may negatively affect the establishment and maintenance of pregnancy. Altogether, this review provides a reference for assessing the adverse effects of bisphenols on female reproductive health.

Risk factors for late detection of cancer in the female reproductive system

BACKGROUND: The pressing issue of the primary diagnosis of oncopathology in later stages of cancer hinders effective implementation of treatment and rehabilitation measures and leads to the disability of the patient. In this aspect, the crucial factor lies in the population’s engagement to medical organizations for examinations according to the road map for the prevention of socially significant diseases.&#x0D; OBJECTIVE: The study aimed to investigate the risk factors for late detection of cancer of the female reproductive system based on the results of a survey on contingents of women with diagnosed cancer of three localizations (cancer of the ovaries, body, and cervix) in the Chechen Republic.&#x0D; MATERIALS AND METHODS: Sample: Female patients diagnosed with cancer of the reproductive system (299 women). Observation units: patients diagnosed with ovarian cancer, uterine body cancer, and cervical cancer. Research base: Republican Oncological Dispensary, Grozny. Research design: face-to-face individual questionnaire survey (2020–2022). Research methods: Initially, survey, statistical, and graphical analysis of the data was conducted. Finally, ranking of risk factors for detection of the disease at late stage and the construction of a decision tree.&#x0D; RESULTS: The key factors with an increase in the risk of late diagnosis of cancer of the female reproductive system to 100.0% were the diagnosis of ovarian cancer, the absence of vaginal discharge outside of menstruation/in menopause, an increase in the size of the abdomen, and late treatment (100.0% absolute risk). In the contingent diagnosed with ovarian cancer, all cases were detected late, while in 22.7% of cases aggregate of patients presented two other nosologies. Among patients who did not notice an increase in the abdomen, late diagnosis of cancer was noted in 26% of patients. Conversely, among those who noted this change, all cases were diagnosed at an advanced stage (p 0.05). Regarding the target indicator “The disease was detected at a late stage” seven risk classes were identified (risk from 7.5% to 100.0%). The high-risk class was characterized by a combination of factors: “Noted pain in the lower abdomen during intercourse (No),” “Blood relatives revealed tumor diseases (No),” and “I noticed an increase in the size of the abdomen (Yes)” (100.0% risk).&#x0D; CONCLUSION: The relevance of the problem of oncogynecology is associated with the need for extensive educational work among the female population with an emphasis on the need for active participation in preventive examinations. Justifying the use of the strategy of “coercion to health” is essential in identifying risk factors and cancerous lesions of the organs of the female reproductive system in the early stages. This will prevent the progression of the malignant tumors and will contribute to effective medical and social prevention of disability.

Identification of a novel cuproptosis-associated lncRNA model that can improve prognosis prediction in uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is a common female reproductive system cancer. Cuproptosis, a new type of mitochondrial respiration-regulated cell death, is associated with several cancer types. Here, we developed a cuproptosis-associated long non-coding RNA (lncRNA) model to predict the prognosis of patients with UCEC and their response to immune-based treatments. RNA sequencing (RNA-seq) and somatic mutation data for UCEC were obtained from The Cancer Genome Atlas (TCGA) database. LncRNAs co-expressed with cuproptosis-related genes were screened. Patients were randomly divided into two groups, one of which was used as training group to build the model, while the other group served as the validation group. A prognostic model comprising 13 cuproptosis-associated lncRNAs was constructed, and each lncRNA was individually related to patient prognosis. Our model clearly distinguished between risk variables in afflicted individuals. The risk score can provide a more accurate prognostic prediction compared with other clinical covariates. Patient groups at various risk groups were different according to tumor mutational burden and tumor immune dysfunction and exclusion analysis. We identified drugs for which patient populations at various risk groups showed higher sensitivity. Our model may contribute to immune related research and clinical decision-making for optimized treatment.

Clinical Presentation and Histological Types of Ovarian Tumor in Patients Admitted in Tertiary Care Center

Background: Ovarian cancer is the eighth most frequent cancer among women worldwide, accounting for 4% of all cancers in the female population. When compared to other reproductive system cancers, ovarian cancer has a high death and morbidity rate. Objectives: The aim of the study was to assess the clinical presentation and histological types of ovarian tumor in patients admitted in tertiary care center. Methods: A descriptive cross-sectional study was conducted to determine the clinical presentation and histopathological types of ovarian tumour diagnosed at Medical college for women, Uttara and Nightingale medical college, Ashulia. The study was approved by the Institutional Review Board (IRB) and 600 patients diagnosed with ovarian tumors were consecutively included in the study from July 2009 to August 2016. The cases were diagnosed and subclassified in accordance with the WHO Classification of Female Genital Tumours, Fourth Edition. Statistical Package for Social Sciences (SPSS) application, version 25, was used for data analysis. Results: Out of Total Gynaecological admission of 4800 patients during the study period, 600 patients were admitted with diagnosis of ovarian Tumor, So occurance was 12.5%. the mean age of the patients was 35 ± 2.09. About 8.6% of the patients had less than 20 years old. 56.6% were within the age group of 21-40, 29.8% were within the age group of 41-60 and only 5% had more than 60 years. The mean Menarche in years was 14.6 ± 1.02 and Menopause in years was 48.7 ± 2.46. Regarding clinical presentation 37.40% had abdominal pain, 55.50% had abdominal mass, 3% had abdominal distension,2% had ascites, 0.50% had menstrual irregularities and 2.50% were asymptomatic. Regarding surgical procedure, 35% undergone Total abdominal hysterectomy and bilateral salpingo-oophorectomy, 18.33% Bilateral salpingo-oophorectomy, 15% Right salpingo-oophorectomy and Left salpingo-oophorectomy recommendation, 13.33% Right cystectomy, 3.33% Left cystectomy. Regarding consistency of tumour 57.33% were cystic, 37% were solid, 5.33% were complex and 0.33% were Diffuse pattern (metastatic tumor). Benign tumors were 77%, borderline 16.67% and malignant 6.33% cases. Out of 462 benign tumors, Serous cystadenoma (230/49.78%), Mucinous cystadenoma (60/12.98%), benign Brenner tumor (10/2.16%), Mature cystic teratoma (110/23.80%), stroma ovarii (10/2.16%), Fibroma (10/2.16%), Fibro-thecoma (12/ 2.59%), leiomyoma (20/4.34%). Out of 38 malignant tumour, Serous cystadenocarcinoma (11/28.94%), mucinous cystadenocarcinoma (6/15.78%), clear cell carcinoma (1/2.63%), Malignant Brenner tumor (1/2.63%), endometroid adenocarcinoma (4/10.52%), squamous cell carcinoma arising in mature teratoma (1/2.63%), Dysgerminoma (7/18.4%), Immature teratoma (1/2.63%), malignant mixed germ cell tumor (1/2.63%), Adult granulosa cell tumor (4/10.52%), Krukenburg tumor (1/2.63%). Survival status was satisfactory; 99.67% patients was alive. Conclusion: The study found that ovarian neoplasms had ambiguous signs and symptoms, were mostly seen in reproductive age groups, and were mostly benign. The proportion of malignant ovarian neoplasms was significantly lower than that of benign ovarian neoplasms. Although incidence of malignant tumor is less common but gynocologists should be more careful in diagnosis of malignancy as ovaries are pelvic organs and definite screening methods are not available and malignancy can occur in any age.

Regression of ovarian cancer xenografts by depleting or inhibiting RLIP

Ovarian cancer (OC) is the most prevalent and deadly cancer of the female reproductive system. Women will continue to be impacted by OC-related morbidity and mortality. Despite the fact that chemotherapy with cisplatin is the main component as the first-line anticancer treatment for OC, chemoresistance and unfavorable side effects are important obstacles to effective treatment. Targets for effective cancer therapy are required for cancer cells but not for non-malignant cells because they are expressed differently in cancer cells compared to normal cells. Targets for cancer therapy should preferably be components that already exist in biochemical and signalling frameworks and that significantly contribute to the development of cancer or regulate the response to therapy. RLIP is an important mercapturic acid pathway transporter that is crucial for survival and therapy resistance in cancers, therefore, we examined the role of RLIP in regulating essential signalling proteins involved in relaying the inputs from upstream survival pathways and mechanisms contributing to chemo-radiotherapy resistance in OC. The findings of our research offer insight into a novel anticancer effect of RLIP depletion/inhibition on OC and might open up new therapeutic avenues for OC therapy.

Design of a novel multi-epitope vaccine candidate against endometrial cancer using immunoinformatics and bioinformatics approaches

Endometrial cancer (EC) is one of the most common cancers of the female reproductive system. Multi-epitope vaccine may be a promising and effective strategy against EC. In this study, we designed a novel multi-epitope vaccine based on the antigenic proteins PRAME and TMPRSS4 using immunoinformatics and bioinformatics approaches. After a rigorous selection process, 14 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes (BCEs) were finally selected for vaccine construction. To enhance the immunogenicity of the vaccine candidate, the pan HLA DR-binding epitope was included in the vaccine design as an adjuvant. The final vaccine construct had 455 amino acids and a molecular weight of 49.8 kDa, and was predicted to cover 95.03% of the total world population. Docking analysis showed that there were 10 hydrogen bonds and 19 hydrogen bonds in the vaccine-HLA-A*02:01 and vaccine-HLA-DRB1*01:01 complexes, respectively, indicating that the vaccine has a good affinity to MHC molecules. This was further supported by molecular dynamics (MD) simulation. Immune simulation showed that the designed vaccine was able to induce higher levels of immune cell activity, with the secretion of numerous cytokines. The codon adaptation index (CAI) value and GC content of the optimised codon sequences of the vaccine were 0.986 and 54.43%, respectively, indicating that the vaccine has the potential to be highly expressed. The in silico analysis suggested that the designed vaccine may provide a novel therapeutic option for the individualised treatment of EC patients in the future. Communicated by Ramaswamy H. Sarma

Metastasis Detection and Clinical Significance According to Localization of Resecting Lymph Nodes in Female Reproductive System Cancers

Metastasis Detection and Clinical Significance According to Localization of Resecting Lymph Nodes in Female Reproductive System Cancers

A case report of long-term successful use of maintenance therapy with PARP inhibitors in the primary treatment of advanced brca-associated ovarian cancer

Background. Ovarian cancer is the third most common cancer of the female reproductive system after cervical and uterine cancer and is diagnosed at stage III–IV in 2 out of 3 cases. Maintenance therapy with PARP inhibitors signifcantly prolongs disease-free and overall survival. The purpose of the study was to demonstrate long-term remission in a patient with advanced ovarian cancer using maintenance therapy with PARP inhibitors (olaparib). Description of the clinical case. A 54-year-old female patient with verifed stage IV ovarian cancer, peritoneal carcinomatosis and left-sided pleurisy received combined modality treatment, including 2 courses of neoadjuvant chemotherapy with paclitaxel/carboplatin, cytoreductive surgery and 6 courses of postoperative chemotherapy with docetaxel/cisplatin. The patient was diagnosed with a somatic BRCA2 gene mutation (c.3708delA), which was detected by tumor DNA sequencing. The patient received maintenance therapy with olaparib for 38 months, resulting in no evidence of disease progression. Conclusion. This clinical case demonstrates the feasibility of using maintenance therapy with PARP inhibitors in a patient with initially disseminated platinum-sensitive ovarian cancer. Olaparib maintenance therapy provides stable long-term remission with no signs of adverse events and determined effect on quality of life of the patient.