Female Reproductive Cancers Research Articles

Exosomal ncRNAs in reproductive cancers.

Extracellular vesicles, particularly exosomes, play a pivotal role in the cellular mechanisms underlying cancer. This review explores the various functions of exosomes in the progression, growth, and metastasis of cancers affecting the male and female reproductive systems. Exosomes are identified as key mediators in intercellular communication, capable of transferring bioactive molecules such as miRNAs, proteins, and other nucleic acids that influence cancer cell behavior and tumor microenvironment interactions. It has been shown that nc-RNAs transported by exosomes play an important role in tumor growth processes. Significant molecules that may serve as biomarkers in the development and progression of male reproductive cancers include miR-125a-5p, miR-21, miR-375, the miR-371 ~ 373 cluster, and miR-145-5p. For female reproductive cancers, significant miRNAs include miR-26a-5p, miR-148b, miR-205, and miRNA-423-3p. This review highlights the potential of these ncRNAs as biomarkers and prognostics in tumor diagnostics. Understanding the diverse roles of exosomes may hold promise for developing new therapeutic strategies and improving treatment outcomes for cancer patients.

Advancing the First Implantable Immune Organs to Treat Ovarian Cancer: Wyss Institute’s iNodes team receives ARPA-H Sprint for Women’s Health Award

Ovarian cancer is more deadly than any other type of female reproductive organ cancer. It is estimated that in 2024, in the U.S. alone, more than 12,000 women will die from the disease because available therapies are not effective. To help overcome this striking deficit in women’s health, ARPA-H has selected a team at the Wyss Institute at Harvard University as an awardee of its Sprint for Women’s Health effort to develop “iNodes” – implantable lymphoid organs containing patients’ immune cells – as an entirely novel form of personalized immunotherapy to treat ovarian cancer.

Identification and validation of miR-21 key genes in cervical cancer through an integrated bioinformatics approach

Cervical cancer is one of the most prevalent female reproductive cancers. miR-21 is a multi-target oncomiR that has shown its potential in regulating several cancers including colon, pancreatic, breast, prostate, ovarian, and cervical cancer. However, the signaling network of miR-21 remains underexplored, and only a limited number of miR-21 gene targets in cervical cancer have been reported. In this context, the present study was undertaken to evaluate the role of miR-21 in cervical cancer by combining in silico analysis with in vitro validation in cervical cancer cells. The miR-21 target genes were predicted using four different prediction tools: miRwalk, DIANA, miRDBs, and TargetScan. A total of 113 overlapping target genes, common in at least three of the prediction tools, were shortlisted and subjected to functional enrichment analysis. The analysis predicted that JAK-STAT, MAPK, neurotrophin, and Ras signaling pathways are significantly (p≤0.05) targeted by miR-21. The MCODE plugin identified the potential cluster in the protein-protein interaction network based on the highest degree of connectivity. After GEPIA2 validation of all 20 hub genes, NTF3, LIFR, and IL-6R were shortlisted for validation in cervical cancer cell lines. The results showed that NTF3, LIFR, and IL-6R were significantly upregulated in the miR-21 knockdown CaSki cell lines in 6.27, 1.92 and 1.71 folds (p≤0.01), respectively. Similarly, in HeLa cell lines expression of NTF3, LIFR, and IL-6R were overexpressed in 4,06, 5.65, 2.42 folds (p≤0.001), respectively. confirming the role of miR-21 in regulating the expression of these genes. Additionally, the knockdown of miR-21 significantly inhibited the secretion of matrix metalloproteinases by CaSki cells. These results highlight that miR-21 could be a potential therapeutic target for cervical cancer, although further preclinical and clinical studies are required to validate its role and efficacy.

ECMTrans-net: Multi-Class Segmentation Network Based on Tumor Tissue in Endometrial Cancer Pathology Images

Endometrial cancer has the second highest incidence of malignant tumors in the female reproductive system, and accurate and efficient endometrial cancer pathology image analysis is one of the important research components of computer-aided diagnosis. However, endometrial cancer pathologic images have the challenges of smaller solid tumors, lesion areas varying in morphology, and difficulty distinguishing solid and non-solid tumors, which would impact the accuracy of subsequent pathological analyses. Therefore, an Endometrial Cancer Multi-class Transformer Network (ECMTrans-net) is proposed to improve the segmentation accuracy of endometrial cancer pathology images. On the one hand, an ECM-Attention is proposed, which can sequentially infer attention maps along three separate dimensions: channel, local spatial, and global spatial, and multiply the attention maps and the input feature map for adaptive feature refinement, solving the problems of the small size of solid tumors and similar characteristics of solid tumors to non-solid tumors and further improving the accuracy of segmentation of solid tumors. On the other hand, an ECM-Transformer is proposed, which can fuse multi-class feature information and dynamically adjust the receptive field, solving the issue of complex tumor features. Experiments on the solid tumor endometrial cancer pathological (ST-ECP) dataset show that the ECMTrans-net performs superior to state-of-the-art image segmentation methods, and the average values of Accuracy, MIoU, Precision, and Dice were 0.952, 0.927, 0.931 and 0.901, respectively.

The Role of Blood Group in Cancer Risk: Correlations with Site, Age, and Body Mass Index

Background: Cancer is a complicated group of diseases in which cells grow and divide without being controlled. It is still one of the main reasons of death in the world, which presents major public health issues. Blood group links to cancer risk have been getting more and more attention over the past few years, among other things being studied. Aim of the study: This study aimed to assess the relation between ABO blood groups and the occurrence of different cancer types among the population of Kirkuk city. Patients and methods: This cross-sectional study was carried out in Kirkuk city from the period 15th October 2023 to 15th May 2024 on cancer patients of Kirkuk's Oncology and Hematology Centre. Data was collected from medical records and patient interviews to examine demographic characteristics, lifestyle factors, medical history, and potential exposures. The study included 398 patients diagnosed with cancer within a specified time frame, selected from medical records of healthcare facilities in the target area.. Blood samples were collected from each participant in the study for determination of blood group and Rh. Results: The study reveals that breast cancer is the most prevalent cancer, accounting for 45.98% of all cases. The study presents the distribution of cancer patients according to their blood groups, with O positive and A positive blood types accounting for the highest percentage at 33.67%. Other blood types such as B positive, AB positive, O negative, B negative, AB negative, and A negative are represented in smaller percentages ranging from 1.26% to 20.60%. The duration of cancer is examined in relation to blood groups, providing insights into mean durations across different ABO blood types and Rh factors. Blood type A exhibits the longest mean duration at 1.71 years, followed closely by blood type B at 1.74 years, while blood type O presents a slightly shorter mean duration at 1.52 years. In the current study, blood group A is predominantly seen in brain cancer for males (100%), with a considerable presence in digestive system cancers, split nearly evenly between males (41.94%) and females (58.06%). Blood group B appears infrequently but is represented in the digestive system and female reproductive cancers, demonstrating a minor presence compared to other groups. Skin cancer shows a potential link between blood group distribution and family history of the disease, suggesting a genetic predisposition or a significant association worth further investigation.

A multimodal cancer rehabilitation programme promoting sense of coherence for women treated for female reproductive cancers: a pilot randomised controlled trial.

To investigate the feasibility, acceptability, and preliminary effects of a theory-driven multimodal cancer rehabilitation intervention (MCRI) programme among Hong Kong Chinese women treated for female reproductive cancers (FRC). A single-blinded randomised controlled trial was conducted in two regional hospitals in Hong Kong involving 35 women treated for FRC. The intervention group (n = 18) received a 12-week MCRI which included 30 modules of app-based health education and three nurse-led individual counselling sessions. The control group (n = 17) received attention from the research nurse through telephone calls. Sense of coherence, health-related quality of life, and cancer-specific distress were measured at baseline (T0), immediately after completion of the intervention (T1) and 12weeks post-intervention (T2). Twelve intervention completers were interviewed to explore the acceptability of the programme. Recruitment, consent, and retention rates, counselling session attendance rate, and app usage were satisfactory. The intervention participants reported to have significant improvement in physical well-being at T1 (Cohen's d effect size (d) = 1.04, 95% CI 0.24, 1.83), sense of coherence (d = 0.76, 95% CI - 0.03, 1.54), and cancer-specific distress (d = 1.03, 95% CI - 1.83, - 0.21) at T2. Interviewed participants acknowledged the benefits of the programme and provided comments for improvement. The MCRI is found to be feasible and acceptable and may improve their sense of coherence, distress, and physical health. A full-scale trial using a larger and more representative sample is warranted to confirm the effects of the programme. Women treated for FRC may be benefited from the MCRI in improving sense of coherence, physical well-being, and distress. This trial was registered on ISRCTN registry with ID ISRCTN73177277.

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.

Predominant localization and ways of metastatic dissemination to the brain of malignant tumors of the female reproductive system

Background. Metastases of the female reproductive system cancer to the brain are rare and reach about 5 % of all cases with metastatic lesions of the central nervous system. The most common metastases are ovarian cancer (0.49–6.1 %), endometrial cancer (0.4–1.2 %) and cervical cancer (0.3–0.9 %). The predominant localization and ways of spreading metastases to the brain in this category of tumors may differ from lung cancer, breast cancer, kidney cancer or melanoma.Aim. To analyze the localization of brain metastases of malignant tumors of the female reproductive system and the ways of dissemination of malignant cells from the primary focus to the central nervous system.Materials and methods. From 2013 to 2020, a total number of 448 patients with metastatic brain tumors from different cancers were operated on at the Department of Neuro‑Oncology of the Federal Center of Neurosurgery (Novosibirsk). Metastases of tumors of the female reproductive system were presented in 32 (7.1 %) cases. The average age was 55.1 (27–72) years. Ovarian cancer was the primary focus in 24 (5.3 %) cases, endometrial cancer – in 6 (1.3 %), cervical cancer – in 2 (0.4 %). Occipital lobe was the most often location for the metastases in the brain and occurred in 10 (31.3 %) patients. Subtentorial localization was on the second place and noted in 9 (28.1 %) cases. Of these, metastases to the cerebellum were registered in 8 cases and in 1 case the metastasis was located in the brain stem.Results. Gross total removal of metastasis was achieved in all 32 patients. Of 9 cases with subtentorial localization of metastasis, only 1 patient had lung metastases verified. Regression of neurological symptoms and improvement of the condition were noted in 16 patients after surgery. The Karnovsky performance score at the time of discharge was 85.2.Conclusion. The subtentorial location of metastases in malignant tumors of the female reproductive system occupies one of the leading places. This is because the dissemination of tumor cells from the pelvis can occur through a Batson vertebral venous system directly to the cerebellum or brain stem without the pulmonary blood circulation and lung dissemination. This should be taken into account for the early diagnosis of subtentorial metastatic brain tumors and referral of these patients for neurosurgical treatment.

Post-diagnostic lifestyle and mortality of cancer survivors: Results from a prospective cohort study

ObjectiveLifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. MethodsThe follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. ResultsDuring a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0–1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). ConclusionsHealthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

The association between pre-existing heart failure and cancer incidence: A systematic review and meta-analysis

Introduction and objectivesCardiovascular diseases (CVD) and cancer are some of the most recognized causes of mortality and morbidity worldwide. Cancer is the second leading cause of death in heart failure (HF) populations. Recent studies have hypothesized that HF might promote the development and progression of cancer. We aim to analyze and discuss the most recent evidence on the relationship between HF and cancer development. MethodsFrom inception to November 2022, we searched PubMed, Web of Science and ClinicalTrials.gov for relevant articles on patients with HF and a subsequent cancer diagnosis that reported outcomes of overall and site-specific cancer incidence, or mortality. ResultsOf 2401 articles identified in our original search, 13 articles met our criteria. Studies reporting risk rate estimates were summarized qualitatively. Studies reporting hazard ratios (HRs), or relative risks were combined in a meta-analysis and revealed that HF was associated with an increased overall cancer incidence with a HR=1.30 (95% CI: 1.04–1.62) compared with individuals without HF. Subgroup analyses by cancer type revealed increased risk for lung cancer (HR=1.87; 95% CI: 1.28–2.73), gastrointestinal cancer (HR=1.22; 95% CI: 1.03–1.45), hematologic cancer (HR=1.60; 95% CI: 1.23–2.08) and female reproductive cancer (HR=1.67; 95% CI: 1.27–2.21). Mortality from cancer was higher in HF patients compared with non-HF subjects with a HR=2.17 (95% CI: 1.23–3.84). ConclusionsOur systematic review and meta-analysis revealed that HF may result in a subsequent increase in cancer incidence as well as in cancer-related mortality. The most common cancer subtypes in HF patients were lung, female reproductive system, and hematologic cancers. Further research is needed to understand this association better and to provide the best cardiological and oncological care.

Role of body mass index and weight change in the risk of cancer: A systematic review and meta-analysis of 66 cohort studies.

This study was designed to evaluate the effects of body mass index (BMI) and weight change on the risk of developing cancer overall and cancer at different sites. We searched PubMed and other databases up to July 2023 using the keywords related to 'risk', 'cancer', 'weight', 'overweight', and 'obesity'. We identified eligible studies, and the inclusion criteria encompassed cohort studies in English that focused on cancer diagnosis and included BMI or weight change as an exposure factor. Multiple authors performed data extraction and quality assessment, and statistical analyses were carried out using RevMan and R software. We used random- or fixed-effects models to calculate the pooled relative risk (RR) or hazard ratio along with 95% confidence intervals (CIs). We used the Newcastle-Ottawa Scale to assess study quality. Analysis included 66 cohort studies. Compared to underweight or normal weight, overweight or obesity was associated with an increased risk of endometrial cancer, kidney cancer, and liver cancer but a decreased risk of prostate cancer and lung cancer. Being underweight was associated with an increased risk of gastric cancer and lung cancer but not that of postmenopausal breast cancer or female reproductive cancer. In addition, weight loss of more than five kg was protective against overall cancer risk. Overweight and obesity increase the risk of most cancers, and weight loss of >5 kg reduces overall cancer risk. These findings provide insights for cancer prevention and help to elucidate the mechanisms underlying cancer development. Reviewregistry1786.

A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge regarding Warning Signs and Prevention of Reproductive Cancer among Female Non Health Professionals in a selected Hospital, Mangaluru

Female reproductive cancer is cancer of the organs related to female reproductive system. In order to identify these cancers in early stage women needs to have knowledge regarding warning signs of these cancers. Possessing knowledge helps to reduce mortality and enhances number of cure rate among women’s at risk of reproductive cancer and it is one of the prime responsibility of all health care personnel’s to disseminate information regarding warning signs and prevention of reproductive cancer. The present investigation was aimed to evaluate the effectiveness of structured teaching programme on knowledge regarding warning signs and prevention of reproductive cancer among female non health professionals working in selected hospital and to find out the association between the pre test knowledge score regarding warning signs and prevention of reproductive cancer and their selected demographic variables. The research design used in the study was pre – experimental one group pre-test post-test and non-probability purposive sampling technique was used to draw sample. The data was collected from 60 non health professionals using the structured knowledge questionnaire. Structured teaching programme was conducted and post-test was administered after 7 days using the same structured knowledge questionnaire to find out the effectiveness of structured teaching programme. The results revealed that the overall mean percentage knowledge score in the pre-test and post-test were 34% and 74.56% respectively. Enhancement mean percentage knowledge score was found to be 40.56%. The statistical paired ‘t’ test (t= 44.44) indicates that enhancement in the mean percentage knowledge score was found to be significant at 0.05 level for all the aspects under study. The association found to be significant between pre-test knowledge scores &amp; selected socio demographic variables such as age, educational status, occupation, monthly income, and information regarding reproductive cancer at 0.05 levels (P&lt; 0.05). There is no significant association and some demographical variable such as religion, marital status and family history of cancer, presence of children.

Incidence and mortality of endometrial cancer in China, data from China Cancer Registry Annual Report, 2004-2017

Objective: To analysis the incidence rate and mortality rate of endometrial cancer in China from 2004 to 2017 according to the data from China Cancer Registry Annual Report. Methods: The incidence and mortality data of endometrial cancer were extracted from the China Cancer Registry Annual Report 2004 to 2017, and the incidence, mortality, number of new cases, number of deaths were extracted according to the region (national, urban, rural and eastern, middle and western areas) and the age composition of population to estimate the incidence and mortality of endometrial cancer nationwide. The age-standardized incidence rate and mortality rate were calculated based on the Chinese standard population in 2000 (ASIRC, ASIRW) and Segi's world population (ASMRC, ASMRW). Join Point regression was used to calculate the annual percentage change of morbidity rate, and Cochran-Armitage trend test was used to analyze the changing trend of morbidity and mortality. Results: From 2004 to 2017, the number of women covered by the China Cancer Registry Annual Report has increased from 35 571 657 to 215 201 995, and the total population of the covered areas has increased from 5.53% to 31.39%. The crude incidence rate of endometrial cancer increased from 6.20/100 000 to 10.06/100 000, and showed an upward trend over time (P<0.001). After adjusting for age, ASIRC increased from 5.75/100 000 in 2004 to 6.79/100 000 in 2017, and ASIRW increased from 5.60/100 000 in 2004 to 6.56/100 000 in 2017, both showing an upward trend over time (all P<0.001). The crude incidence rates in urban area and rural area were respectively 10.89/100 000 and 9.25/100 000 in 2017, and the ASIRC was higher in urban than rural areas (7.14/100 000 vs 6.43/100 000) after adjusting for age. The ASIRW was higher in eastern areas than middle areas and western areas (7.16/100 000 vs 6.44/100 000 vs 5.60/100 000). The incidence rate in rural areas showed more significant growth than urban areas [annual percent change (APC): 3.2% vs 0.7%, P<0.001]. The age-specific incidence rate increased with age and reached a peak in the age group of 50-54 years (25.70/100 000). Incidence rate in the under-40 age group increased more in rural areas than in urban areas (69.84% vs-7.09%). From 2004 to 2017, the age-standardized mortality rate shows a decreasing trend, with the ASMRC from 1.83/100 000 to 1.47/100 000, and the ASMRW from 1.81/100, 000 to 1.46/100, 000. There was no significant difference between urban and rural areas in mortality of endometrial cancer. Age-specific mortality rates increased with age, reaching a peak in the age group 85 years and older (13.16/100 000). Conclusions: Recent years, there was an increasing incidence rate of endometrial cancer in China. Especially in rural areas, the incidence rate of endometrial cancer is increasing rapidly in young women under 40 years of age. There were differences between urban and rural areas and regions in the incidence rate of endometrial cancer. The incidence rates of endometrial cancer in some high-income cities have occupied the first place of female reproductive system malignant cancers. The age-standardized mortality rate of endometrial cancer shows a decreasing trend.

Potential tools for predicting response to chemotherapy in OC: Assessment of immune dysbiosis, participant’s self-rated health and microbial dynamics

Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.

Abstract B002: Exploiting JAK/STAT signaling to inhibit highly advanced and resistant forms of ovarian cancer

Abstract Ovarian cancer is the most fatal of all female reproductive cancers due to its late detection, aggressive nature, and propensity to develop resistance to current standards of care. Despite initial responses to first line platinum- and paclitaxel-based chemotherapies, &amp;gt;70% of ovarian cancers recur with increasingly resistant disease. Targeted therapies, including PARP-inhibitors (PARPi) and VEGF-inhibitors, are being included in the front-line setting; and while they have improved progression-free survival in a subset of patients, they have thus far failed to improve overall survival in patients without specific genetic signatures. With the broad uptake of PARPi, PARPi-resistance is becoming common. Once resistance develops, nearly all patients die of their disease and there is an obvious need to elucidate the basis for chemotherapy- and PARPi-resistance and devise novel approaches to overcome resistance. Using a small molecule drug screen, we identified lestaurtinib, a known tyrosine kinase inhibitor as a potent inhibitor of treatment naive and highly advanced models of ovarian cancer. Lestaurtinib was originally developed to target FLT3, a protein not expressed in any ovarian cancer models we’ve tested. To identify lestaurtinib targets, we preformed phospho-proteomics in parallel with RNAseq and discovered the JAK/STAT signally pathway as a top hit. We confirmed that essential components of JAK/STAT signaling are constitutively activated in chemotherapy- and PARPi-resistant cells, suggesting that induction of this pathway may drive resistance. Importantly, we found that lestaurtinib-sensitive patient-derived-xenografts (PDXs) exhibited higher expression of multiple JAK/STAT signaling pathway members compared to PDXs that did not respond to lestaurtinib. Genetic knockdown of STAT1 and STAT3 via siRNA, or knockout via CRISPR/Cas9, resulted in significant growth inhibition of sensitive and resistant models, confirming their importance in maintaining cell viability and progression. Combining lestuartinib with standard-of-care cisplatin or olaparib, a PARPi, was shown to be synergistic in multiple models, indicating that pharmacological inhibition of JAK/STAT signaling has the potential to alleviate drug resistance. Finally, we assessed a panel of JAK/STAT inhibitors that interfere at various levels of the pathway and found profound differences in their ability to block STAT-phosphorylation and inhibit cell proliferation. Thus, it is critical to further define the mechanisms by which these drugs function to selectively suppress JAK/STAT signaling in order to elucidate specific nodes of the pathway that drive ovarian cancer progression. Ongoing studies are aimed at identifying the unique roles of STAT1 and STAT3, the specific contributions of their tyrosine and serine phosphorylation, and the relevance of up-/down-stream mediators of the JAK/STAT pathway on ovarian cancer cell growth with the goal of informing future clinical trials. Citation Format: Esther Rodman, Michael Emch, Archit Bajaj, Xiaojia Tang, Xiaonan Hou, Scott Kaufmann, Krishna Kalari, John Weroha, John Hawse. Exploiting JAK/STAT signaling to inhibit highly advanced and resistant forms of 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 B002.

MiRNAs: Emerging Agents for Therapeutic Effects of Polyphenols on Ovarian Cancer.

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.

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.

Improvement of Knowledge in Reproductive Organ Cancer Prevention and Anticancer Herbal Compounding in Ambarketawang

Cervical cancer and breast cancer are cancers of the female reproductive organs. The aim of the study was to improve the knowledge of participants in preventing exposure to female reproductive cancer and herbs high in antioxidants as well as enhancing the skills of combining or choosing anti-cancer herbs. The method used is lectures and discussions. Analysis using pre-post-test and correlation tests. The result of this study is there’s a 17.38% increase in decay and ability to select anti-cancer herbal ingredients. However, differences in education and age do not indicate any relationship. In conclusion, lectures and discussions on cancer, herbs and combination training of herbs can enhance the knowledge and skills of participants. Age and level of education have no influence on efforts to improve knowledge. The future research needs to test the daily beverages to the participants and their family.

Reproductive health issues of concern among Nigerians: an online survey

Background: Reproductive health is often neglected due to various reasons including poor access to information and services. This study was undertaken to get an understanding of what reproductive health issues are of concern to Nigerians and their suggestions for improvement of services in order to meet their needs. Methods: The study was an anonymous online survey carried out using Google Forms. Statistical analyses including rates and comparative analyses were carried out using MINITAB statistical software version 19. Results: The most common reproductive health issues of concern to respondents were sexual health (29.59%), contraception (23.47%), infections (21.43%), fertility issues (17.35%, and female reproductive tract cancer (13.27%). Other concerns were limited access to reproductive health information and services including awareness and education of men and young people (5.10%), availability and affordability (2.04%), getting the right information (1.02%), and ability to discuss reproductive health issues (1.02%). The most common suggestions for improvement included having more information (65.00%), greater involvement of men (62.00%), improved access to services (56.00%), and greater involvement of young people (39.00%). The preferred media of information included social media (20.00%), email (20.00%), and health workers including door-to-door services and seminars in schools (13.85%). Other preferred media of information included radio (4.62%), print media (3.08%), parents/family (1.54%), and SMS messages (1.54%). Conclusions: For meaningful impact, reproductive health interventions should ensure availability of information and services that are inclusive of adolescents and young people, men and older persons, through various channels such as school seminars, health workers, traditional and social media, and other technologies.

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.