PARP inhibitor (PARPi)-based synthetic lethal therapies have displayed limited benefits in BRCA-proficient ovarian cancer. To potentiate the application of PARPi, an ultrasound contrast agent OLA-NDs for delivery of the PARPi olaparib (OLA) was established for enhancing DNA damage by blocking DNA repair. OLA-NDs were endowed with endogenous pH- and exogenous ultrasound (US)-responsiveness to target tumors, as well as contrast-enhanced US imaging for diagnostic and therapeutic integration. OLA-NDs could upregulate NOX4 to induce oxidative stress and sensitize BRCA wild-type A2780 cells to DNA oxidative damage through the utilization of ultrasound-targeted microbubble destruction (UTMD). In addition, the strategy further increased ROS production by interfering with mitochondrial function, thereby exacerbating DNA double-strand breaks (DSBs) and inducing mitochondria-mediated apoptosis. As a consequence, the combined application of UTMD and OLA-NDs demonstrated significant antitumor effects in vitro and in vivo. This combined strategy of amplifying oxidative damage improved lethality by promoting DNA DSBs and apoptosis with reduced adverse side effects, which would provide new insight for the clinical application of PARPi in BRCA-proficient ovarian cancer.

Symptoms occur in up to 75% of patients with early-stage ovarian cancer; as such, using a symptom inventory (SI) to stratify which patients should receive screening for ovarian cancer is an attractive approach to mitigate false-positives. We report on the feasibility and results of a prospective four-question SI that assessed the following symptoms: abdominal pain, bloating, early satiety, and urinary complaints. Frequency and duration of symptoms were not assessed.

A SI was added to the standard pre-appointment check-in process via the electronic medical record's (EMR) patient portal for all annual or new patient visits in a generalist obstetrics and gynecology faculty practice in patients over 40 years of age. IRB exemption was granted. Data were extracted from the EMR, compiled in REDCap, and analyzed in R.

A total of 589 individual patients were included in the final analysis. The median age of the participants was 50 years (range: 40-86). 27.8 % of patients experienced at least one symptom in the prior year, and the most commonly reported symptom was urinary urgency/frequency (14.9 %). Patients with a history of medical comorbidities such as depression, uterine fibroids, endometriosis, and irritable bowel syndrome were more likely to screen positive on the SI. No cancers have been diagnosed to date.

Implementing a SI using the EMR is feasible but is influenced by the presence of pre-existing diagnoses. The effectiveness of an EMR-based SI pre-screen as a selection criterion for early detection requires further study and assessment of frequency and duration of symptoms should be considered.

To explore the feasibility of Dual-Energy Computed Tomography (DECT) in distinguishing metastatic from non-metastatic lymph nodes (LNs) in ovarian High-Grade Serous Carcinoma (HGSC), and to assess the incremental diagnostic value of combining DECT with morphologic parameters in differentiating metastatic and non-metastatic LNs.

From October 2021 to May 2024, 141 LNs from 39 patients with HGSC who underwent DECT were retrospectively enrolled. LNs were matched with the pathological report. Five morphologic parameters and nine DECT parameters were assessed. DECT parameters were obtained from both the arterial and venous phases, including the attenuation at 40 and 70 keV, slope of the spectral Hounsfield unit curve (λHu), Virtual Non-Contrast (VNC), Iodine Concentration (IC), Normalized Iodine Concentration (NIC), electron density (Rho), effective atomic number (Zeff) and Dual-Energy Index (DEI). Independent-sample Student's t test was used to compare continuous variables, while multivariable binary logistic regression analyses was applied to identify independent predictors for LN metastasis in the morphology, DECT, and combined models. Receiver Operating Characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these three models in differentiating metastatic from non-metastatic LNs.

86 metastatic LNs and 55 non-metastatic LNs were finally enrolled in our study. The short diameter (S), long diameter (L), and S/L ratio were significantly larger in metastatic LNs compared to non-metastatic LNs (9.69 ± 4.06 vs. 6.37 ± 1.24 mm, P < 0.001; 13.99 ± 5.36 vs.9.61 ± 2.30 mm, P < 0.001; 0.70 ± 0.15 vs. 0.67 ± 0.12, P = 0.023). In the venous phase, λHU, VNC and Rho were significantly higher in metastatic LNs compared to non-metastatic LNs (-3.596 ± 1.115 vs. -4.234 ± 1.077, P = 0.001; 24.242 ± 9.867 vs. 15.826 ± 11.830, P < 0.001; 32.557 ± 8.023 vs. 26.936 ± 9.420, P < 0.001), while IC, NIC, Zeff, DEI were significant lower in metastatic LNs than non-metastatic LNs (1.872 ± 0.678 vs. 2.404 ± 1.140, P = 0.001; 38.309 ± 14.443 vs. 47.247 ± 22.270, P = 0.005; 8.513 ± 0.320 vs. 8.719 ± 0.360, P = 0.001; 0.014 ± 0.006 vs. 0.018 ± 0.007, P = 0.045). The Area Under the Curve (AUC) of morphology model and DECT model were 0.793 (95 %CI: 0.721-0.862) and 0.762(95 %CI: 0.690-0.825), respectively. The combination of the morphology model and DECT model revealed optimal diagnostic performance (AUC = 0.845; 95 %CI: 0.780-0.896), which was significantly higher than that of the individual models (P = 0.015, P = 0.006, respectively).

DECT parameters provide incremental diagnostic value in assessing metastatic LNs in patients with HGSC. The combination of the morphology and DECT models significantly improves diagnostic performance compared to the standalone morphology model.

While excess body fatness in older adulthood has been linked to ovarian cancer, the influence of changes in body fatness over time is unclear. This study examined the association between adulthood trajectories of body mass index (BMI), a proxy for body fatness, and ovarian cancer.

In a population-based case-control study (440 cases, 820 controls), we used a group-based trajectory approach to identify BMI trajectories from age 20-70. Using unconditional logistic regression, we estimated adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) for the associations between the estimated trajectories and ovarian cancer.

We identified three distinct BMI trajectories: a normal-stable trajectory, a normal-to-overweight trajectory and an overweight-to-obese trajectory, which included 63.2 %, 31.0 % and 6.8 % of the population, respectively. Multivariable aORs suggested that participants with normal weight at the onset of adulthood who became overweight over their adulthood time did not differ in their risk of ovarian cancer compared to those who maintained a normal weight throughout adulthood (aOR (95 %CI): 0.89 (0.69-1.16)). Among those in the overweight-to-obese trajectory, the aOR (95 %CI) was 1.45 (0.87-2.43), and thus in the direction of an increased ovarian cancer risk compared to those who maintained a normal weight.

Our findings underscore the need for further research to clarify the role of body fatness across the lifetime in the etiology of ovarian cancer.

Circular RNAs (circRNAs) have emerged as promising biomarkers and therapeutic targets in gynecological cancer. The present review explored developments in circRNA research in ovarian, endometrial and cervical cancer. circRNA biogenesis, functions and roles in cancer pathogenesis have been discussed, focusing on their potential as diagnostic and prognostic markers. Furthermore, circRNAs mechanisms of action, including miRNA sponging, protein scaffolding and peptide encoding were examined, highlighting specific circRNAs implicated in each cancer type and their clinical significance. The unique properties of circRNAs, such as stability and tissue-specific expression, make them ideal candidates for biomarker development. By synthesizing the currently available literature and identifying future research directions, the present review underscored circRNAs potential to improve gynecological cancer management through novel diagnostic tools, prognostic markers and targeted therapies.

Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.

S. Plasma lipids in circulation are integral to the physiopathological processes of the ovary and may impact the development of various ovarian conditions, including ovarian cancer (OC). This study utilized a two-sample Mendelian randomization method to examine the causal link between changes in 179 plasma lipid groups and ovarian cancer (OC) to gain deeper insights into this association. We used the inverse variance weighted (IVW) method as the main tool for analysis. We utilized statistical data from plasma lipidomics involving 7,174 Finnish individuals and OC data from the FinnGen consortium, including 2,339 European OC patients and 222,078 European healthy controls. Our analysis revealed that elevated levels of four plasma lipids-Phosphatidylcholine (14:0_16:0, O-18:2_18:2, 16:0_20:4)-are linked to an increased risk of OC, while Sphingomyelin (d34:2) seems to act as a protective factor(all P < 0.05). We also conducted tests for heterogeneity and pleiotropy in the MR results. Additionally, reverse MR analysis indicated that OC does not affect plasma levels of these lipids. To determine whether the observed significant plasma lipids influence OC through common risk factors, we selected BMI as a confounder for multivariable Mendelian randomization (MVMR) analysis. The results showed that Sphingomyelin (d34:2) levels remained significantly associated with OC even after including BMI as an exposure factor. Furthermore, we investigated whether these four lipids mediated the effect of BMI on OC but found no evidence supporting their mediating role. In summary, our findings confirm a causal link between certain plasma lipid species and OC, providing fresh perspectives for risk evaluation and potential therapeutic strategies.

High-grade serous ovarian cancer (HGSOC) remains an urgent unmet clinical need, with more than 70% of patients presenting with metastatic disease. Many patients develop large volumes of ascites, which promotes metastasis and is associated with poor therapeutic response and survival. Immunotherapy trials have shown limited success, highlighting the need to better understand HGSOC immunology. Here, we analyzed cytotoxic lymphocytes [natural killer (NK), T, and innate T cells] from patients with HGSOC and observed widespread dysfunction across primary and metastatic sites. Although nutrient rich, ascites was immunosuppressive for all lymphocyte subsets. NK cell dysfunction was driven by uptake of polar lipids, with associated dysregulation in lipid storage. Phosphatidylcholine was a key immunosuppressive metabolite, disrupting NK cell membrane order and cytotoxicity. Blocking lipid uptake through SR-B1 protected NK cell antitumor functions in ascites. These findings offer insights into immune suppression in HGSOC and have important implications for the design of future immunotherapies.

Triphenyl phosphonium conjugated amphiphilic peptides are self-assembled into micelles that show potential antimicrobial activity against drug resistant strains. Moreover, these peptides destroy ovarian cancer cells through mitochondrial reactive oxygen species (ROS) generation while maintaining cytocompatibility with HEK 293 (non-cancerous) cells, indicating the emergence of biomaterials with anticancer and antimicrobial activities.

Ovarian cancer stem cells (OCSCs) play a pivotal role in the initiation, maintenance, and progression of ovarian cancer, functioning through complex molecular mechanisms that are closely linked to metastasis and drug resistance. The complexity of these underlying mechanisms contributes to cancer hallmarks such as the high plasticity of OCSCs, leading to chemotherapy resistance; activation of invasion and metastasis, epigenetic reprogramming, and cell death resistance; and deregulation of cellular metabolism. OCSCs are characterized by the expression of markers including ALDH, CD133, CD44, and CD24. They preserve their stemness through intricate molecular mechanisms that involve interactions with the tumor microenvironment and various signaling pathways. To investigate these molecular mechanisms, both in vitro and in vivo models of OCSC have been established. The results of these studies can be applied in clinical practice, facilitating the development of various new therapies. This review aims to provide a deeper understanding of the mechanisms through which OCSCs function, highlighting significant opportunities for future research aimed at improving ovarian cancer treatment.

Metabolic reprogramming is a hallmark of cancer and de novo lipogenesis (DNL) accelerates the progression of ovarian cancer. In this study, we investigated the effects of cardamonin, a natural compound potential to suppress various malignancies, on the lipid anabolism in ovarian cancer. Cell proliferation was assessed using CCK-8 and clone formation assay. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining and mitochondrial membrane potential (MMP) was measured with JC-10 probe. Free fatty acids (FFA) was measured by fluorescence using acyl-CoA oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity was analyzed by spectrophotometric assay using palmitoyl-CoA and DTNB (5,5'-dithio-bis-(2-nitrobenzoic acid)) reaction. mRNA expression was measured by Quantitative Real-Time PCR. Protein expression was analyzed through western blotting and immunofluorescence. Raptor was knocked down by shRNA and Raptor was overexpressed by lentiviral transfection. The antitumor effect of cardamonin was evaluated using a xenotransplantation tumor bearing mouse model. Cardamonin suppressed the cell proliferation, induced cell apoptosis and triggered mitochondrial damage in ovarian cancer cells. Cardamonin inhibited the protein expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes and decreased FFA content and CPT-1 activity. Additionally, cardamonin inhibited the activation of mechanistic target of rapamycin complex 1 (mTORC1) and expression of regulatory-associated protein of mTOR (Raptor). Raptor knockdown abolished the inhibitory effect of cardamonin on mTORC1 and SREBP1. Furthermore, cardamonin inhibited mTORC1 activation and lipogenic proteins expression induced by Raptor overexpression. Cardamonin reduced the tumor growth and fatty acid synthase of the tumors, as evidenced by decreased expression of Ki-67 and FASN. It suggests that cardamonin suppresses mTORC1/SREBP1 through reducing the protein level of Raptor and inhibits DNL of ovarian cancer.

To determine differentiating CT imaging features of primary ovarian cancers from ovarian metastases of gastrointestinal origin.

Retrospective study of 50 patients with new ovarian lesions on CT, half were primary ovarian cancers and half gastrointestinal metastases. Two blinded independent readers described tumor characteristics on CT (size, laterality, margin, etc.) and ancillary features (ascites, peritoneal seeding, lymphadenopathy, etc.). Patient age, sex, cancer history, and tumor marker levels for CA-125 and CEA were collected. Wilcoxon test and Pearson's chi-squared test were used for statistical analysis.

50 patients with mean age of 62.1 years were included. Ovarian metastases were more likely to be cystic/mainly cystic (p=0.013), have smooth margins (p=0.011), and have no/mild enhancement (p<0.001). Primary ovarian lesions were associated with moderate to large volume of ascites (p=0.047) and more commonly seen with lymphadenopathy (p=0.008). Laterality was not significantly different between the two groups. CA-125 level was more commonly elevated in primary ovarian lesions (87% vs 50%, p=0.018), and with much higher values (1076.5 vs 155.1, p=0.013). CEA level was more commonly elevated in metastatic ovarian lesions (83.3% vs 15.4%, p<0.001), and with higher values (72.4 vs 2.1, p<0.001).

Ovarian metastases were more frequently smooth-margined and cystic with little enhancement. Primary ovarian lesions were more commonly associated with lymphadenopathy and larger volume of ascites. Tumor markers CEA and CA-125 were more frequently elevated in metastatic and primary lesions, respectively. Cancer history was the only variable that increased the odds of metastasis and therefore it is important to always correlate with history of cancer.

Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment.

Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote metastasis in patients with ovarian cancer (OC). Here, we try to further understand the mechanism by which CAFs-derived exosomes (CAFs-Exo) promoted angiogenesis in OC. We intersected differentially expressed genes in OC cells after CAFs-Exo treatment in the GSE147610 dataset with a list of transcription factors to identify homeobox protein hox-D11 (HOXD11) as a possible cargo of CAFs-Exo. HOXD11 encapsulated by CAFs-Exo enhanced colony formation, migration, and invasion of OC cells. HOXD11 bound to the promoter of fibronectin (FN1) and promoted its transcription. HOXD11 knockdown from CAFs-Exo significantly repressed the VEGF and CD31 protein expression and tube formation, viability, and migration of human umbilical vein endothelial cells (HUVEC) and slowed angiogenesis and tumor growth in mice. Furthermore, we found that overexpression of FN1 increased the expression of angiogenic factors and activity of HUVEC in the presence of HOXD11 knockdown. These results verify the significant contribution of CAFs-Exo to angiogenesis in OC, which could be partially due to the promotion of FN1 mediated by HOXD11.

Ovarian cancer (OC), owing to its substantial heterogeneity and high invasiveness, has historically been devoid of precise, individualized treatment options. This study aimed to establish integrated consensus subtypes of OC using different multiomics integration methodologies.

We integrated five distinct multiomics datasets from multicentric cohorts to identify high-resolution molecular subgroups using a combination of 10 and 101 clustering and machine learning algorithms, respectively, to develop a robust consensus multiomics-related machine learning signature (CMMS).

Two cancer subtypes with prognostic significance were identified using multiomics clustering analysis. 10 essential genes were identified in the CMMS. Patients in the high CMMS group exhibited a poorer prognosis, with a "cold tumor" phenotype and an immunosuppressive state with reduced immune cell infiltration. In contrast, patients in the low CMMS group exhibited a more favorable prognosis, with immune activation and a "hot tumor" phenotype characterized by increased tumor mutation burden, tumor neoantigen burden, PD-L1 expression, and enriched M1 macrophages. Eight independent immunotherapy datasets were validated to further corroborate our findings regarding patients in the low CMMS group who responded better to immunotherapy.

CMMS detection has significant utility in the prognosis of patients at an early stage and identification of potential candidates for immunotherapy.

This study identifies barriers and facilitators for implementing opportunistic salpingectomy (OS) during non-gynecological abdominal surgeries from a healthcare provider perspective.

From October 2023 to July 2024, a mixed-method study was conducted. The qualitative phase involved semi-structured focus group interviews and individual interviews with specialists in surgery (gynecologists, general surgeons, urologists, and residents) and policymakers to identify barriers and facilitators for implementing OS during non-gynecological surgery. The quantitative phase consisted of a cross-sectional web-based survey assessing the importance of these barriers and facilitators. The study utilized the standardized implementation frameworks to categorize the factors into six domains: innovation, patient, healthcare professional, social setting, organization, and economic and financial context.

In the qualitative phase, 38 healthcare professionals and policymakers identified 38 barriers and 28 facilitators. Barriers were found in all domains and mainly included increased workload, unclear invoicing, and variations in eligible surgeries. Facilitators included the poor prognosis of ovarian cancer, simplicity of OS, and availability of counseling materials. The quantitative survey revealed that 75% of gynecologists, 60% of surgeons, and 61% of urologists supported offering OS during non-gynecological abdominal surgeries. Barriers identified included the ambiguity regarding which patients are eligible for OS, the perceived complication risks of OS, the increased workload as a result of adding OS, and the unclarity around invoicing an OS. Facilitators included the poor prognosis of ovarian cancer, the availability of uniform counseling materials, education on counseling and technical performance of OS, involvement of a gynecologist during the counseling, and clear agreements between the departments within hospitals.

Key barriers to OS implementation in non-gynecological surgeries include unclear invoicing and increased workload, while significant facilitators are the availability of counseling materials and education on counseling and technical performance of OS. Addressing these barriers and leveraging facilitators could enhance OS adoption, potentially reducing ovarian cancer incidence.

Cancer development is driven by genetic alterations, particularly cancer driver mutations (CDMs), which are associated with aggressive phenotypes and shorter survival. In contrast, higher mutation loads caused by microsatellite instability (MSI) or mismatch repair deficiency (MMRd) can induce anti-cancer immunity, leading to tumor shrinkage and improved responses to immune checkpoint inhibitor (ICI) therapies. However, understanding how CDMs and MSI/MMRd influence cancer evolution remains limited. We opted uterine corpus endometrial carcinoma (UCEC) as a model in this study due to its MSI-high/MMRd characteristics. Somatic mutation screening revealed that UCEC has a significantly higher mutation rate in cancer driver genes compared to ovarian cancer (OVCA) and cervical squamous cell carcinoma (CSCC), despite these cancers arising from histologically connected organs in the reproductive tract. Interestingly, these CDMs did not necessarily drive tumor progression. Using a cutoff of 7.0 (mutations/Mb) for tumor mutation burden (TMB), we classified UCEC patients into two groups with distinct clinical features, genetic profiles, and drug sensitivities. Among the known CDMs, TP53 mutations and their functional networks emerged as key drivers in UCEC progression, while mutations in CTNNB1, PTEN, and ARID1A may enhance anti-tumor immunity, correlating with longer overall survivals. Drug screening using GDSC and CTRPv2 databases suggested that GSK-3 inhibitor IX may be effective for treating aggressive UCEC patients with a non-MSI phenotype. Curcumin showed efficacy for UCEC patients with MSI, especially with ICI therapy. Our study highlights the importance of immune regulation and tolerance over CDMs in cancer development, particularly in those with an MSI-high/MMRd phenotype. We propose that TMB could serve as a valuable screening method alongside molecular and histopathological classifications to guide treatment strategies for UCEC patients.

Conventional ascitic fluid cytology for detecting ovarian cancer is limited by its low sensitivity. To address this issue, this multicenter study developed patch image (PI)-based fully supervised convolutional neural network (CNN) models and clustering-constrained attention multiple-instance learning (CLAM) algorithms for detecting ovarian cancer using ascitic fluid cytology. Whole-slide images (WSIs), 356 benign and 147 cancer, were collected, from which 14,699 benign and 8025 cancer PIs were extracted. Additionally, 131 WSIs (44 benign and 87 cancer) were used for external validation. Six CNN algorithms were developed for cancer detection using PIs. Subsequently, two CLAM algorithms, single branch (CLAM-SB) and multiple branch (CLAM-MB), were developed. ResNet50 demonstrated the best performance, achieving an accuracy of 0.973. The performance when interpreting internal WSIs was an area under the curve (AUC) of 0.982. CLAM-SB outperformed CLAM-MB with an AUC of 0.944 in internal WSIs. Notably, in the external test, CLAM-SB exhibited superior performance with an AUC of 0.866 compared with ResNet50's AUC of 0.804. Analysis of the heatmap revealed that cases frequently misinterpreted by AI were easily interpreted by humans, and vice versa. Because AI and humans were found to function complementarily, implementing computer-aided diagnosis is expected to significantly enhance diagnostic accuracy and reproducibility. Furthermore, the WSI-based learning in CLAM, eliminating the need for patch-by-patch annotation, offers an advantage over the CNN model.

Most ovarian cancer patients present with advanced disease and there are few targeted therapies; consequently, five-year survival for ovarian cancer remains below 50%. We described the anticipatory unfolded protein response (a-UPR) hyperactivator, ErSO, which induced profound and often complete regression of breast cancer in mouse models. Here we explore the effectiveness of ErSO against ovarian cancer. ErSO induced death of human PEO4 and Caov-3 ovarian cancer cells in vitro. In mouse xenografts, injected ErSO induced rapid complete, or near complete, regression of orthotopic metastatic PEO4 tumors and of Caov-3 ovarian tumors. Ovarian cancer patients often develop malignant ascites containing ovarian cancer organoids that drive metastasis. ErSO showed activity against 7/7 fresh patient derived ascites organoids (PDAOs). Low nanomolar ErSO destroyed 2/7 PDAOs. ErSO-mediated cell death in PDAOs occurred through the same a-UPR activation mechanism seen in cell culture. Moreover, ErSO family compound-induced a-UPR activation in ovarian cancer cells triggers necrotic cell death and release of damage associated molecular patterns (DAMPs), which strongly activated human macrophage and induced monocyte migration. These studies suggest ErSO has unusual potential for treatment of advanced ovarian cancer.

Ovarian cancer (OV) has the highest mortality rate among gynecological cancers. As OV progresses, tumor cells spread outside the ovaries to the peritoneal and abdominal cavities, forming cell clusters that float in the ascitic fluid caused by peritonitis carcinomatosa, leading to further dissemination and metastasis. These cell clusters are enriched with cancer stem cells (CSCs) which are responsible for treatment resistance, recurrence, and metastasis. Therefore, targeting CSCs is a potentially effective approach for treating OV. However, understanding how CSCs acquire treatment resistance and identifying targets against CSCs remains challenging. In this study, we demonstrate that 3D-spheroids of OV cell lines exhibit higher stemness than conventional adherent cells. Metabolomics profiling studies have revealed that 3D-spheroids maintain a high-energy state through increased glucose utilization in the citric acid cycle (TCA), efficient nucleotide phosphorylation, and elevated phosphocreatine as an energy buffer. We also found that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ production, is highly expressed in OV. Furthermore, the approach based on NAMPT dependence rather than histology found NAMPT to be a potential therapeutic target against CSCs, while also serving as a prognostic indicator in OV. Moreover, we identified a previously unrecognized anti-tumor mechanism whereby disulfiram, an aldehyde dehydrogenase (ALDH) inhibitor, synergistically inhibited mitochondrial function when combined with NAMPT inhibitors - leading to cell cycle arrest in G2/M. Finally, the combination of a NAMPT inhibitor and disulfiram showed significant anti-tumor effects and extended survival in an animal model. Our findings demonstrate the potential of spheroids as a preclinical model for targeting OV CSCs and also indicate that the combination of NAMPT inhibitors and disulfiram is a promising therapeutic strategy to overcome recurrent OV.

Background: Cytoreductive surgery (CRS), in combination with chemotherapy, is the main treatment for advanced-stage ovarian cancer. In vulnerable patients, this extensive surgery has a high complication risk and may lead to clinical decline. There is emerging evidence that prehabilitation could be valuable in optimizing the patient's condition prior to cytoreductive surgery, as is shown in colorectal surgery. However, there is limited evidence in gynecologic oncology. The objective of this study is to evaluate the feasibility and effects of implementing multimodal prehabilitation before cytoreductive surgery in patients with ovarian cancer. Methods: In two Dutch hospitals, 46 patients with ovarian cancer were included during the study period, of whom 32 participated in a multimodal prehabilitation program before CRS. The programs included at least physiotherapy, dietary advice and intoxication cessation. The timing, extent and content of the programs differed. Feasibility was assessed by eligibility and participation rates and adherence to the physiotherapy program. Effectiveness was measured by differences in functional capacity, postoperative outcomes and tolerance to adjuvant chemotherapy. Results: Eligibility rates in both hospitals were 83% and 89%, and participation rates were 68% and 72%. Adherence to the physiotherapy program was moderate and only satisfactory in 55% and 63% of the patients. All fitness endpoint measurements improved compared to the baseline. No significant differences in postoperative outcomes were found between prehabilitation and control patients. Prehabilitation patients appeared to have better tolerance to adjuvant chemotherapy, with fewer dose reductions (21% vs. 73%, p = 0.017) and dose deferrals (39% vs. 46%, not significant) compared to the control group. Conclusions: The implementation of multimodal prehabilitation before CRS is feasible and effective in patients with ovarian cancer with respectable eligibility and participation rates, along with improved functional capacity, even during neoadjuvant chemotherapy.

Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of this study is to assess age-specific differences in treatment and survival outcomes for ovarian cancer in women aged 70 years or older. Methods: This retrospective study included ovarian cancer patients treated at the Hospital del Mar, Barcelona, between 2016 and 2022. Patients were stratified into two groups: <70 and ≥70 years. Clinical and pathological data were analyzed, and hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS) were calculated using Cox proportional hazards regression models. Multivariate analysis was performed to compare outcomes. Results: A total of 110 patients were included (73 <70 years, 37 ≥70 years). Among the older group, 80.5% were diagnosed at advanced stages (III-IV), compared to 63% in the younger group (p = 0.012). Patients aged ≥70 were more likely to undergo interval surgery (p = 0.053) and receive non-standard treatment (p = 0.023). Complete cytoreduction was achieved in 95.8% of younger patients versus 81.3% of older patients (p = 0.024). Age ≥70 did not significantly impact DFS (p = 0.091), but OS was significantly worse in the older group (44.4% vs. 67.2%, p = 0.014). Conclusions: Older women (≥70 years) with ovarian cancer are more likely to be diagnosed at advanced stages, receive non-standard treatment, and achieve suboptimal cytoreduction compared to younger patients. While DFS was similar across age groups, older age was associated with worse OS, highlighting the need for age-tailored treatment strategies.

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of all ovarian cancer cases and contributing significantly to the high mortality rates associated with this disease. Because of the asymptomatic nature of early stage disease, most patients are diagnosed at advanced stages when the cancer has already spread into the abdominal cavity, requiring complex and intensive surgical and chemotherapeutic interventions followed by maintenance therapies. Although a minority of cases are associated with well defined genetic syndromes, specific risk factors and a clear etiology in many cases remain elusive. HGSOC tumors are characterized by a high frequency of somatic gene copy number alterations, often associated with defects in homologous recombination repair of DNA. All attempts to introduce an effective screening for HGSOC to date have been unsuccessful. This review elucidates the complexities surrounding HGSOC and encompasses its etiology, epidemiology, classification, pathogenesis, and the current array of treatment strategies. Understanding molecular underpinnings is crucial for the development of targeted therapies and personalized multimodal treatment approaches in centralized therapeutic structures. This review also examines the importance of the tumor microenvironment. In addition, the authors' objective is to underscore the critical importance of placing the patient's perspective and diversity at the forefront of therapeutic strategies, thereby fostering a genuinely participatory decision-making process and ultimately improving patient quality of life.

Since professional societies recommended counseling patients about opportunistic salpingectomy for ovarian cancer risk reduction, use of opportunistic salpingectomy has increased overall. However, physicians varied in their adoption of this new cancer prevention strategy.

To examine peer influence among physicians as a possible factor affecting their adoption of opportunistic salpingectomy at the time of hysterectomy.

Using insurance claims data from the Blue Cross Blue Shield Axis database across the United States, we identified female patients aged 18 to 49 who underwent an inpatient hysterectomy in 2019 to 2022. The outcome of interest was opportunistic salpingectomy, defined as complete removal of both (or the remaining) fallopian tubes without concurrent removal of the ovaries. We identified peer relationships among physicians based on whether 2 physicians billed for at least 2 of the same patients among insurance claims in 2017 to 2018. Then for each index physician performing inpatient hysterectomy in the 2019 to 2022 sample, we measured the rate of opportunistic salpingectomy among inpatient hysterectomies performed by all of their peer physicians in 2017 to 2018 (baseline). A multivariable regression analysis was used to examine whether an index physician's baseline exposure to peer physicians' opportunistic salpingectomy rate was associated with the subsequent use of opportunistic salpingectomy among their own patients in 2019 to 2022.

Among 3373 patients who underwent inpatient hysterectomy in 2019 to 2022 (operated on by 1528 index physicians), 1871 (55.5%) received opportunistic salpingectomy. The rate of opportunistic salpingectomy was higher among patients whose index physician had exposure to peer physicians with the highest or second highest quartile of baseline opportunistic salpingectomy rate (64.5% and 59.6%, respectively), compared to those with peer physicians in the lowest quartile of baseline opportunistic salpingectomy rate (44.0%) (P<.001). After adjusting for surgical indication, surgical route, and other patient/physician characteristics, having peer physicians in the highest and second highest quartile of baseline opportunistic salpingectomy rate was associated with a 1.99 (95% confidence interval, 1.46-2.71) times and 1.64 (95% confidence interval, 1.21-2.22) times higher odds of receiving opportunistic salpingectomy, respectively.

Sharing patients with other physicians who had high utilization of opportunistic salpingectomy was associated with an increased likelihood of an index physician subsequently using opportunistic salpingectomy at the time of hysterectomy. Future efforts to promote opportunistic salpingectomy use may explore the potential benefit of strategies leveraging physician peer influence.

Understanding the core principles of ovarian cancer has been significantly improved through the exploration of Ferroptosis, a type of cell death triggered by iron that leads to an increase in lipid peroxides. Current research has shed light on the critical functions of non-coding RNAs, such as circRNAs, lncRNAs, and miRNAs, in regulating ferroptosis in ovarian cancer. The aim of this paper is to comprehensively analyze how ncRNAs influence the development of ferroptosis in ovarian cancer cells. In-depth exploration is undertaken to understand the intricate ways in which ncRNAs regulate essential elements of ferroptosis, including iron management and lipid peroxidation levels. We also investigate their significant involvement in the progression of this type of cellular demise. It should be emphasized that ncRNAs can impact the synthesis of crucial proteins, such as GPX4, a key contributor to the cellular defense against oxidation, and ACSL4, involved in lipid formation. In addition, we examine the correlation between ncRNAs and well-known pathways associated with oxidative stress and cell death. The consequences of these discoveries are noteworthy, since focusing on particular ncRNAs could potentially render ovarian cancer cells more vulnerable to ferroptosis, effectively combating drug resistance problems. This discussion highlights the growing significance of ncRNAs in governing ferroptosis and their potential as useful biomarkers and treatment targets for ovarian cancer. We intend to promote additional research into the involvement of ncRNAs in controlling ferroptosis, based on current findings, with the ultimate goal of informing targeted therapeutic strategies and improving long-term treatment outcomes for individuals suffering from OC.

IntroductionDespite several studies in various cancers reporting a high prevalence of drug therapy problems (DTPs), there is a notable scarcity of comprehensive data addressing DTPs among patients with an ovarian cancer diagnosis. This study aimed to assess DTPs among those patients at Kenyatta National Hospital.MethodsA retrospective cohort study was used to assess the prevalence of DTPs among all 100 eligible patients with an ovarian cancer diagnosis. This research used a data abstraction tool to gather ovarian patients' data on drug therapy problems. The statistical package for Social Science version 20.0 software was used for data entry and analysis. The findings were presented using frequency tables, percentages and figures.ResultsThe mean age of the study population was 51.2 ± 15.1 with a bigger population being above 50 years (57.0%). The prevalent histological type of ovarian cancer was epithelial ovarian cancer (79.0%) followed by sex cord-stromal ovarian cancer (13%) and germ cell ovarian cancer (8%) which was least prevalent. A total of 175 DTPs were identified with the most prevalent being adverse drug reactions (40.6%) and drug non-adherence (17.1%). The number of medications used and stage of ovarian cancer as statistically significant predictors of DTP.ConclusionThe prevalence of DTPs was high and the most prevalent DTP was adverse drug reactions. The number of medications used and the stage of ovarian cancer were statistically significant predictors of DTP. Hence, regular medication reviews and robust pharmacovigilance systems should be implemented to detect and manage DTPs effectively.

Ovarian cancer (OC) usually progresses rapidly and is associated with high mortality, while a reliable clinical factor for OC patients to predict prognosis is currently lacking. Recently, the pathogenic role of neutrophils releasing neutrophil extracellular traps (NETs) in various cancers including OC has gradually been recognized. The study objective was to determine whether NETs-related biomarkers can be used to accurately predict the prognosis and guide clinical decision-making in OC. In this study, we utilized univariate and multivariate Cox regression to identify key prognostic features and developed a model with six NETs-related lncRNAs, selected via LASSO regression. The model's predictive capability was assessed through Kaplan-Meier, ROC, and Cox analyses. To understand the model's mechanisms, we conducted GO term analysis, KEGG pathway enrichment, and GSEA. We also analyzed gene mutation status, tumor mutation load, survival rates, and model correlation. Additionally, we compared immune functions, immune checkpoint expression, and chemotherapy sensitivity between risk groups. Besides, we validated the model's predictive value using test data and tissues acquired from our institution. Finally, we performed in vitro and in vivo experiments to confirm the expression of model lncRNAs and the cellular level function of GAS5. We developed a model using six NETs-associated lncRNAs: GAS5, GBP1P1, LINC00702, LINC01933, LINC02362, and ZNF687-AS1. The model's predictive performance, evaluated via ROC curve, was compared with traditional clinicopathological features. GO process analysis highlighted molecular functions related to antigen binding and immune system biological processes. Variations were observed in transcription regulators affecting immune response, inflammation, cytotoxicity, and regulation. We also predicted IC50 values for chemotherapeutic drugs (bexarotene, bicalutamide, embelin, GDC0941, and thapsigargin) in high- and low-risk groups, finding higher IC50 values in low-risk patients. The risk model's robustness was validated using OC cells, tissues, and clinical datas.

Epithelial-mesenchymal transition (EMT) plays critical roles in tumor progress and treatment resistance of ovarian cancer (OC), resulting in the most deadly gynecological cancer in women. However, the cell-intrinsic mechanism underlying EMT in OC remains less illuminated.

SKOV3, the OC cell line, was treated with TGF-β to induce EMT or with SB431542, an inhibitor of the TGF-β signaling pathway, to reduce migration. The function of HBO1 in EMT was confirmed by knock-down or overexpression of HBO1 in SKOV3 cells. The role of HBO1 in cell proliferation and apoptosis of SKOV3 cells was analyzed by flow cytometry. The whole-genome transcriptome was used to compare significantly different genes in control and HBO1-KD SKOV3 cells. T-cell cytotoxicity assays were measured by an IVIS spectrum. The chromatin binding of HBO1 was investigated using CUT&Tag-seq.

Here, we show that HBO1, a MYST histone acetyltransferase (HAT), is a cell-intrinsic determinant for EMT in OC cells. HBO1 is greatly elevated during TGF-β-triggered EMT in SKOV3 OC cells as well as in later stages of clinical OC samples. HBO1 Knock-down (KD) in SKOV3 cells blocks TGF-β-triggered EMT, migration, invasion and tumor formation in vivo. Interestingly, HBO1 KD in SKOV3 cells suppresses their resistance to CAR-T cells. Mechanistically, HBO1 co-binds the gene sets responsible for EMT with SMAD4 and orchestrates a gene regulatory network critical for tumor progression in SKOV3 cells.

HBO1 plays an essential onco-factor to drive EMT and promote the immunotherapy resistance in ovarian cancer cells. Together, we reveal a critical role of HBO1 mediated epigenetic mechanism in OC progression, providing an insight into designing new therapy strategies.

The COVID-19 pandemic has significantly impacted healthcare-seeking behaviors, leading to delayed cancer diagnoses due to hospital-related anxiety. This case highlights the severe consequences of delayed medical consultation in a patient with advanced ovarian cancer. A 47-year-old female presented with severe abdominal distension, massive ascites, and extensive abdominal wall necrosis after avoiding medical care for months due to severe hospital-related anxiety, exacerbated by the loss of her husband during the COVID-19 pandemic. On admission, a CT scan could not be performed due to the patient's inability to lie supine and extreme abdominal distension. To relieve pressure and improve respiratory function, an abdominal drain was inserted, releasing 72 L of ascitic fluid over five days. Following drainage, imaging confirmed a large ovarian tumor with peritoneal involvement, and a multidisciplinary team (surgeons, gynecologists, plastic surgeons, anesthetists, and intensive care specialists) determined the need for surgical intervention. Histopathology confirmed mucinous adenocarcinoma with pseudomyxoma peritonei (FIGO IIIB). This case underscores the critical impact of delayed oncological diagnosis and the need for enhanced patient education, mental health support, and structured screening programs to prevent similar late-stage presentations.

The unfolded protein response (UPR) is crucial in maintaining cell survival during stressful conditions, but prolonged ER stress can lead to apoptosis. Based on the evidence acquired, it has been suggested that inhibiting the protein kinase RNA-like ER kinase (PERK) pathway, which constitutes an adaptive branch of UPR, may represent a viable approach for impeding the proliferation of neoplastic cells. This study assesses the influence of PERK inhibition mediated by miR-204-5p on the growth of ovarian cancer cell lines, OVCAR3 and SKOV3. We demonstrated that miR-204-5p significantly downregulated the expression of PERK at the RNA and protein levels. The suppression of PERK, mediated by miR-204-5p, significantly diminished cellular viability and enhanced apoptotic cell death in cells exposed to Tunicamycin (Tm). We ascertained that the inhibition of PERK by miR-204-5p decreased eukaryotic initiation factor 2alpha (eIF2α) phosphorylation. Moreover, activating transcription factor 4 (ATF4) and CCAAT-enhancer-binding homologous protein (CHOP) expression levels were notably elevated in response to miR-204-5p. The expression of Bax and caspase-12 was found to be upregulated, while the expression of Bcl-2 was reduced. This study is the first to demonstrate that silencing the PERK gene through miR-204-5p significantly inhibits cell growth and promotes ER-stress-induced apoptosis in ovarian cancer cells.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has shown promise in preclinical models to selectively eliminate drug-resistant micrometastases that evade standard treatments. Moreover, taPIT has the potential to resensitize chemo-resistant tumor cells to chemotherapy, making it a complementary modality for treating recurrent high-grade serous ovarian cancer (HGSOC). However, the established implementation of taPIT relies on the overexpression of EGFR in tumor cells, which is not universally observed in HGSOCs. Motivated by the need to expand taPIT applications beyond EGFR, we conducted mRNA-sequencing and proteomics to identify alternative cell surface targets for taPIT in patient-derived HGSOC cell cultures with weak EGFR expression and lacking expression of other cell surface proteins commonly reported in the literature as overexpressed in ovarian cancers, such as FOLR1 and EpCAM. Our findings highlight TFRC and LRP1 as promising alternative targets. Notably, TFRC was overexpressed in 100% (N = 5) of the patient-derived HGSOC models tested, whereas only 60% of models had high EpCAM expression, suggesting that future larger cohort studies should include TFRC. While this study focuses on target identification, future work will expand the approaches developed here to larger HGSOC biopsy repositories and will also develop and evaluate antibody-photosensitizer conjugates targeting these proteins for taPIT applications.

High-grade serous ovarian carcinoma (HGSOC) is the deadliest gynecologic cancer. Key to the progression and ultimate lethality of this subtype is the intra-tumoral heterogeneity, which is defined as the coexistence of different cell types and populations within a single tumor. Among those, ovarian cancer stem cells (OCSCs) are a distinct subpopulation of tumor cells endowed with stem-like properties, which can survive current standard therapies, resulting in tumor recurrence. Here, we generated ex vivo primary OCSC-enriched three-dimensional (3D) spheres from 10 distinct treatment naive patient-derived adherent (2D) cultures. We used state-of-the-art quantitative mass spectrometry to characterize the molecular events associated with OCSCs by analyzing their proteome and phosphoproteome. Our data revealed a stemness-related protein signature, shared within a heterogeneous patient cohort, which correlates with chemo-refractoriness in a clinical proteomics dataset. Moreover, we identified targetable deregulated kinases and aberrant PDGF receptor activation in OCSCs. Pharmacological inhibition of PDGFR in adherent OC cells reduced the stemness potential, measured by sphere formation assay. Overall, we provide a valuable resource to identify new OCSC markers and putative targets for OCSC-directed therapies.

Background/Objectives: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, largely due to the challenges of early detection. While next-generation sequencing (NGS) has been explored for screening, its high cost limits large-scale implementation. To develop a more accessible diagnostic solution, we designed a qPCR-based algorithm optimized for early OC detection, with a focus on high-grade serous ovarian cancer (HGSOC), the most aggressive subtype. Methods: Peripheral blood samples from 19 ovarian cancer patients, 37 benign tumor patients, and 34 asymptomatic controls were analyzed using RNA sequencing to identify splice junction-based biomarkers with minimal expression in benign samples but elevated in OC. Results: A final panel of 10 markers was validated via qPCR, demonstrating strong agreement with sequencing data (R2 = 0.44-0.98). The classification algorithm achieved 94.1% sensitivity and 94.4% specificity (AUC = 0.933). Conclusions: By leveraging platelet RNA profiling, this approach offers high specificity, accessibility, and potential for early OC detection. Future studies will focus on expanding histologic diversity and refining biomarker panels to further enhance diagnostic performance.

The clinical prognostic factors for ovarian clear cell carcinoma (OCCC) are limited, and we aim to construct a model to predict the survival of OCCC patients.

Data were extracted from the SEER database for patients diagnosed with OCCC. Cox regression analyses were used to identify independent risk factors for OCCC. Two nomograms were developed, and the results were evaluated comprehensively by C-index, ROC curve, calibration curve, and DCA curve. Patients diagnosed with OCCC were used as the validation set to verify the model.

A total of 1855 OCCC patients from the SEER database were used as the training set, and 101 patients from our hospital were used as the validation set. Cox regression analysis of the independent risk factors affecting the prognosis of OCCC was used to construct nomograms. The C-index of the training set OS was 0.76, and the validation set OS was 0.75. The AUC of the training set OS is 0.803, 0.794, and 0.802 for 1, 3, and 5 years, and 0.774, 0.800, and 0.923 for the validation set. The calibration curve and DCA curve also showed that OS and CSS have good predictive power.

A nomogram based on 8 prognostic factors analyzed by Cox regression can predict the prognosis of OCCC patients effectively.

Ovarian cancer (OC) is one of the most common cancers in women. Biomarkers for OC are still being sought. The aim of this review was to evaluate microRNAs in the prognosis and diagnosis of OC. We conducted a literature review searching for articles published from January 2014 to September 2024. We included articles presenting the association of microRNAs with ovarian cancer prognosis, where patient survival was shown by the Kaplan-Meier curve, and articles presenting the association of microRNAs with ovarian cancer diagnosis, where the results were presented as an ROC curve. MicroRNAs are promising clinical markers in ovarian cancer patients. As is shown here, expression (high or low) of various miRNAs was differentially associated with survival in OC patients, with some miRNAs being associated with a longer survival and some with a shorter survival. In the absence of diagnostic markers for OC, the raised role of miRNAs in diagnosis seems all the more important. The diagnostic value of miRNAs has been shown, mostly as blood biomarkers, although they have also been evaluated as tissue or urine markers. MiRNAs have an important role as clinical biomarkers for ovarian cancer, not only as single molecules, but also as biomarker pairs or panels of miRNAs. It should be noted that most of the miRNAs reviewed here have been studied once, so despite the promising results, it seems necessary to conduct studies to confirm or negate the results obtained.

To demonstrate the significance of supercharged natural killer (sNK) cells to target aggressive gynecological tumours.

We used cell cultures of peripheral blood-derived mononuclear cells (PBMCs) and purified NK cells alone and in the presence of tumours. MHC-class gene expression assessments of ovarian tumours were performed using gene set enrichment analysis (GSEA). Secretion and expression levels of cytokines in PBMCs and NK cells were determined using ELISA and scRNA seq analysis, respectively. A flow cytometer was used for surface marker analysis. 51Cr and eSight were used to determine the killing activity of NK cells.

We have observed a significant decrease in the numbers and functions of NK cells in patients with ovarian cancer. GSEA revealed differently expressed genes, decreased differentiation- and immune-related genes, and increased genes for cell cycle analysis in recurrent tumours compared with chemo-naive ovarian tumours. Increased gene expression as well as secretion of interferon-γ and tumour necrosis factor-α and increased avidity in binding to tumour cells by sNK cells was observed. Unlike primary interleukin (IL)-2-activated NK cells, sNK cells effectively lysed OVCAR8 ovarian poorly differentiated cancer stem-like cells (PDCSCs) and well-differentiated OVCAR4 tumours. Primary ovarian tumours with lower MHC-class I expression were highly susceptible to both primary IL-2-activated NK and sNK cells, whereas the well-differentiated tumours with high expression of MHC-class I were only susceptible to sNK cells.

The use of sNK cells in immunotherapy emerges as a potentially effective strategy to target and eliminate the majority of ovarian tumour clones, thereby providing a potential therapeutic opportunity in preventing the recurrence of the disease.

New three-dimensional (3D) augmented reality technology represents an opportunity to improve presurgical planning. This study aimed to measure the accuracy of 3D volumetric rendering on augmented reality headsets to predict extent of disease prior to ovarian cancer cytoreductive surgery.

This single-institution prospective study took place from 03/01/2024 to 10/01/2024. Utilizing Medivis 3D augmented reality headsets, investigators reviewed volumetric renderings for patients with suspected advanced ovarian cancer prior to scheduled surgery and filled out a survey predicting presence of disease based on anatomic site. Pathology records were later reviewed to confirm the presence of disease. Statistical analyses included Cohen's kappa coefficient, sensitivity/specificity, and positive/negative predictive value measurements.

We included 15 patients: 9 (60 %) with interval cytoreduction and 6 (40 %) with primary cytoreduction. For procedure, 14 (93 %) had complete gross resection and 1 (7 %) suboptimal cytoreduction (>1 cm of residual disease). Using pathology results as the gold standard for each anatomic site, the 3D headset demonstrated accuracy of 100 % for omentum and pelvic lymph nodes; 93 % for para-aortic lymph nodes, right diaphragm, rectum, and liver; 87 % for small mesentery; and 80 % for small bowel serosa, spleen, and left diaphragm (P > 0.05 for all).

The use of preoperative 3D volumetric rendering on augmented reality headsets to predict the extent of ovarian cancer spread showed high agreement with pathology across all anatomic sites studied. Additional research is needed to assess the potential role of this technology in improving surgical planning and patient outcomes.

Numerous secreted bacterial metabolites were identified with bioactivity in various neoplasias, including ovarian cancer. One such metabolite is ursodeoxycholic acid (UDCA), a secondary bile acid that has widespread beneficial effects in neoplasias. Hereby, we assessed the bioactivity of UDCA in cell models of ovarian cancer, by applying UDCA in concentrations corresponding to the serum reference concentrations of UDCA (300 nM). UDCA induced epithelial-to-mesenchymal transition (EMT), increased the flux of glycolysis and reduced the naturally occurring oxidative stress in ovarian cancer cells. These changes were dependent on the activation of NRF2. The tumoral overexpression of UDCA-induced genes in humans correlated with worse survival. These results point out that bacterial metabolites may have opposite effects in different neoplasias and raise the possibility that UDCA-containing remedies on the long run may support cancer progression in ovarian cancer patients.