Search Results (484)

Background and Objectives: Advanced-stage epithelial ovarian cancer (EOC) is associated with poor prognosis, with complete macroscopic cytoreduction representing the strongest modifiable predictor of survival. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative to primary debulking surgery (PDS) in patients with high tumor burden. However, its impact on surgical complexity remains debated. This study aimed to compare operative characteristics and survival outcomes between NACT + IDS and PDS using standardized scoring metrics in a real-world oncologic setting. Materials and Methods: We retrospectively analyzed 47 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV high-grade serous EOC treated between January 2018 and August 2022 at a single tertiary center. Twenty-five patients received platinum–taxane-based NACT followed by IDS, and twenty-two underwent upfront PDS with adjuvant chemotherapy. Surgical effort was quantified using the Surgical Complexity Score (SCS), and intra-abdominal tumor burden was assessed via the Peritoneal Cancer Index (PCI). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Hazard ratios (HRs) with 95% confidence intervals were derived from Cox proportional hazards models. Results: Complete cytoreduction (R0) was achieved in 76% of the NACT + IDS group and 68% of the PDS group. Mean surgical complexity and operative time were significantly lower following NACT (SCS 5.0 vs. 6.2, p = 0.04; 140 vs. 197 min, p = 0.001), without significant differences in blood loss, complication rates, or length of hospital stay. Median PFS was 25 months in the NACT + IDS group versus 21 months in the PDS group, and the difference was not statistically significant. Among patients with R0 resection, survival outcomes were comparable between treatment arms. Conclusions: NACT + IDS was associated with shorter and less complex surgeries in selected patients, but survival outcomes appeared similar when R0 was achieved. Data suggest that selective use of NACT in patients with extensive disease burden or limited general health status may be suitable, while confirming that complete cytoreduction remains the most critical prognostic factor, although these survival comparisons are exploratory given the retrospective design and limited sample size. Full article

Objective: The objective of this paper is to define “poor candidates” and to conduct an analysis of preoperative selection criteria, considering factors related to the patient, tumor burden, and histopathological characteristics, in the case of patients with advanced epithelial ovarian cancer (EOC) FIGO III-IV with a low probability of optimal cytoreduction. Methodology: The authors of this narrative review conducted an analysis of articles published over a 20-year period (2005–2025), with the following selection criteria for the topics of the papers: advanced epithelial ovarian cancer (FIGOIII-IV), surgical indications in advanced ovarian cancer, poor candidates for surgery, and dependence between surgery and histopathologic and molecular type of EOC. They used using PubMed, Science Direct, and Scopus as databases. The results of the analysis were organized into three large chapters that grouped patient-related factors, tumor burden-specific factors, and histopathological criteria. Results: The authors identify a series of criteria with a high risk of unfavorable postoperative evolution, which led to delayed chemotherapy treatment and suboptimal management. These criteria are related to the patient’s field (ECOG > 3, Charlson Comorbidity Index (CCI) > 2, BMI > 25–30, hypoalbuminemia, hypokalemia), imaging or intraoperative factors predictive for residual tumor, and histopathological or genetic factors (presence of BRCA mutation favors optimal cytoreduction even in cases with high tumor burden; in the case of low-grade serous ovarian carcinoma, surgical intervention is recommended even if there are suboptimal resection criteria, accepting resection > 1 cm due to the poor response to specific chemotherapy treatment). Conclusions: Considering all these aspects, patient selection for primary debulking surgery (PDS) or NACT (neoadjuvant chemotherapy) and interval debulking surgery (IDS) should be conducted in oncological surgery centers highly specialized in gynecological neoplasms, thus ensuring an optimal therapeutic pathway for patients with EOC. Full article

ELK1 is a Transcription factor (TF) belonging to the ETS-domain TF family, mainly activated via RAS-RAF-MEK-ERK signaling. As a nethermost pathway molecule, ELK1 binds to Serum-response elements (SREs) and directly regulates the transcription of Immediate early genes (IEGs) including FOS and EGR1. Due to ELK1’s influence on key cellular processes such as proliferation, migration, apoptosis evasion, and Epithelial-to-mesenchymal transition (EMT), its role as a key contributor to tumorigenesis is emerging. In recent years, elevated expression and/or activation of ELK1 has been reported in various malignancies, including lung, breast, prostate, colorectal, blood, gastric, liver, cervical, thyroid and ovarian cancer. ELK1 acts primarily through direct DNA binding but also through interaction with other oncogenes, noncoding RNA molecules, TFs, and upstream kinases (other than ERK1/2), thus participating in diverse axes of transcriptional regulation. Its crucial role in IEG expression has been particularly implicated in cancer progression, metastasis, and drug resistance. Owing to its role in multiple cellular functions and its subsequent oncogenic potential, further elucidation of intracellular ELK1 interactions is of paramount importance. This review aims to summarize current evidence on ELK1’s involvement in solid tumors, dissect reported mechanistic roles, and highlight recent insights that could fuel future ventures of high translational interest. Full article

Background: It is difficult to make a definite diagnosis of borderline epithelial ovarian tumors before surgery. In order to avoid incorrectly classifying tumors as benign, a differential diagnosis model was developed to distinguish between benign and borderline epithelial tumors utilizing multimodal information. Method: A multicenter study was conducted. A retrospective analysis of the transvaginal ultrasonography and clinical data of patients who underwent surgery and received pathological diagnoses of borderline and benign epithelial ovarian tumors was conducted. Both Univariate and multivariate logistic regression analyses were used to develop a diagnostic model for borderline epithelial tumors. The efficacy and feasibility of this model were assessed through examination of training, internal validation, and external test sets. Results: There was a significant difference in D-dimer levels between borderline and benign epithelial tumors. Abnormal CA125, D-dimer, maximum mass diameter > 10 cm, regular and irregular solid portions, and blood flow in the mass were independent risk factors for borderline epithelial ovarian tumors. The diagnostic model was evaluated by the Hosmer–Lemeshow test and demonstrated strong fitting capabilities. ROC curve analysis of the training set, verification set, and external test set confirmed the model’s predictive ability. Conclusions: These independent risk factors may be combined to assess the risk of borderline epithelial ovarian tumors. Our findings will assist novice gynecologic sonographers in distinguishing between benign and borderline epithelial tumors. Full article

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a key regulator of cancer stem cell (CSC) biology and signaling. In CSCs, ROR1 acts as a receptor or co-receptor, interacting with non-canonical WNT ligands, and forming complexes with proteins like CD19 and HER2, to activate diverse downstream signaling pathways. ROR1 signaling in CSCs promotes proliferation, maintains stemness, and enhances migration, invasion, and the epithelial-to-mesenchymal transition (EMT). While minimally expressed after embryogenesis, ROR1 is aberrantly upregulated in numerous cancers, including ovarian, breast, pancreatic, and hematologic malignancies. ROR1 overexpression drives tumor progression, resistance to chemotherapies, disease recurrence, and ultimately metastasis. This expression pattern positions ROR1 as a promising target for CSC-specific therapies. High ROR1 expression is consistently linked to aggressive disease and poor patient outcomes. Here, we review ROR1′s role in CSCs and highlight the complex signaling that is observed in the CSC population. Further, we evaluate the gaps in the current understanding of ROR1 signaling in CSCs and describe how ROR1 regulates the associated signaling pathways. Finally, we provide an up-to-date summary of the promising therapeutic strategies targeting ROR1 that overcome conventional cancer treatment limitations. This review highlights the role of ROR1 as a critical, functional driver of CSCs and adverse patient outcomes across various malignancies. Full article

Folate receptor alpha (FRα) is a high-affinity folate transporter overexpressed in various epithelial malignancies, particularly high-grade serous ovarian carcinoma. Given its restricted expression in normal tissues and accessibility in tumors, FRα is an emerging therapeutic target. Immunohistochemistry (IHC) is the standard method for FRα assessment; however, interpretation is semi-quantitative and prone to interobserver variability. This study aimed to evaluate interobserver agreement among 12 pathologists in the IHC assessment of FRα in ovarian cancer, focusing on internal control adequacy, staining intensity, and the percentage of FRα-positive tumor cells. Thirty-seven high-grade serous ovarian carcinoma cases were stained using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. A reference panel of four expert pathologists established consensus diagnoses. Twelve pathologists independently assessed the slides, recording internal control adequacy, staining intensity (positive vs. negative), and percentage of FRα-positive tumor cells. Interobserver agreement was measured using Fleiss’ kappa and intraclass correlation coefficient (ICC). Agreement on internal control adequacy was almost perfect (κ = 0.84). Substantial agreement was observed for staining intensity (κ = 0.76), while percentage estimation showed almost perfect concordance (ICC = 0.89). Discrepancies were primarily confined to borderline cases (65–85% positivity) and tumors with intermediate staining, reflecting interpretive challenges near clinical decision thresholds. Pathologists demonstrated high reproducibility in FRα IHC assessment, particularly in estimating percentage positivity and control adequacy. These findings support the clinical utility of FRα IHC but underscore the need for standardized scoring criteria and potential integration of digital tools to enhance consistency, especially in borderline cases. Full article

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

Ovarian cancer is a deadly gynecological malignancy that will affect about 21,000 women and result in almost 153,000 deaths in the United States in 2025. New clinical tools that facilitate early diagnosis and treatment of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. We utilized a previously identified single-strand DNA aptamer RLA01 that binds and internalizes into target epithelial ovarian cancer cells to label PLGA-based nanoparticles and determine their ability to selectively target EOC cells and deliver payloads for cellular internalization. Nanoparticles labeled with RLA01 significantly enhanced cellular uptake 20–85% by receptor-mediated endocytosis into target EOC Caov-3 cells and inhibited cellular uptake in non-target HOSE 6-3 cells. Further, labeling of paclitaxel-loaded nanoparticles with RLA01 significantly decreased cell proliferation and induced apoptosis. A preliminary pilot study looking at the in vivo stability of aptamers demonstrated their ability to promote retention and honing of nanoparticles at tumors. These data demonstrate the effective combinatorial use of aptamer RLA01 and nanoparticle technologies for the direct targeting of tumor cell populations both in vitro and in vivo. Full article

Background/Objectives: Endometriosis and high-grade serous ovarian cancer (HGS-OC) share common features within the peritoneal immune microenvironment, yet they exhibit divergent clinical outcomes. This study aimed to dissect the immune–metabolic landscape of the peritoneal cavity in patients with endometriosis and ovarian cancer by evaluating macrophage polarization, intracellular signaling pathways, and iron-driven oxidative stress. Methods: A prospective cohort study enrolled 40 patients with endometriosis, 198 with ascitic ovarian cancer (178 HGS-OC), and 200 controls with benign gynecological conditions. Peritoneal and peripheral blood samples were analyzed via flow cytometry for macrophage (M1/M2) polarization markers, mTOR/AKT expression, and glucose uptake. Inflammatory markers (IL-6, CRP), oxidative stress (ROS), and iron metabolism parameters (hepcidin, ferritin, transferrin, serum/free iron) were quantified. Results: HGS-OC displayed a predominance of M1-polarized tumor-associated macrophages (TAMs) (CD14⁺/CD80⁺/Glut1⁺) and a high M1/M2 ratio (2.5 vs. 0.8 and 0.9; p = 0.019), correlating positively with IL-6 (p = 0.015), ROS (p = 0.023), hepcidin (p = 0.038), and ferritin (p = 0.043). Conversely, endometriosis showed a dominant M2 profile (CD14⁺/CD163⁺), elevated intracellular mTOR and AKT expression in both TAMs and epithelial cells (p < 0.01), and significantly higher ascitic ROS and free iron levels (p = 0.047 and p < 0.0001, respectively). In endometriosis, the M1/M2 ratio correlated inversely with free iron (p = 0.041), while ROS levels were directly associated with iron overload (p = 0.0034). Conclusions: Endometriosis exhibits a distinct immune–metabolic phenotype characterized by M2 macrophage predominance and iron-induced oxidative stress, contrasting with the inflammatory, M1-rich profile of HGS-OC. These findings suggest that iron metabolism and macrophage plasticity contribute to disease persistence in endometriosis and may inform future immunomodulatory strategies. Full article

Ovarian cancer, the most lethal form of gynecological cancer worldwide with a poor prognosis, is largely driven by an immunosuppressive tumor microenvironment. In this study, we investigated the anticancer effects of hydnocarpin, a natural flavonolignan derived from the flowers of Pueraria lobata, focusing on its effects on ovarian cancer and tumor-associated immune cells, including ovarian cancer-stimulated macrophages (MQs) and T cells. Hydnocarpin exhibited potent cytotoxicity against multiple ovarian cancer cell lines but only minimal toxicity against normal ovarian surface epithelial cells. Mechanistically, hydnocarpin triggered caspase-dependent apoptosis, as evidenced by the activation of caspase-9 and -3, with limited involvement of caspase-8, indicating the activation of the intrinsic apoptotic pathway. Experimental data implicated reactive oxygen species generation as a key mediator of hydnocarpin cytotoxicity, and reactive oxygen species inhibition significantly inhibited this cytotoxicity. In addition to its direct tumoricidal effects, hydnocarpin reprogrammed the tumor-associated immune cells, ovarian cancer-stimulated macrophages and T cells, by downregulating the levels of M2 MQ markers and pro-tumoral factors (matrix metalloproteinase-2/9, C–C motif chemokine ligand 5, transforming growth factor-β, and vascular endothelial growth factor) and enhancing MQ phagocytosis. Additionally, hydnocarpin promoted T-cell activation (interferon-γ and interleukin-2) and reduced the expression levels of immune evasion markers (CD80, CD86, and VISTA). Overall, this study demonstrated the dual anti-tumor effects of hydnocarpin on both ovarian cancer cells and immunosuppressive immune components in the tumor microenvironment, highlighting its potential as a novel therapeutic candidate for ovarian cancer. Full article

Objectives: The current study underscores the potential role of miRNAs, specifically miR-3173 and miR-155, as promising biomarkers for breast and ovarian cancers (BC and OC). The primary objective was to evaluate the expression levels of these miRNAs in cancer patients compared to healthy individuals, assess their diagnostic accuracy, and explore their associations with cancer progression and prognosis. Methods: This study involved 60 participants, comprising 30 patients diagnosed with primary BC and 30 patients with epithelial ovarian cancer (EOC). Tumor tissue samples were obtained from all patients for molecular analysis. For control comparisons, adjacent non-tumorous tissues from both groups were utilized. miR-3173 and miR-155 expression levels were measured using real-time PCR (qPCR). The diagnostic accuracy of both miRNAs was evaluated through receiver operating characteristic (ROC) curve analysis, calculating sensitivity and specificity for distinguishing cancer cases from healthy controls. Additionally, the association of miR-155 with metastasis was explored, and miR-3173’s correlation with poor progression-free survival in BC patients was assessed using Kaplan–Meier survival curve analysis. Results: Both miRNAs were found to be significantly upregulated in cancer patients compared to healthy individuals, with miR-155 exhibiting high sensitivity and specificity for distinguishing BC and OC cases. Notably, miR-155 is associated with metastasis, which aligns with previous research, suggesting its role as an oncogene in epithelial OC. Meanwhile, the elevated expression of miR-3173 correlates with poor progression-free survival in BC patients, marking it as a potential prognostic marker. However, these results highlight the complexity of miRNA expression in cancer progression, as miR-3173 showed varied associations with different types of cancer. Despite these challenges, the ROC curve analysis for both miRNAs is promising with high sensitivity and specificity for both BC and OC. Conclusion: The study findings are particularly significant in the context of early diagnosis and monitoring cancer progression, yet further investigations involving larger cohorts and diverse populations are needed to validate these results. Future studies should focus on expanding sample sizes, refining the understanding of miRNA roles in tumor progression, and exploring their potential as therapeutic targets. These advancements could significantly enhance personalized treatment strategies for breast and ovarian cancer, improving patient outcomes. Full article

Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Background/Objectives: Bowel resection may be necessary during cytoreductive surgery (CS) in advanced epithelial ovarian cancer to achieve complete tumor removal. However, concerns about increased perioperative risks and unclear survival benefits have led to ongoing debate. This study aimed to evaluate the impact of bowel resection on perioperative mortality and overall survival (OS) in patients undergoing CS. Methods: We retrospectively reviewed 127 patients with FIGO stage IIB–IV epithelial ovarian cancer who underwent primary or interval CS between 2007 and 2021. Patients were stratified based on the performance of bowel resection. Clinical, surgical, and survival data were analyzed using Kaplan–Meier survival analysis and Cox proportional hazards modeling. Primary outcomes were 90-day mortality and OS. Results: Bowel resection was performed in 58 patients (46%) with more extensive disease and poorer ECOG performance scores. Although the resection group had increased perioperative risks (e.g., higher transfusion rates and ICU use), OS was similar between groups (log-rank p = 0.122). Multivariate analysis identified that increasing age (HR = 1.042, p = 0.005) was independently associated with poorer OS, whereas lymph node dissection (HR = 0.450, p = 0.003) and undergoing primary CS (HR = 0.540, p = 0.047) were associated with improved survival. Bowel resection was not independently associated with OS. Conclusions: Bowel resection does not adversely affect OS when optimal cytoreduction is achieved. Although it increases perioperative complexity, it can be safely incorporated into CS in selected patients. These findings support its use as part of an individualized surgical strategy for advanced ovarian cancer. Full article

The hedgehog pathway is a major regulator of cell growth and differentiation during embryogenesis and early development. The literature suggests that variations in this pathway’s genes play a role in tumor progression and response to therapy. This study aimed to assess the correlation between the expression levels of selected genes of this pathway and the progression-free and overall survival of ovarian cancer patients. Using the database Kaplan–Meier plotter, which includes the gene expression and survival data of 1565 ovarian cancer patients, higher expression levels of the genes SHH, PTCH1, PTCH2, and GLI1 displayed better survival correlations, while GLI, GLI3, and SUFU correlated with adverse outcomes. Further dissection revealed a differential impact of the genes in specific clinical-histopathological categories. Notably, higher expression levels of SUFU were associated with a negative impact on ovarian cancer patients under many clinical–histopathological aspects. These results shed new light on the role of these genes in the chemoresponsiveness of ovarian cancer, especially SUFU, which could be considered a novel indicator for poor prognosis in epithelial ovarian cancer. Full article