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Introduction Ovarian cancer is a leading cause of cancer mortality globally due to late-stage diagnosis and limited treatment options. PARP inhibitors have shown promise as effective treatments for recurrent and various stages of ovarian cancer. Aim of the Study This study reviews the efficacy and application of PARP inhibitors in ovarian cancer treatment over the past 15 years, focusing on literature from the PubMed database post-2009 and considering FDA and EMA guidelines. Review methods A literature review was conducted using the PubMed database, focusing on studies published after 2009. The review also incorporated recommendations from the FDA and the European Medicines Agency regarding the use of PARP inhibitors in ovarian cancer treatment. Results The findings highlight the substantial impact of PARP inhibitors on ovarian cancer treatment, improving PFS and overall outcomes. Olaparib, niraparib, and rucaparib have become integral to ovarian cancer management, offering effective options for patients with BRCA mutations or homologous recombination deficiencies. These inhibitors have been validated in multiple clinical trials, underscoring their robustness and effectiveness. Combination therapies, such as olaparib with bevacizumab, further enhance therapeutic outcomes, showcasing the potential for synergistic effects. Summary PARP inhibitors represent a significant advancement in ovarian cancer treatment, offering improved survival outcomes for patients with specific genetic profiles. Their integration into standard care protocols underscores their importance and efficacy, providing valuable therapeutic options in the fight against ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Among all the gynaecologic malignancies, ovarian cancer (OV) has the highest mortality rate, and herbal plants have been regarded as an alternative strategy for ovarian cancer therapy. Accumulating evidence indicates that the aboveground part of Eclipta prostrata (L.) L., known as Ecliptae Herba (EH), has anti-cancer activity and can contribute to the management of gynaecological disorders treatment. However, the application and the mechanism of EH against OV remain unexplored. Methods: A cell proliferation assay was first performed to validate the inhibitory effect of EH extracts on ovarian cancer cells. Network pharmacology was then employed to recognize potential bioactive compounds and target genes of EH. A Venn diagram was built to obtain the common targets of EH and OV and the protein-protein interaction (PPI) network of EH-OV correlated target genes was established by STRING. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment approaches were adopted to further reveal the molecular mechanism. Drug-compound-target-pathwaydisease network of EH in OV treatment was constructed. The expression of the predicted targets, cell cycle changes and cell apoptosis levels were analyzed to confirm the predicted mechanism of EH. Results: EH extracts suppressed the proliferation of human ovarian cancer cells in a concentration- and time-dependent manner. Ten bioactive compounds and 290 compound-associated targets were collected for EH-OV common targets exploration. A total of 74 EH-OV correlated genes were gathered and enrichment analysis identified phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathway as the main machinery. Drug-compound-target-pathway-disease network indicated the polypharmacological effect of EH. Finally, EH extracts were confirmed to inhibit cell proliferation and induce cell apoptosis of ovarian cancer cells by inactivating PI3K/AKT signaling pathway. Conclusions: This study demonstrated the anti-ovarian cancer activity of whole EH extracts and indicated that EH should be considered as a potential therapeutic strategy for ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is a prevalent form of gynecological malignancy. Abnormal expression of SHC-adaptor protein (SHC) binding and spindle-associated protein 1 (SHCBP1) is reported critical in various cancers, whereas its role in OC is unknown. Here we investigated the function of SHCBP1 in OC. Methods: The expression of SHCBP1 in OC and the survival probability of OC patients were analysed using bioinformatics. Cell growth was evaluated by Cell Counting Kit-8 (CCK-8) as well as colony formation. Cell motility was examined using the wound-healing and Transwell assays. The stemness of OC cells stemness was evaluated through sphere formation assay. Key factors associated with the wingless (Wnt)/β-catenin axis were analysed using Immunoblot. The expression of SHCBP1 was elevated in OC, and SHCBP1 was associated with the survival probability of OC patients. Results: Silencing SHCBP1 suppressed the proliferation of SKOV3 as well as A2780 cells, as well as their migration and invasion. Additionally, knockdown of SHCBP1 impaired the stemness of OC cells. Furthermore, SHCBP1 knockdown inhibited the Wnt/β-catenin axis in OC cells. Our findings indicate that silencing SHCBP1 repressed the growth, motility, and stemness of OC cells by inhibiting the Wnt/β-catenin axis. Conclusions: The abundance of SHCBP1 was enhanced in OC. Silencing SHCBP1 repressed the proliferation, migration, invasion, and stemness of OC cells by inhibiting the Wnt/β-catenin pathway. These results suggest that SHCBP1 may serve as a possible target in OC. [ABSTRACT FROM AUTHOR]

Background: Ovarian carcinoma is a malignant tumor with a poor prognosis. Due to the late onset of the first symptoms, most patients present with already advanced disease—at stage III or IV, which significantly reduces life expectancy. Despite advancements in surgical treatment, in particular, in chemotherapy, the mortality remains high, only slightly over 40% of female patients can expect a 5-year survival rate. Case: We report on an extremely rare case of a documented 45-year survival in serous ovarian cancer patient. The first diagnosis was confirmed in 1978, and she was treated surgically for histologically confirmed ovarian serous carcinoma. The first recurrence appeared in 2013 and was histologically confirmed in an open abdominal biopsy. The patient was successfully managed using carboplatin/paclitaxel chemotherapy and remained in remission. The second recurrence appeared in 2016 and was well managed with chemotherapy. In 2023, the histological examination of laparoscopic biopsy confirmed serous ovarian carcinoma relapse. The comparison of all biopsy samples proved the recurrence of the same tumor and excluded a secondary disease. Conclusions: This rare case of unusually long survival in serous ovarian cancer patient indicates that some patients may have a much better prognosis than typically observed. Advances in genetic determinations are needed to better understand the biology of this tumor to identify patients with the perspective of better survival. [ABSTRACT FROM AUTHOR]

Introduction Ovarian cancer is a leading cause of cancer mortality globally due to late-stage diagnosis and limited treatment options. PARP inhibitors have shown promise as effective treatments for recurrent and various stages of ovarian cancer. Aim of the Study This study reviews the efficacy and application of PARP inhibitors in ovarian cancer treatment over the past 15 years, focusing on literature from the PubMed database post-2009 and considering FDA and EMA guidelines. Review methods A literature review was conducted using the PubMed database, focusing on studies published after 2009. The review also incorporated recommendations from the FDA and the European Medicines Agency regarding the use of PARP inhibitors in ovarian cancer treatment. Results The findings highlight the substantial impact of PARP inhibitors on ovarian cancer treatment, improving PFS and overall outcomes. Olaparib, niraparib, and rucaparib have become integral to ovarian cancer management, offering effective options for patients with BRCA mutations or homologous recombination deficiencies. These inhibitors have been validated in multiple clinical trials, underscoring their robustness and effectiveness. Combination therapies, such as olaparib with bevacizumab, further enhance therapeutic outcomes, showcasing the potential for synergistic effects. Summary PARP inhibitors represent a significant advancement in ovarian cancer treatment, offering improved survival outcomes for patients with specific genetic profiles. Their integration into standard care protocols underscores their importance and efficacy, providing valuable therapeutic options in the fight against ovarian cancer. Key Words: PARP inhibitors, ovarian cancer, ovarian cancer treatment

Objective: To explore the effect of targeted psychological nursing, combined with physical activity, on self-management efficacy and compliance in patients with ovarian cancer undergoing chemotherapy, with a specific focus on athletes or physically active individuals. Methods: A total of 90 patients, including athletes and physically active individuals, diagnosed with ovarian cancer and receiving chemotherapy at our hospital from May 2019 to May 2021, were selected for this study. They were randomly divided into a control group and a study group, with 45 cases in each group. The control group received routine nursing care, while the study group was given targeted psychological nursing interventions in conjunction with structured physical activity programs. Selfmanagement efficacy, compliance, mental state, and quality of life were observed and compared between the two groups. Results: After 2 weeks and 3 months of intervention, the level of self-management efficacy in both groups was higher than before the intervention, with the study group showing significantly higher levels than the control group (P <0.05). The complete compliance rate in the study group was 75.55%, significantly higher than the control group's 44.44% (P<0.05). Post-intervention scores for the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Cancer-Related Fatigue (CRF) were lower in both groups compared to pre-intervention, with the study group showing significantly greater improvements than the control group (P <0.05). Furthermore, the life quality scores, particularly in physical status, emotional status, social and family interactions, and ovarian cancer-specific modules, were significantly higher in the study group compared to the control group (P <0.05). Conclusion: The implementation of targeted psychological nursing measures, coupled with structured physical activity, significantly improves self-management efficacy, treatment compliance, and quality of life in ovarian cancer patients undergoing chemotherapy, particularly among athletes and physically active individuals. These findings suggest positive clinical value in integrating psychological and physical activity interventions for this patient population. [ABSTRACT FROM AUTHOR]

Objective: Ovarian cancer is one of the most fatal gynaecological malignancies worldwide. In ovarian cancer patients, elevated interleukin-8 (IL-8) level was found in ovarian cyst fluid, ascites, serum, and tumour tissue. This study aimed to determine the relation between ascites' IL-8 level and progression-free survival (PFS) as well as overall survival (OS) in ovarian cancer patients. Material and Methods: This prospective cohort included ovarian cancer patients who underwent primary surgery at Sardjito General Hospital during the 2018-2021 period. Samples were taken from ascites fluid. Outcomes including PFS and OS were recorded at the end of this study. IL-8 level was measured with human cytokine magnetic 10-plex panel for luminex (commercial kit invitrogen). Results: The subjects of this study were 40 ovarian cancer patients. The median follow-up was 24 months. During follow-up, 22 participants (55%) were progression-free. Twenty participants (50%) survived at the end of the study. Patients with high IL-8 level significantly had 2.93 times more risk to develop disease progression (p=0.048) and shorter progression free survival time of 15.4 compared to 27.5 months (p log rank 0.02). High IL-8 also decreased OS time of 19.4 compared to 27.3 months but was not significant (p log rank 0.058). Older age significantly related to low overall survival (0% compared to 58.8%), p=0.003. Conclusion: IL-8 ascites increased the risk of disease progression significantly but did not lower overall survival significantly in ovarian cancer. Older age was found to be unbeneficial for overall survival in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Ovarian Cancer (OC) is a prevalent gynecological malignancy, underscoring the urgency to discover novel therapeutic approaches that enhance both clinical efficacy and safety. Taraxasterol (TA), an important component of dandelion, has been reported to exhibit inhibitory effects on the progression of various tumors. However, its specific role in OC is yet to be reported. In this present study, we observed that TA significantly inhibits the proliferation of OC cells, promotes apoptosis and reduces OC cell migration and angiogenesis. Mechanistically, TA targets the EPH receptor A2 (EphA2) receptor, thereby inhibiting OC progression. In conclusion, the ability of TA to suppress both cell proliferation and angiogenesis in OC through EphA2 targeting suggests its potential utility as a therapeutic agent for OC. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is the most lethal gynecological cancer in the United States. Among the different types of OC, serous ovarian cancer (SOC) stands out as the most prevalent. Transcriptomics techniques generate extensive gene expression data, yet only a few of these genes are relevant to clinical diagnosis. Methods: Methods for feature selection (FS) address the challenges of high dimensionality in extensive datasets. This study proposes a computational framework that applies FS techniques to identify genes highly associated with platinum-based chemotherapy response on SOC patients. Using SOC datasets from the Gene Expression Omnibus (GEO) database, LASSO and varSelRF FS methods were employed. Machine learning classification algorithms such as random forest (RF) and support vector machine (SVM) were also used to evaluate the performance of the models. Results: The proposed framework has identified biomarkers panels with 9 and 10 genes that are highly correlated with platinum–paclitaxel and platinum-only response in SOC patients, respectively. The predictive models have been trained using the identified gene signatures and accuracy of above 90% was achieved. Conclusions: In this study, we propose that applying multiple feature selection methods not only effectively reduces the number of identified biomarkers, enhancing their biological relevance, but also corroborates the efficacy of drug response prediction models in cancer treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinumresistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. Patients and Methods: We retrospectively divided patients with PRROC into two groups: bevacizumab plus chemotherapy (BEVCT group) and chemotherapy alone (CT group). Progressionfree survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. Results: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. Conclusion: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity. [ABSTRACT FROM AUTHOR]

The morbidity rate of ovarian cancer, a malignant tumour in gynaecological tumours, is rising, and it is considered to be the most lethal cancer. The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators. Surgical excision of the lesions, along with chemotherapy, is the conventional treatment for ovarian cancer; however, resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises. Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications, and this has emerged as a highly demanding issue. Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells. Ferroptosis is composed of the cystine/glutamate antiporter system (the system Xc-) and glutathione peroxidase 4 (GPX4). Solute carrier family 7 member 11 (SLC7A11) and solute carrier family 3 member 2 (SLC3A2) play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells, respectively. In cells, GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity. The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways, namely, the GPX4-glutathione (GSH) protective pathway, the ferroptosis suppressor protein 1 (FSP1)- coenzyme Q10 (CoQ10) protective pathway, and the guanosine 5'-triphosphate cyclohydrolase I (GCH1) protective pathway. In ovarian cancer cells, the postsynaptic density-95, discs-large, zona occludens 1 (PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2 (TAZ-ANGPTL4-NOX2) pathway can be regulated by Yes-associated protein (YAP)/TAZ, a downstream component of the Hippo pathway, leading to the modulation of ferroptosis. By targeting microRNA-587, lncRNA ADAMTS9 antisense RNA 1 (ADAMTS9-AS1) can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis. Although ferroptosis holds promise in overcoming the resistance mechanism, there remain obstacles in utilizing it as a cancer treatment, including the potential harm of drugs to healthy cells. Hence, additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies. [ABSTRACT FROM AUTHOR]

In ethnomedicine, Motandra guineensis (Thonn.) A.DC. (Apocynaceae) is used to massage abscessed gums and manage pain. This study aimed to evaluate the antiproliferative effect of leaves of M. guineensis against human ovarian (OVCAR3) and melanoma (MDA-MB-435) skin cancer cells. Crude ethanol extract and fractions of M. guineensis leaves were evaluated for antiproliferative effect on OVCAR3 and MDA-MB-435 cells using cell viability assay at 2 and 20 µg/ml. In addition, the inhibitory effect of extract and fractions on nitric oxide (NO) production with lipopolysaccharide (LPS) stimulation (Greiss assay) on murine macrophage cells (RAW 264.7) at 0.3125 - 10 µg/ml was evaluated. Cell viability was evaluated using murine macrophage cells while toxicity assessment was done on Vero cells. Antiproliferative activity profile (% cell death) of extract and fractions followed the order: butanol (30% and 23%) > aqueous (28% and 21%) > ethyl acetate (22% and 19%) > crude (22% and 0%) at 20 µg/ml in OVCAR3 and MDAMB-435 cell lines respectively. Percentage NO inhibitory activity showed hexane fraction with the highest activity and aqueous fraction with the least activity at 10 µg/ml. Extract and fractions were less toxic in Vero cells when compared to the standard drug, Tamoxifen. Toxicity assessment using murine macrophage cells showed no significant difference in cell viability when compared to standard. Results indicate antiproliferative potential, NO inhibitory potential and safety of crude ethanol leaf extract and fractions of M. guineensis. [ABSTRACT FROM AUTHOR]

Background: Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. Case Report: A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. Conclusion: Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses. [ABSTRACT FROM AUTHOR]

Cytokines have major role in regulating the biological processes such as cell growth and activation, chemotaxis, inflammation, immunity and tissue repair. The cytokines involvement in oncogenesis shows their role in signaling between inflammatory cells and invasive neoplastic tissue. This study assessed the association of epithelial and stromal immunostaining of panel of cytokines with overall survival and disease-free survival in malignant ovarian neoplasia women. The study included 28 ovarian cancer patients. The patients' age, staging, differentiation grade, histological type of tumors, treatment type and survivals (disease-free survival and overall survival) were evaluated. Immunohistochemical analysis was made to assess the epithelial and stromal immunostaining of interleukins (IL-2, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Cut-off values for the immunostaining cytokines were calculated through Receiver operating characteristic (ROC) curves. Kaplan-Meier curves were designed to evaluate the survival followed by Cox regression. ROC curves relating death to epithelial IL-8 staining and stromal TNF-alpha staining exhibited a cut-off value more than staining 1 for both cytokines. There was no statistical significance found in the evaluation of other cytokines and disease-free survival. Overall survival was shorter in patients with epithelial IL-8 staining 2/3 (p = 0.049). No statistical significance was found regarding TNF-alpha stromal. Multivariate analysis revealed that epithelial IL-8 staining 2/3 was an independent variable linked to lower overall survival ((Odds ratio (OR) = 18.515. 95% confidence interval (CI): (1.160--295.549)). Therefore, epithelial IL-8 immunostaining predicts overall survival of ovarian malignancy patients. This cytokine can be the target for discovering other types of management systems for epithelial ovarian cancer and borderline ovarian tumor. [ABSTRACT FROM AUTHOR]

Patients with ovarian clear-cell carcinoma have limited treatment choices, because they are resistant to the standard chemotherapeutic agents used in ovarian cancer. The phase II KEYNOTE-100 trial revealed that pembrolizumab monotherapy demonstrated a 15.8% objective response in patients with ovarian clear-cell carcinoma in the subgroup analysis, which is much higher than that of other histology subtypes of ovarian cancer. Immune checkpoint inhibitors may play a new role in the treatment of these malignancies. Genetic analyses revealed a significant proportion of ovarian clear-cell carcinoma carrying the AT-rich interaction domain 1A protein (ARID1A) mutation. The association between a higher frequency of ARID1A mutation and a higher response to immune checkpoint inhibitors in ovarian clear-cell carcinoma opens a new research topic. Herein, we report a patient with ovarian clear-cell carcinoma refractory to platinum-based chemotherapy, who was treated with a reduced dose of bevacizumab and pembrolizumab combination therapy and achieved a complete treatment response. [ABSTRACT FROM AUTHOR]

Background/Aim: We investigated factors affecting the long-term duration of bevacizumab-based maintenance therapy (BMT) and survival in patients with the first platinum-sensitive recurrence of ovarian cancer (PSR). Patients and Methods: We included patients with the first PSR in two tertiary centers from January 2015 till August 2021. All patients received six cycles of paclitaxel, carboplatin, and bevacizumab followed by BMT. We collected data including age at recurrence, histologic types, the status of BRCA mutation, platinum-free interval (PFI), extent of secondary cytoreductive surgery (SCS), presence of extra-abdominal disease, numbers of recurred lesions, cycles of BMT, progression-free survival (PFS), and cancer-specific survival (CSS). The median cycles of BMT were 13 (range=1-108). Results: A total 103 patients were included, who consisted of the short-term (<13 cycles; n=49; 47.6%) and long-term users of BMT (=13 cycles; n=54; 52.4%). High-grade serous carcinoma (HGSC), PFI >12 months, and optimal cytoreduction during SCS were favorable factors for the long-term duration of BMT. Moreover, PFI >12 months and the long-term duration of BMT were factors for improved PFS, and HGSC and PFI >12 months were related to improved CSS. Conclusion: PFI >12 months may be associated with the long-term duration of BMT and improved survival in patients with the first PSR. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do ovarian stromal cells (OSCs) influence the viability and growth of human preantral follicles in vitro ? SUMMARY ANSWER A feeder layer of OSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles. WHAT IS KNOWN ALREADY In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of OSCs. This co-culture notably enhances follicle survival and growth. STUDY DESIGN, SIZE, DURATION Pre-antral follicles were isolated from human frozen-thawed ovarian tissue biopsies and then encapsulated in 1% alginate scaffolds. These embedded preantral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth, and hormone production between the different groups. PARTICIPANTS/MATERIALS, SETTING, METHODS Primordial/intermediate and primary follicles were isolated from frozen-thawed ovarian tissue of cancer patients (n = 6). OSCs were then isolated from ovarian tissue of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on Days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA. MAIN RESULTS AND THE ROLE OF CHANCE A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean ± SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of OSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (P  < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (P  = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (P  < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; P  < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75< x <200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (P  = 0.006) in the alginate beads containing primordial and growing follicles cultured on the OSCs (54.1 ± 14.2 pg/ml) compared to those cultured without OSCs (29.9 ± 4.0 pg/ml). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION This study was conducted using a short-term culture, and none of the primordial/intermediate/primary follicles reached the antral stage. Further in vitro studies are required to investigate follicular developmental capacity, physiology, and steroidogenesis in alginate scaffolds with human OSCs. WIDER IMPLICATIONS OF THE FINDINGS Activating and growing human primordial/intermediate follicles to a secondary stage in in vitro short-term culture has posed a longstanding challenge. However, co-culturing with human OSCs has shown the potential to overcome this limitation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A. PhD scholarship awarded to H.V.), Fondation Louvain (awarded to C.A.A.; PhD scholarship awarded to S.M. as part of a legacy from Mr Frans Heyes, and PhD scholarship awarded to A.D. as part of a legacy from Mrs Ilse Schirmer), Foundation Against Cancer (grant 2018-042 awarded to A.C.), and the European Community Structural Funds and Lithuanian Research Council (Agreement registration No. D-19-0874). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Ovarian cancer has high rates of morbidity and mortality and a poor prognosis. A growing body of research suggests that CDC28 protein kinase regulatory subunit 1B (CKS1B) influences the progression of numerous carcinomas. However, the specific mechanism of CKS1B in ovarian cancer has yet to be elucidated. Here, this study aimed to investigate the involvement of CKS1B in the progression of ovarian cancer. Initially, we collected data from the Cancer Genome Atlas (TCGA) website and ovarian cancer tissues showed elevated CKS1B expression compared to healthy tissues, indicating a poorer prognosis. Immunohistochemistry (IHC) was used to detect CKS1B and programmed cell death 1-ligand 1 (PD-L1) levels and demonstrated that CKS1B is positively related to PD-L1 expression. Then, short-interfering (si)-CKS1B or sinegative control (si-NC) constructs were transfected into SKOV3 and OVCAR3 cells. Subsequently, cell viability was measured by cell counting kit-8 (CCK8) and colony formation assays, and the extent of apoptosis was assessed using flow cytometry. We found that CKS1B silencing inhibited cell growth and promoted cell apoptosis in ovarian cancer. In addition, the expression levels of CKS1B, B-cell lymphoma-2 (BCL2)- associated X (Bax), cleaved-caspase3 and PD-L1 were determined by western blotting. Furthermore, to investigate whether the inhibitory effects of si-CKS1B on ovarian cancer is related to the levels of PD-L1, we added PD-L1 to si-CKS1B transfected cells and found that cells that had been supplemented with PD-L1 exhibited an increased cell growth rate and a reduced apoptosis rate than si-CKS1B cells. Collectively, our data we demonstrated high levels of CKS1B in ovarian cancer cells, and found that the knockdown of CKS1B could alleviate the development of ovarian tumors by dysregulating the level of PD-L1 expression. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most fatal gynecologic malignancy. Low-grade type represents only 2-5% of all ovarian cancer pathological types. Its clinical characteristics, growth pattern, and response to treatment are distinct from high-grade serous ovarian carcinoma. In this study, we retrospectively evaluated the clinical features, prognostic factors, and survival of patients diagnosed with low-grade serous ovarian cancer from a tertiary cancer centre. This is a retrospective study where all patients diagnosed with lowgrade serous ovarian cancer (LGSOC) who presented to a tertiary cancer centre from July 2015 to August 2021 were included. Forty-two patients with low-grade ovarian serous carcinoma were enrolled. The mean age of the patients was 50.17 ± 10.91 years, while the mean Body Mass Index (BMI) was 32.96 ± 6.02 kg/m2. Primary optimal debulking was performed in 18 patients, while interval cytoreduction was done in 17 patients. Suboptimal debulking was performed in 5 patients. Neoadjuvant chemotherapy was administered in 19 patients (45.2%). The median overall survival of LGSOC patients was 95.58 (73.37-117.79) months while the median Progression free survival (PFS) was 56.54 (38.15-74.94) months. Primary cytoreductive surgery is still the cornerstone of the management of LGSOC patients. Neoadjuvant chemotherapy could be a predictor of worse progression-free survival in LGSOC patients presented with advanced disease stage. [ABSTRACT FROM AUTHOR]

Surgical site infection (SSI) is associated with substantial morbidity. However, the incidence and clinical significance of SSIs after cytoreductive surgery in Korean females with epithelial ovarian, fallopian tube and peritoneal cancer (EOFPC) are unknown. We aimed to assess the incidence and consequences of SSI within 30 days after cytoreductive surgery in patients with EOFPC. After estimating the effect size, SSIs were retrospectively investigated in 149 patients between 2011 and 2020. Survival and multivariate analyses were performed using Kaplan-Meier estimates and the Cox regression method that included the interaction terms, respectively. Clinical factors for patients with or without SSI were compared using the Mann-Whitney U test and Fisher's exact test. The overall rate of SSI was 9.4% (14 of 149 patients), consisting of five superficial, three deep and six organ/space SSIs. No clinical significance of SSI was observed when analyzing the 149 cases. Among the 91 patients with FIGO stage III-IV serous type carcinomas, eight experienced SSI, and their clinical factors were compared with those of the 83 patients without SSI. A univariate analysis showed that patient age, neoadjuvant chemotherapy, suboptimal debulking status, FIGO stage, chemoresistance, a longer interval from surgery to initiation of chemotherapy (ISIC), and SSI occurrence were significantly associated with overall survival. The multivariate analysis showed that higher FIGO stage (HR 21.138; 95% CI 2.796-159.819; p = 0.003) and SSI occurrence (HR 21.999; 95% CI 2.616-184.986; p = 0.004) were independent predictors for poor overall survival. The SSI group had a significantly greater body mass index (p = 0.006) and a longer ISIC (23 ± 9.1 vs. 40.0 ± 25.7 days; p = 0.006) compared with the non-SSI group. In conclusion, SSI after cytoreductive surgery in patients with FIGO stage III-IV serous type carcinoma significantly worsened patient prognosis and delayed initiation of adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

MRI image evaluation of cystic ovarian neoplasms was done manually and is generally carried out by Radiologists using a manual technique called linear measurement. This technique has some weaknesses, including being considered a rough calculation estimate because measurements are made on only one largest slice and are vulnerable to subjectivity factors. This research applied a digital image processing program based on Matlab using a segmentation process and active contour Laplacian of Gaussian (LoG) in the measurement and calculation of the volume of cystic ovarian neoplasms. Analyze the differences in measurement results and find out which technique is better in the calculation of cystic ovarian neoplasm volume between techniques of linear measurement and techniques of active contour Laplacian of Gaussian (LoG). The research was done with 32 images of abdominal-pelvic MRI images with clinical cystic ovarian neoplasms, and measurements and calculations of the volume of cystic ovarian neoplasms were carried out using the technique linear measurement and active contour Laplacian of Gaussian (LoG). Measurement and calculation are done by Radiologists as an observer with data analysis using statistical processing. Analysis of MRI images of abdominal-pelvic MRI images with clinical cystic ovarian neoplasms using linear measurement and active contour Laplacian of Gaussian (LoG) techniques showed a difference with a p-value of 0.004 (p<0.05). The results of measurements using the active contour laplacian of the Gaussian technique are better than the linear measurement, as indicated by the higher mean rank of the active contour laplacian of Gaussian, which was 17.50 (higher than the linear measurement value of 13.50). [ABSTRACT FROM AUTHOR]

Malignant pericardial effusion is an uncommon metastatic manifestation of ovarian carcinoma. Few cases of ovarian serous carcinoma have been previously reported. Ovarian clear cell carcinoma is the second most common histologic subtype in East Asian countries and is a relatively rare in Western countries. Here, we report the case of cardiac tamponade secondary to Ovarian clear cell carcinoma. A 46-year-old woman with recurrent Ovarian clear cell carcinoma presented with worsening cough, palpitations, and shortness of breath during chemotherapy. Chest radiography and computed tomography confirmed a pleural effusion with cardiac tamponade. The patient underwent pericardial fenestration and drainage for cardiac tamponade. Pericardial fluid cytology showed malignant cells forming papillary and ball-like clusters with irregular stacking. The cells had a mirror ball-like appearance and collagenous stroma, in which a homogenous hyaline core was observed in the center of most tumor cell clusters. Based on these findings, a diagnosis of Ovarian clear cell carcinoma metastasis was made. She received palliative care and died 5 months after the operation without recurrent cardiac tamponade. This case suggests that cytological findings from pericardial effusion are useful in diagnosing Ovarian clear cell carcinoma metastasis. [ABSTRACT FROM AUTHOR]

Yu Been Shin,1,&ast; Ju-Yeon Choi,2,&ast; Dae Hwan Shin,1 Jeong-Won Lee2,3 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea&ast;These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email dshin@chungbuk.ac.kr Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea, Tel +82-2-3410-1382, Fax +82-2-3410-0630, Email garden.lee@samsung.comPurpose: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied.Methods: Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy.Results: Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of − 0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation.Conclusion: There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.Keywords: ovarian cancer treatment, combination therapy, drug delivery, nanoformulation

Ovarian cancer is a leading cause of death in females with gynecologic cancers. Pyroptosis is a relatively new discovered programmed cell death that is believed to be associated with inflammation. However, studies on pyroptosis-related lncRNAs in ovarian cancer are limited. In this study, we identified 29 pyroptosis-related genes and screened out 72 pyroptosis-related lncRNAs. Furthermore, the 72 lncRNAs were eliminated to 2 survival-related lncRNAs using Cox regression and Lasso regression to build an ovarian cancer prognostic prediction signature and were further validated on the test set. We adopted a riskscore from the two-gene signature, and the survival in low-risk group was higher than the high-risk group. Functional enrichment analysis indicated that the differentially expressed genes (DEGs) between two risk groups were associated with tumor immunity. This study implies that pyroptosis-related genes are closely related to tumor immunity and could be potential therapeutic factors for ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

We aimed to investigate the mechanism of action of Zhimu in the treatment of ovarian cancer (OC) using network pharmacology. OC targets were screened using the DisGeNET and Online Mendelian Inheritance in Man databases. Common OC and Zhimu targets were identified using the Traditional Chinese Medicine System Pharmacology, UniProt databases, and Venny 2.1.0. The protein-protein interaction (PPI) network in the Search Tool for the Retrieval of Interacting Genes/Proteins database was created using Zhimu/OC targets and a Zhimu active ingredient-target-pathway network in the Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the Metascape database. And overall, 15 active ingredients in addition to 93 related targets were identified. The PPI network had 52 targets that overlapped with it, with the 10 most relevant targets being the tumour protein p53, tumour necrosis factor, serine/threonine kinase 1, vascular endothelial growth factor A, caspase-3, prostaglandin G/H synthase-2, hypoxia-inducible factor-1 alpha, interleukin-1 beta, heat-shock protein 90-alpha, and progesterone receptor. According to GO and KEGG analyses, Zhimu and OC had the nuclear factor NF-kappaB signalling pathway, oxidative stress, and the advanced glycation end product (AGE)/the receptor for the advanced glycation end product (RAGE) signalling pathway as common targets. This study highlighted the active ingredients in Zhimu and identified potential molecular therapeutic mechanisms for the treatment of OC. It also provided suggestions and directions for future research into molecular mechanisms. [ABSTRACT FROM AUTHOR]

Context • Paclitaxel (PTX) resistance is often associated with poor outcomes for patients with ovarian cancer (OC), but its mechanism is unknown. Clinicians are increasingly using immunotherapy in the management of OC, and the ability to assess tumor-immune interactions and identify effective, predictive, prognostic molecular biomarkers for OC is an urgent need. Objective • The study intended to explore the potential tumorigenesis mechanisms to identify promising biomarkers and improve survival in OC patients. Design • The research team performed a genetic analysis. Setting • The study took place at First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. Outcome Measures • The research team: (1) obtained GSE66957 and GSE81778 gene expression profiles from the Gene Expression Omnibus (GEO) database and identified 468 differentially expressed genes (DEGs); (2) conducted functional enrichment analysis and constructed a protein-to-protein interaction (PPI) network; (3) identified the OC survival-related genes using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) webserver and compared those genes with upregulated DEGs to identify the core genes; (4) used GEPIA2 and the Kaplan-Meier plotter to explore the expression profiles and the prognostic values of the core genes in OC; (5) used the LinkOmics, Oncomine, and GEPIA2 web servers to perform co-expression analysis and explore functional networks correlated with keratin 7 (KRT7); (6) performed correlation analyses between KRT7, the six main types of tumor-infiltrating lymphocytes (TILs), and immune signatures, using the TIMER tool; and (7) subsequently detected the KRT7 expression in the cell lines IOSE80, A2780, A2780/PTX, ho8910, skov3, and ovcar3 using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) technology. Results • High expression levels of KRT7 were significantly correlated with progression-free survival (PFS) and poor overall survival (OS) for OC patients, with logrank P=.0074 and logrank P=.014, respectively. The expression levels of KRT7 were also significantly correlated with the infiltrated neutrophil levels (r = 0.169, P = .0077). The study identified neutrophils as potential predictors of survival in OC. Moreover, the expression levels of KRT7 in OC were positively correlated with 51 (31.68%) of the 161 immune gene markers. The RT-qPCR analyses revealed a high expression of KRT7 in the paclitaxel)resistant OC cell line. Conclusions • KRT7 is correlated with immune infiltration and paclitaxel resistance in OC patients. Therefore, clinicians could use KRT7 as a prognostic marker and a target in the development of new drugs. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) and cervical cancer (CC) are common malignancies in women in clinical practice. More uncommon non-ovarian malignancies, such as vulval cancer (VC), are also becoming more prevalent in women of all ages. Currently, there are few comprehensive reviews on the management of these conditions, despite the recent advances in the use of immunotherapy in the management of other forms of cancer. The treatment modalities for EC, CC and VC vary; however, platinum-based chemotherapy, surgical resection and radiotherapy are the main forms of treatment. In more advanced or recurrent disease, there is a limited number of efficacious treatments, with many clinicians relying on adjuvant chemotherapy despite the increased rationale for the use of immunotherapy. With the development of the novel adoptive T-cell therapy, intra-tumoural oncolytic viral therapy and cancer vaccines, the landscape of gynaecological cancer management is changing, and it is likely that treatment efficacy and outcomes will improve dramatically. This review aims to summarise the current management of endometrial, cervical and vulval cancer and to evaluate the novel therapies under development, as well as the future of the management of non-ovarian gynaecological malignancies. [ABSTRACT FROM AUTHOR]

Background: Whether or not patients with stage I epithelial ovarian cancer (EOC) benefit from postoperative chemotherapy in the Asian population remains unclear. This retrospective cohort study was aimed at investigating the use of adjuvant chemotherapy in clinical practice to treat patients with early-stage EOC considering clinical factors. Materials and Methods: A total of 414 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IA--IC and grade 1 EOC were enrolled from the Taiwan Cancer Registry. We used multivariable Cox proportional-hazards models to control for clinical factors. The overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan--Meier method. Results: DFS did not improve significantly for patients with FIGO stage IA/IB EOC receiving adjuvant chemotherapy, with a 10-year DFS rate of 98% and 88% for those with and without adjuvant chemotherapy, respectively (hazard ratio [HR] = 0.41, 95% confidence interval [CI]: 0.05--3.36). OS did not improve significantly for patients with FIGO stage IA/IB EOC with adjuvant chemotherapy (HR = 0.86, 95% CI: 0.18--4.22) or stage IC (HR = 0.50, 95% CI: 0.10--2.45). OS did not differ significantly for patients with optimal (10-year OS: 92% with chemotherapy and 86% without chemotherapy in the log-rank test, P = 0.629) or nonoptimal staging (10-year OS: 73% with chemotherapy and 90% without chemotherapy in the log-rank test, P = 0.959). Conclusion: Adjuvant chemotherapy did not improve the prognosis of patients with low to intermediate-risk EOC and optimal/nonoptimal surgery. This result should be considered in clinical practice. [ABSTRACT FROM AUTHOR]

Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer. Knockdown or pharmaceutical inhibition of PRMT5 is sufficient to decrease glycolysis flux, attenuate tumor growth, and enhance the antitumor effect of Taxol. Mechanistically, we find that PRMT5 symmetrically dimethylates alpha‐enolase (ENO1) at arginine 9 to promotes active ENO1 dimer formation, which increases glycolysis flux and accelerates tumor growth. Moreover, PRMT5 signals high glucose to increase the methylation modification of ENO1. Together, our data reveal a novel role of PRMT5 in promoting ovarian cancer growth by controlling glycolysis flux mediated by methylating ENO1, and highlights that PRMT5 may represent a promising therapeutic target for treating ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the symptoms of women with epithelial ovarian cancer (EOC) during their last admission before death and analyze invasive palliative management administered in relation to symptom control and survival. Materials & Methods: A retrospective review of Israeli patients with EOC, primary peritoneal cancer (PPC) and tubal cancer, admitted to our department prior to death between 2008–2018. Basic palliative treatment was defined as administration of IV fluids, analgesics, oxygen, antiemetics, antibiotics and/or blood transfusions. Procedures regarded as invasive included: peritoneal or pleural fluid drainage; placement of an indwelling catheter, administration of total parenteral nutrition (TPN), chemotherapy and ventilation. Results: 82 patients were included. Most suffered from weakness and fatigue, gastrointestinal complaints, pain and shortness of breath. 34 patients (41.5%) required only basic palliative treatment to alleviate their symptoms; however, in 48 patients (58.5%) invasive interventions were needed. Patients treated with invasive procedures were younger at death by almost 9 years (mean age of 65.73 ± 9.5 vs. 74.78 ± 9.8; p = 0.001). There were significantly more women with platinum sensitive disease in the invasive interventions group compared to the basic palliative care (60.42% vs. 32.35%; p = 0.012). No survival difference was found between the groups from diagnosis to death, relapse to death, last chemotherapy to death and last admission to death. Conclusions: EOC patients suffer from high disease burden and multiple symptoms before death. We found that physicians tend to use more invasive care in dying younger patients. However, this aggressive treatment does not prolong survival. Futile treatments influencing quality of life should be avoided. [ABSTRACT FROM AUTHOR]

Peritoneal mesothelioma is a rare neoplasm that is associated with multiple diagnostic and therapeutic challenges. Therapeutic guidelines are scarce and based on extrapolative data. Histopathological diagnosis is difficult as neither the morphological finding nor the immunohistochemical stains are specific. The mainstay treatment for resectable disease is cytoreductive surgery with intraperitoneal chemotherapy being a valuable addition. Treatment of non-resectable cases includes platinum-based chemotherapy, immune checkpoint inhibitors, and bevacizumab. We present a case of a 49-year-old woman suffering from inoperable peritoneal mesothelioma, which was initially diagnosed as ovarian cancer and treated accordingly. [ABSTRACT FROM AUTHOR]

Purpose: Ovarian cancer patients require monitoring for relapse post-treatment, and alternative follow-up pathways are increasing, which require in-depth exploration to ensure acceptability and inform implementation. This study aimed to explore women and specialist nurses' experiences of participating in a feasibility study of an electronic patient-reported outcome (ePRO) follow-up pathway after ovarian cancer treatment. Methods: The feasibility study incorporated an ePRO questionnaire, blood test and telephone consultation with a specialist nurse, instead of face-to-face hospital visits. All women and the nurses involved were invited to take part in nested semi-structured interviews. Interviews were recorded and transcripts analysed using framework analysis. Results: Twenty interviews were conducted (16 out of 24 women who took part in the feasibility study and all 4 nurses). Four themes were identified: (1) readiness and motivators, (2) practicalities and logistics, (3) personal impact and (4) future role. An overarching theme highlighted how women strived to seek reassurance and gain confidence. Most women and nurses were positive about the ePRO pathway and would happily continue using it. Conclusion: This work provides invaluable insight into the experiences of women on remote ePRO follow-up post-treatment. Important logistic and implementation issues were identified, which should inform future large-scale work to introduce and evaluate remote ePRO methods in cancer follow-up. This work highlights the key factors influencing women's readiness and acceptability of an ePRO pathway, and how services should be carefully designed to ensure patients feel reassured and confident post-treatment. Furthermore, it highlights that flexibility and patient preference should be considered in remote service delivery. Trial registration: ClinicalTrials.gov ID: NCT02847715 (first registered 19 May 2016). [ABSTRACT FROM AUTHOR]

Ovarian cancer (OV) is usually diagnosed in its advanced stages (stages III or IV), minimally invasive surgery (MIS) is increasingly being used to treat advanced OV due to several advantages over laparotomy. MIS represents a novel but controversial treatment approach for interval debulking surgery (IDS). The objective of this review was to clarify the feasibility and safety of MIS for IDS. WanFang database, Chinese National Knowledge Infrastructure (CNKI) databases, Embase, PubMed, Cochrane, Clinicaltrials.gov and Web of Science were searched up to June 2022, Clinical studies based on humans, including randomized controlled trials, quasi-RCTs, nonrandomized trials, case-control studies, cohort studies and retrospective observational studies, were included without time restriction. 14 original articles published between 2015 and 2022 were included. In total, there were 13,788 patients enrolled, 2318 (16.8%) were treated with MIS. The pooled rate of laparotomy-conversion was 17.9% (112/711), the pooled rate of optimal cytoreduction was 84.0% (628/748) during MIS group compared with 77.3% (2204/2850) during laparotomy (LAP) group (p < 0.0001), and the pooled rate of perioperative complication was 8.85% (79/893) during MIS versus 4.6% (211/4586) during LAP group (p < 0.0001). We found no significant difference in mean progression-free survival (PFS) and mean overall survival (OS) between two groups. Based on the available retrospective studies, minimally invasive debulking surgery after NACT seemed to have similar perioperative, oncological and prognostic outcomes with laparotomy debulking surgery. MIS seemed to be feasible and safe in carefully selected patients who had good response to NACT, lower preoperative levels of CA12-5 and lower tumor burden. However, existed clinical evidence should be viewed with caution and objectivity. MIS for IDS should be cautiously suggested until the observed results are confirmed in the LANCE trial and other larger prospective trials. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to assess the usefulness of determining HE4 and CA125 in ovarian cancer patients, to indicate which of the measurements may be optimal in the prognosis, depending on the treatment scheme. Material and methods: The concentrations of CA125 and HE4 were performed in 70 patients with advanced ovarian cancer during I-line therapy and after treatment. The subjects were divided based on the treatment scheme: group I - primary surgery and adjuvant chemotherapy, II-neoadjuvant therapy, and surgery. Results: Multivariate analysis showed that HE4 levels six months after treatment was significantly higher in patients with disease progression. ROC analysis in the group of patients treated with neoadjuvant therapy showed that the cut-off values indicating relapse for HE4 and CA125 after six months of follow up, were > 90.4 pmol/L, > 25.6 IU/mL, respectively. In the group of patients not treated with neoadjuvant therapy, the cut-off points differentiating patients with progression were: HE4 > 79.1 pmol/L, CA125 > 30.7 IU/mL. We demonstrated significantly higher HE4 and CA125 at both 6- and 12-months follow-up in patients treated with neoadjuvant therapy. In both groups of patients, the cut-off points were lower than those proposed by the manufacturer of the kits. Conclusions: Measurement of HE4 six months after treatment may be useful in identifying patients at high risk of progression, especially when CA125 levels may be non-specifically elevated. The cut-off values indicating relapse for HE4 and CA125 after six months of follow up may be lower than the normal range. [ABSTRACT FROM AUTHOR]

Ovarian low-grade serous carcinoma (LGSC) is usually a slow growing tumor with a relatively good prognosis. However, LGSC that have relapsed are highly resistant to chemotherapy, and there is currently no established treatment for them in contrast to high-grade serous carcinoma (HGSC). Here, we first review the literature on this topic and then describe a case of LGSC that relapsed and responded to Gemcitabine and Bevacizumab. The patient was a 37-year-old nulliparous woman who had undergone three cycles of topotecan after initial surgery at age 28.5 years as well as three months later during a disease-free interval. Intraperitoneal dissemination was observed and laparoscopic biopsy was performed. Histopathological examination revealed LGSC, and genetic testing revealed mutations in the neurofibromatosis type 1 (NF1) and TP53 genes. The mass of the disseminated lesion subsequently increased overall, and subileus was observed. The patient was treated, but the operation was incomplete. Postoperatively, Gemcitabine and Bevacizumab therapy was started. After six cycles, tumor markers became negative and Positron Emission Tomography-CT (PET-CT) showed decreased tumor activity. There were 20 cycles without any symptoms. LGSC is often resistant to anticancer drugs, but Gemcitabine and Bevacizumab therapy was able to suppress the lesions and symptoms in this case. With these findings, future genomic testing may assist in the treatment strategy for cases of LGSC recurrence, which are considered to be less likely to respond to anticancer drugs. Comprehensive genetic analysis will hopefully lead to the molecular mechanism of carcinogenesis for more effective and targeted therapies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to review the characteristics and survival of patients with Advanced Epithelial Ovarian Cancer undergoing neoadjuvant chemotherapy (NACT) and the impact of timing of surgery and post-operative adjuvant chemotherapy (CCT). Methods: Retrospective multicentre study, of patients with an initial diagnosis of advanced high-grade epithelial ovarian carcinoma, considered inoperable at diagnosis and treated with NACT. Results: Eighty-six patients were analyzed. Fifty-seven underwent surgery, with significantly higher median overall survival (mOS) versus those who were never operated. The percentage of complete surgery (R0) was 74%, with a median progression-free survival (mPFS) of 45 months and mOS of 67 months versus mPFS of 27 months and mOS of 28 months in patients with residual disease. Of the operated patients, 21 underwent 3-4 cycles of NACT and 36 5-6 cycles of NACT, with a mOS of 64 months and 38 months respectively. Patients with almost complete/complete NACT response had significantly improved PFS and OS compared with patients with partial/minimal/absent response. Twenty-two patients underwent 2-3 cycles CCT with no significant differences in terms of PFS or OS. COX regression showed that both the increase in time between NACT and surgery and the chemotherapy response score are related to the risk of death. Conclusions: Complete surgery and Chemotherapy Response Score (CRS) were the most important prognostic factors for survival in this population. The use of CCT showed no advantage in survival outcomes. Prospective studies are needed to evaluate new therapeutic strategies for patients with inoperable ovarian cancer at diagnosis. [ABSTRACT FROM AUTHOR]

Background: Treatment of recurrent ovarian cancer may consist of salvage chemotherapy or secondary cytoreductive surgery. Retrospective studies suggest that radical secondary cytoreduction resulting in no macroscopic disease (R0) after completion of surgery benefits patients and prolongs survival. The role of robotic-assisted secondary cytoreductive surgery (RASCS) is in its infancy. The aim of this manuscript is to review the literature regarding the role, the indication, and the techniques of RASCS and to summarize the published perioperative, postoperative, and oncologic outcomes of RASCS. Methods: A comprehensive systemic review was conducted in the PubMed, MEDLINE, EMBASE, and Google Scholar databases from 1 January 1980 through 31 December 2021. Keywords searched were "ovarian cancer", "recurrence", "robotic-assisted secondary debulking/cytoreductive surgery", "morbidity and mortality of secondary cytoreductive surgery", "indications for secondary cytoreductive", and combinations of these terms. Studies selected and analyzed included randomized controlled trials (RCTs) as well as prospective and retrospective anlayses and case series. RASCS procedures and techniques are described. Results: Several retrospectives, meta-analyses and prospective randomized trials suggest that optimal secondary cytoreductive surgery is associated with extended progression-free and overall survival. Preoperative selection criteria, such as Memorial Sloan Kettering (MSK) criteria and AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) scores demonstrate that clinical-pathological factors can predict optimal secondary cytoreductive surgery and correlate with improved progression-free survival and overall survival. The surgical procedures that are required in secondary cytoreductive surgery can be complex. Limited retrospective studies have demonstrated that secondary cytoreductive surgery utilizing a robotic surgical platform can achieve the same rate of optimal cytoreductive surgery as open laparotomy with decreased morbidity. The effect of RASCS on progression-free and overall survival has not been established. Conclusions: Early literature reports indicate that RASCS, in selected patients, can be applied for surgical treatment of recurrent ovarian cancer without compromising morbidity; long-term studies are warranted to determine the effect on progression-free and overall survival. [ABSTRACT FROM AUTHOR]

The main reason for treatment failure in ovarian cancer is chemoresistance and the presence of metastasis. Ascites, which allows the physical movement of cancer cells, the lymphovascular pathway, and several molecular factors and signalling axes, are involved in metastasis. Ascites, with the involvement of cytokines and chemokines, MAPK/STAT1 and NOTCH as well as CXCL12/CXCR4 signaling pathways and circulating anoikis induces cancer dissemination, in particular to the peritoneum and omentum. The spread of lymphatic and bloodstream cancer cells is a multi-stage process. Tumour infiltration of the stroma and lymphovascular space (LVSI) produces biologically active cancer-associated fibroblasts and macrophages (CAFs, TAMs) that secrete numerous cytokines, chemokines and growth factors, inhibit NK function, induce epithelial-mesenchymal transition (EMT), resulting in an increase of the metastatic potential of cancer cells and the formation of cancer stem cells (CSCs). Overexpression of some genes, and microRNAs, in LVSI-(LMGS) associated with metastasis has been identified. The role of extracellular vesicles (EVs) transporting metastasis-associated factors has been described as has the role of cancer stem cells (CSCs) in chemotherapy resistance and metastasis. Sirtuins, enzymes involved in metastasis formation, have also been detected. Certain types of microRNAs (miR-509-3p, microRNA-506-3p) and melatonin have been shown to inhibit metastasis. [ABSTRACT FROM AUTHOR]

Background/Aim: Some studies have shown that ovarian cancer patients admitted after referral to the emergency department had a worse prognosis than those referred through non-emergency pathways. We believe that our study is the first in the UK to explore this difference and aimed to compare the 1-year, 3-year, and 5-year overall survival rates of ovarian cancer patients referred non-urgently from the general practitioner (GP) vs. patients referred urgently to the emergency department (ED). Patients and Methods: This was a retrospective cohort study conducted at the University Hospitals of Leicester (UHL) from 1st January 2015 to 31st December 2019 involving 298 ovarian cancer patients: 197 referred nonurgently from the GP and 101 patients referred to the ED. Results: There was no significant difference in the 1-year, 3-year, and 5-year overall survival in ovarian cancer patients referred from the GP compared to patients referred to the ED, 84.8%, 62.2%, and 48.4% versus 80.2%, 64.8%, and 43.5%, respectively (p=0.732). Conclusion: The mode of referral for ovarian cancer patients may not affect their prognosis. Prompt referral to the gynaecological oncology multidisciplinary team, a good acute oncology service, early imaging and image-guided diagnostic pathways, timely appointment, and timely initiation of treatment in our centre may have minimized the difference in outcome in the two groups. [ABSTRACT FROM AUTHOR]

Surgical procedures of the retroperitoneum are often performed in gynecologic oncology surgery clinics. The most complex among them is paraaortic lymphadenectomy. It is generally performed in cases of bulky lymph nodes in ovarian carcinomas and sarcomas to achieve optimal cytoreduction. In the early stages of ovarian cancer, type II non-endometrioid endometrial cancer, and in advanced stages of cervical cancer, paraaortic lymphadenectomy is an integral part of staging. Moreover, the retroperitoneum is approached in cases of retroperitoneal gynecologic sarcomas. The largest vessels of the human body – the inferior vena cava and the abdominal aorta are localized in the retroperitoneum. Therefore, iatrogenic vessel injury during oncogynecological surgery is more likely to affect the inferior vena cava. Anatomical variations of the vein additionally increase the risk of vascular lesions. Therefore, surgeons should be aware of possible anatomical variations. The present article aimed to highlight the heterogeneity of anatomical variations of the inferior vena cava related to gynecologic oncology surgery. Embryogenesis of the vein and its variations are also discussed. Additionally, some anomalies of the ureter, associated with the embryogenesis of the inferior vena cava, are mentioned. [ABSTRACT FROM AUTHOR]

Background: Being highly malignant, ovarian carcinoma mostly presents at an advanced stage at the time of diagnosis. The appendix could be a potential site for metastatic involvement by ovarian malignancy, however, this is a rare event. Though, its presence can upgrade the tumor to stage III. Case Presentation: We report a post-menopausal patient with abdominal mass and distension. Computed tomography scan showed bilateral adnexal lesions, an enlarged enhancing appendix, right hydroureteronephrosis, and ascites. On histopathological correlation, the adnexal lesions turned out to be moderate to poorly differentiated papillary adenocarcinoma with omental and appendiceal involvement by the pathologic process. The patient was then referred to the Oncology department. Conclusion: Clinical assessment of appendix or routine appendectomy as part of late-stage ovarian carcinoma management in older patients with omental involvement can lower the risk of appendiceal involvement with subsequent downstaging of the tumor. [ABSTRACT FROM AUTHOR]

Background/Aim: The COVID-19 pandemic has significantly influenced the management of oncogynecologic patients in regard to time of diagnosis, to delay of treatment, therapeutic strategy and postoperative complications. The aim of the study was to investigate the impact of preoperative SARS-Cov2 infection on the postoperative outcome after debulking surgery for ovarian cancer. Patients and Methods: Between June 2021 and September 2021, 12 patients with antecedents of COVID-19 infection and ovarian cancer were submitted to surgery at "Dr. I. Cantacuzino" Hospital, Bucharest, Romania. Their outcomes were compared to those reported in a similar group of patients submitted to surgery during the same period in the absence of COVID-19 infection. Results: Although preoperative data showed no statistically significant differences between the two groups, intraoperative length and estimated blood loss were higher in the COVID-19 group and so were the postoperative complications, the most commonly encountered ones being reported by wound infection, postoperative hemoperitoneum and pneumonia. However, the differences did not reach statistical significance. Conclusion: Preoperative COVID-19 infection seems to slightly increase the risk of postoperative complications after debulking surgery for ovarian cancer. [ABSTRACT FROM AUTHOR]

Ovarian Cancer (OC) is among the most prevalent cancers in females. OC is one of the deadliest and worst prognosis diseases. Currently, there are no approved OC screening tests or early detection methods. Hence, new screening, prevention, and early detection strategies are still highly demanded. Plant compounds have recently become increasingly important in developing new, effective, and affordable anti-cancer drugs. To investigate the protein-ligand interaction, molecular docking was used with the Molecular Operating Environment (MOE) tool to find the best inhibitor for the target proteins. Compound spatial affinity for the active sites of the NY-ESO-1, RUNX3, and UBE2Q1 proteins was calculated using molecular docking. ADMET analysis was used to determine the drug-likeness of the selected compounds, while MD simulation and MMGBSA/MMPBSA experiments were used to further understand the binding behaviors. Preclinical tests can help confirm the validity of our in silico studies and determine whether the compound can be used as an anticancer drug to treat OC. [ABSTRACT FROM AUTHOR]

Background: Adnexal masses are a common problem seen in women. The aim of this study was to determine the appropriate cut-off for symptom-based score to predict ovarian malignancy in women with adnexal mass and to evaluate it in combination with CA125. Methods: This was a prospective study involving 341 women with adnexal mass who underwent surgery. A symptom-based scoring system was administered to the women, preoperatively, and CA125 levels were documented. Receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cut-off for the symptom-based scoring. Results for this symptom-based scoring and CA125 were correlated with surgical pathological findings. Results: Out of the 341 women with adnexal mass, 112 were diagnosed to have ovarian malignancy. The mean age of women was 43.6±13.8 years. Using ROC analysis, symptom score ≥9 was determined to be the appropriate cut-off. The area under curve (AUC) at this cut-off score was found to be 0.87 (95% CI 0.83–0.91). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at this cut-off was found to be 84.8%, 88.6%,78.5%, and 92.3%, respectively. Combining CA125 and symptom score resulted in higher sensitivity (96.4%) and NPV (97.4%) with specificity and PPV of 65.5% and 57.8%, respectively. Conclusion: Symptom score in combination with CA125 has good ability to predict ovarian malignancy in women with adnexal masses. [ABSTRACT FROM AUTHOR]