Treatment Of Ovarian Cancer Research Articles

EHMT1/2 inhibition promotes regression of therapy-resistant ovarian cancer tumors in a CD8 T cell-dependent manner.

Poly ADP-ribose polymerase inhibitors (PARPi) are first-line maintenance therapy for ovarian cancer and an alternative therapy for several other cancer types. However, PARPi-resistance is rising and there is currently an unmet need to combat PARPi-resistant tumors. Here, we created an immunocompetent, PARPi-resistant mouse model to test the efficacy of combinatory PARPi and euchromatic histone methyltransferase 1/2 inhibitor (EHMTi) in the treatment of PARPi-resistant ovarian cancer. We discovered that inhibition of EHMT1/2 resensitizes cells to PARPi. Markedly, we show that single EHMTi and combinatory EHMTi/PARPi significantly reduced PARPi-resistant tumor burden and that this reduction is partially dependent on CD8 T cells. Altogether, our results show a low-toxicity drug that effectively treats PARPi-resistant ovarian cancer in an immune-dependent manner, supporting its entry into clinical development and potential incorporation of immunotherapy. Implications: Targeting the epigenome of therapy-resistant ovarian cancer induces an anti-tumor response mediated in part through an anti-tumor immune response.

MicroRNA‑mediated approaches in ovarian cancer therapy: A comprehensive systematic review.

Ovarian cancer (OC) poses a significant health risk to women worldwide, with late diagnoses and chemotherapy resistance leading to high mortality rates. Despite several histological subtypes, the primary challenge remains the subtle nature of its symptoms, resulting in advanced-stage diagnosis and reduced treatment success rates. With platinum-based therapies showing relative efficacy but limited survival enhancements, the emergence of chemotherapy resistance during recurrence remains a critical obstacle. Precision medicine development has aimed to address these challenges in the context of the molecular diversity of OC. The present review explored the landscape of microRNA (miRNA)-mediated approaches in OC treatment. miRNAs have emerged as regulators of gene expression, serving as both oncogenes and tumor suppressors in OC. Dysregulated miRNAs are associated with disease progression and chemotherapy resistance, underscoring their significance in diagnosis and tailored treatment strategies. The present review extracted 295 publications from the PUBMED database. Out of the 73 eligible studies, 55 miRNAs were assessed. A total of three of these miRNAs were not associated with any disease or cancer, whilst eight were associated with OC, albeit also associated with other diseases. The present review encompassed three dimensions: i) The role of miRNAs in treatment efficacy; ii) the use of miRNAs to enhance therapy outcomes; and iii) adjunctive strategies for improved treatment results. Furthermore, it offered insights into potential avenues for improving OC treatment using miRNA-based approaches.

Effect of sugar or sugar alcohol with different spatial structures on the stability of paclitaxel/HS15/Tween80 micelles: Based on micellization thermodynamics

Paclitaxel (PTX) is clinically recommended for the treatment of breast, ovarian and non-small cell lung cancer. This study delves into the impact of sugars (mannose or glucose) and sugar alcohols (mannitol or sorbitol) with varying spatial structures on the interfacial and thermodynamic behavior of the PTX/HS15/Tween80 micellar system. The research reveals that the presence of OH groups in sugars and sugar alcohols enhances hydrogen bonding force between surfactant and water, altering the critical micelle concentration (CMC) in solution and the surfactant’s arrangement at the interface, thus facilitating micelle formation and enhancing system stability. Dynamic light scattering (DLS) results show that the particle size of the PTX/HS15/Tween80 system is 11.69 nm, with micellar size showing a positive correlation with additive concentration. Sugar alcohols exhibit a more pronounced effect on increasing micelle size compared to sugars. Molecules featuring outward-facing OH groups demonstrating a greater ability to facilitate the formation of smaller micelle than those with inward-facing groups, emphasizing the influence of spatial structural differences. Stability experiments demonstrate that light transmission remains above 97 % in the system for 8 h after the addition of sugar, and the relative absorbance of PTX is maintained above 97 % within 6 h. Results from FD-B21 fluorescence probe release further confirm the positive impact of sugars and sugar alcohols on the stability of PTX/HS15/Tween80 micelles, highlighting stability differences based on molecules with distinct spatial structures. When OH groups on sugar or sugar alcohol molecules are more oriented in the same direction, intramolecular hydrogen bonds are formed, reducing spatial resistance and promoting the formation of micellar with smaller particle sizes. This process enhances physical stability by reducing inter-molecular collisions. In summary, the presence of sugars and sugar alcohols promotes micelle formation and boosts system stability, offering valuable insights for enhancing the stability of drug-loaded micelles.

Predicting Complete Cytoreduction with Preoperative [18F]FDG PET/CT in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis.

The cornerstone of ovarian cancer treatment is complete surgical cytoreduction. The gold-standard option in the absence of extra-abdominal metastases and intra-abdominal inoperable circumstances is primary cytoreductive surgery (CRS). However, achieving complete cytoreduction is challenging, and only possible in a selected patient population. Preoperative imaging modalities such as [18F]FDG PET/CT could be useful in patient selection for cytoreductive surgery. In our systematic review and meta-analysis, we aimed to evaluate the role of preoperative [18F]FDG PET/CT in predicting complete cytoreduction in primary and secondary debulking surgeries. Publications were pooled from two databases (PubMed, Mendeley) with predefined keywords "(ovarian cancer) AND (FDG OR PET) AND (cytoreductive surgery)". The quality of the included studies was assessed with the Prediction model Risk Of Bias Assessment Tool (PROBAST). During statistical analysis, MetaDiSc 1.4 software and the DerSimonian-Laird method (random effects models) were used. Primary and secondary cytoreductive surgeries were evaluated. Pooled sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated and statistically analyzed. Results were presented in forest plot diagrams and summary receiver operating characteristic (SROC) curves. Overall, eight publications were included in our meta-analysis. Four publications presented results of primary, three presented results of secondary cytoreductions, and two presented data related to both primary and secondary surgery. Pooled sensitivities, specificities, and positive and negative predictive values were the following: in the case of primary surgeries: 0.65 (95% CI 0.60-0.71), 0.73 (95% CI 0.66-0.80), 0.82 (95% CI 0.77-0.87), 0.52 (95% CI 0.46-0.59); and in the case of secondary surgeries: 0.91 (95% CI 0.84-0.95), 0.48 (95% CI 0.30-0.67), 0.88 (95% CI 0.81-0.93), 0.56 (95% CI 0.35-0.75), respectively. The PPVs of [18F]FDG PET/CT proved to be higher in cases of secondary debulking surgeries; therefore, it can be a valuable predictor of complete successful secondary cytoreduction.

Extracellular Vesicles in Ovarian Cancer: From Chemoresistance Mediators to Therapeutic Vectors.

Ovarian cancer (OC) remains the deadliest gynecological malignancy, with alarming projections indicating a 42% increase in new cases and a 51% rise in mortality by 2040. This review explores the challenges in OC treatment, focusing on chemoresistance mechanisms and the potential of extracellular vesicles (EVs) as drug delivery agents. Despite advancements in treatment strategies, including cytoreductive surgery, platinum-based chemotherapy, and targeted therapies, the high recurrence rate underscores the need for innovative approaches. Key resistance mechanisms include drug efflux, apoptosis disruption, enhanced DNA repair, cancer stem cells, immune evasion, and the complex tumor microenvironment. Cancer-associated fibroblasts and extracellular vesicles play crucial roles in modulating the tumor microenvironment and facilitating chemoresistance. EVs, naturally occurring nanovesicles, emerge as promising drug carriers due to their low toxicity, high biocompatibility, and inherent targeting capabilities. They have shown potential in delivering chemotherapeutics like doxorubicin, cisplatin, and paclitaxel, as well as natural compounds such as curcumin and berry anthocyanidins, enhancing therapeutic efficacy while reducing systemic toxicity in OC models. However, challenges such as low production yields, heterogeneity, rapid clearance, and inefficient drug loading methods need to be addressed for clinical application. Ongoing research aims to optimize EV production, loading efficiency, and targeting, paving the way for novel and more effective therapeutic strategies in OC treatment. Overcoming these obstacles is crucial to unlocking the full potential of EV-based therapies and improving outcomes for OC patients.

Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication.

Targeting multiple signaling pathways has been proposed as a strategy to overcome resistance to single-pathway inhibition in cancer therapy. A previous study in epithelial ovarian cancers identified hyperactivity of spleen tyrosine kinase (SYK) and epidermal growth factor receptor (EGFR), which mutually phosphorylate and activate each other. Given the potential for pharmacologic inhibition of both kinases with clinically available agents, this study aimed to assess the antitumor efficacy of both pharmacologic and genetic SYK and EGFR co-inhibition using a multifaceted approach to analyze the global phosphoproteome and chemoresistant ovarian cancer cell lines, patient-derived organoids, and xenograft models. Dual inhibition of SYK and EGFR in chemoresistant ovarian cancer cells elicited a highly synergistic antitumor effect. Notably, the combined inhibition strategy activated the DNA damage response, induced G1 cell cycle arrest, and promoted apoptosis. The phosphoproteomic analysis revealed that perturbation of SYK and EGFR signaling induced a significant reduction in both phosphorylated and total protein levels of cell division cycle 6 (CDC6), a crucial initiator of DNA replication. Together, this study offers preclinical evidence supporting dual inhibition of SYK and EGFR as a promising treatment for chemoresistant ovarian cancer that disrupts DNA synthesis by impairing formation of the prereplication complex. These findings warrant further clinical investigation to explore the potential of this combination therapy in overcoming drug resistance and improving patient outcomes.

Cell-free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer.

The emergence of targeted therapies has transformed ovarian cancer treatment. However, biomarker profiling for precision medicine is limited by access to quality, tumour-enriched tissue samples. The use of cell-free DNA (cfDNA) in ascites presents a potential solution to this challenge. In this study, next-generation sequencing was performed on ascites-derived cfDNA samples (26 samples from 15 human participants with ovarian cancer), with matched DNA from ascites-derived tumour cells (n = 5) and archived formalin-fixed paraffin-embedded (FFPE) tissue (n = 5). Similar tumour purity and variant detection were achieved with cfDNA compared to FFPE and ascites cell DNA. Analysis of large-scale genomic alterations, loss of heterozygosity and tumour mutation burden identified six cases of high genomic instability (including four with pathogenic BRCA1 and BRCA2 mutations). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Ascites cfDNA identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. This advocates for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy.

The role of DAPK2 as a key regulatory element in various human cancers: a systematic review.

Cancer is considered the uncontrolled growth and spread of cells into neighboring tissues, a process governed at the molecular level by many different factors, including abnormalities in the protein family's death-associated kinase (DAPK). DAPK2 is a member of the DAPK protein family, which plays essential roles in several cellular processes. DAPK2 acts as a tumor suppressor, interacting with several proteins, such as TNF, IFN, etc. during apoptosis and autophagy. Expression of DAPK2 causes changes in the structure of the cell, ultimately leading to cell death by apoptosis. In this essay, studies are obtained from Scopus, PubMed, and the Web of Science. According to these investigations, DAPK2 activates autophagy by interacting with AMPK, mTORC1, and p73. Furthermore, DAPK2 induces apoptosis pathway via interacting with the p73 family and JNK. In general, due to the vital role of DAPK2 in cell physiology and its effect on various factors and signaling pathways, it can be a potent target in the treatment of various cancers, including gastric, ovarian, breast, and other prominent cancers.

Identification and validation of genes associated with prognosis of cisplatin-resistant ovarian cancer

PurposeTo investigate the role of prognostic genes related to cisplatin resistance in ovarian cancer during disease progression.MethodThe gene expression profile of the NCI-60 cell line was acquired through comprehensive analysis of the GEO database accession GSE116439. We performed a thorough analysis of gene expression differences in samples from seven individuals exposed to cisplatin concentrations of 0 nM compared to seven samples exposed to 15000 nM over a 24-h period. Key genes were initially identified through LASSO regression, followed by their enrichment through differential gene function analysis (GO) and pathway enrichment analysis (KEGG). Subsequently, a prognostic risk model was established for these key genes. The prognostic model's performance was assessed through K-M survival curves and ROC curves. To examine the variance in immune cell infiltration between the high and low-risk groups, CIBERSORTx analysis was employed. Finally, validation of prognostic gene expression in cisplatin-resistant ovarian cancer was carried out using clinical samples, employing RT-qPCR and Western Blot techniques.ResultsA total of 132 differential genes were found between cisplatin resistance and control group, and 8 key prognostic genes were selected by analysis, namely VPS13B, PLGRKT, CDKAL1, TBC1D22A, TAP1, PPP3CA, CUX1 and PPP1R15A. The efficacy of the risk assessment model derived from prognostic biomarkers, as indicated by favorable performance on both Kaplan–Meier survival curves and ROC curves. Significant variations in the abundance of Macrophages M1, T cells CD4 memory resting, T cells follicular helper, and T cells gamma delta were observed between the high and low-risk groups. To further validate our findings, RT-qPCR and Western Blot analyses were employed, confirming differential expression of the identified eight key genes between the two groups.ConclusionVPS13B, TBC1D22A, PPP3CA, CUX1 and PPP1R15A were identified as poor prognostic genes of cisplatin resistance in ovarian cancer, while PLGRKT, CDKAL1 and TAP1 were identified as good prognostic genes. This offers a novel perspective for future advancements in ovarian cancer treatment, suggesting potential avenues for the development of new therapeutic targets.

Estrogen and progesterone receptor expression: Impacts on platinum sensitivity and survival outcomes in high‐grade serous ovarian cancer

AbstractBackgroundThis study aimed to explore the impact of patient‐specific factors on the effectiveness of platinum‐based chemotherapy in ovarian cancer patients. Specifically, we investigated the relationship between estrogen receptor (ER) and progesterone receptor (PR) expression levels and platinum sensitivity, and how this influenced treatment outcomes and prognosis. We conducted a survival analysis on patients who underwent surgical treatment for serous ovarian cancer and received platinum‐based adjuvant therapies.MethodsThis study was a retrospective observational analysis of 171 patients with high‐grade serous ovarian cancer. We extracted and analyzed the patients' clinical data, focusing on platinum sensitivity concerning hormone receptor expression. We also assessed survival outcomes based on receptor expression and platinum resistance.ResultsOur findings revealed that 78.4% (n = 134) of the patients were platinum‐sensitive, while 21.6% (n = 37) were platinum‐resistant. The expression of hormone receptors showed significant associations with platinum sensitivity, particularly among ER‐positive patients (p < 0.05). Age, disease stage, preoperative carbohydrate antigen 125 (CA125) levels, and residual tumor size were identified as notable factors influencing both progression‐free survival (PFS) and overall survival (OS). In terms of PFS, 88.5% of patients remained free from disease progression after one year, but this percentage dropped to 21% after five years. The average duration of PFS was 35.3 months. As for OS, 93.5% of patients were still alive after one year, but this percentage decreased to 50.5% after five years. The average survival duration was 64 months. Furthermore, platinum resistance was found to be a significant risk factor for disease progression, with a more than fivefold increase in risk (p < 0.001).ConclusionOur study identified disease stage progression, ER negativity, and platinum resistance as the primary factors influencing OS. We also found that ER and PR expression played a crucial role in determining the sensitivity to platinum‐based chemotherapy in patients with serous ovarian cancer.

Tandem mass tag-based quantitative proteomic analysis of metformin's inhibitory effects on ovarian cancer cells.

Metformin (MET), a type 2 diabetes treatment, has attracted increased attention for its potential antitumor properties; however, the precise mechanism underlying this activity remains unclear. Our previous in vivo and in vitro studies revealed MET's inhibitory effect on ovarian cancer, with the synergistic effects of MET and the MDM2 inhibitor RG7388 contributing to ovarian cancer treatment. This study further explores the mechanism underlying MET's inhibition of ovarian cancer. Following MET treatment, we analyzed the differentially expressed proteins in ovarian cancer cells using a tandem mass tag (TMT)-based proteomic approach coupled with bioinformatics. Using A2780 and SKOV3 ovarian cancer cells, we identified six upregulated and two downregulated proteins after MET treatment. Bioinformatics analysis revealed that these proteins predominately affect ovarian cancer cells by regulating iron ion transport, iron ion homeostasis, and mitochondrial and ribosomal functions. Validation via western blot confirmed MET-induced elevation of hydroxybutyrate dehydrogenase type 2 (BDH2) protein expression levels in A2780 and SKOV3 cells. Overall, our findings suggest that combining MET with other metabolic drugs, such as iron-chelating agents and mitochondrial inhibitors, may result in synergistic antitumor effects, thereby offering novel avenues for ovarian cancer treatment development.

The Thoracic Surgeon: “The Icing on the Cake” in the Treatment of Epithelial Ovarian Cancer

In patients with ovarian cancer, VATS should be used to exclude or confirm the presence of supradiaphragmatic disease and possibly remove it completely. The simultaneous use of laparoscopy and VATS allows for an accurate selection of patients to be sent, in a very short time, to primary surgery or neoadjuvant chemotherapy. Therefore the thoracic surgeon should be part of the multidisciplinary team in every ovarian cancer center

Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial.

The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. This investigator-initiated trial was funded by Merck.

Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi)

ObjectivePoly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety...

Interleukine-10 in ovarian cancer.

Interleukins serve as communicating molecules between cells, mediating key interactions in the tumor microenvironment (TME) between immune cells and non-immune cells. Interleukin-10 (IL-10), a multifunctional cytokine with multiple properties, has been extensively studied in various aspects of immunology and cancer biology. IL-10 is pleiotropic, promotes cytotoxicity, yet inhibits antitumor-responses. In recent years, the role of IL-10 in ovarian cancer (OC) progression and treatment has gained significant scientific attention, elucidating the signaling pathways triggered by IL-10 action. OC, the leading cause of gynecologic cancer-related deaths, is characterized by ascites, which hosts an intricate TME that is not responsive to treatment by immune checkpoint inhibition. IL-10, known for its immunosuppressive and anti-inflammatory properties, plays a complex role in OC progression, immune modulation, and therapeutic response and has a potential therapeutic property as a target and as an effector. As the literature of basic science research studying the role of IL-10 in the TME of OC scopes a few decades and some data is contrasting, it is important to review the literature and provide concise input derived from it. This review aims to provide a comprehensive overview of the current understanding of IL-10 in OC, highlighting its influence on tumor growth, immune evasion, and potential as a therapeutic target.

An oncolytic adenovirus co-expressing a bi-specific T cell engager and IL-2 for the treatment of ovarian cancer

An oncolytic adenovirus co-expressing a bi-specific T cell engager and IL-2 for the treatment of ovarian cancer

A novel selective FAK inhibitor E2 inhibits ovarian cancer metastasis and growth by inducing cytotoxic autophagy

Ovarian cancer (OC) is the deadliest form of the gynecologic malignancies and effective therapeutic drugs are urgently needed. Focal adhesion kinase (FAK) is overexpressed in various solid tumors, and could serve as a potential biomarker of ovarian cancer. However, there are no launched drugs targeting FAK. Hence, the development of the novel FAK inhibitors is an emerging approach for the treatment of ovarian cancer. In this work, we characterized a selective FAK inhibitor E2, with a high inhibitory potency toward FAK. Moreover, E2 had cytotoxic, anti-invasion and anti-migration activity on ovarian cancer cells. Mechanistically, after treatment with E2, FAK downstream signaling cascades (e.g., Src and AKT) were suppressed, thus resulting in the ovarian cancer cell arrest at G0/G1 phase and the induction of cytotoxic autophagy. In addition, E2 attenuated the tumor growth of PA-1 and ES-2 ovarian cancer subcutaneous xenografts, as well as suppressed peritoneal metastasis of OVCAR3-luc. Furthermore, E2 exhibited favorable pharmacokinetic properties. Altogether, these findings demonstrate that E2 is a selective FAK inhibitor with potent anti-ovarian cancer activities both in vivo and in vitro, offering new possibilities for OC treatment strategies.

Fabrication of co-delivery liposomal formulation incorporating carmustine and cabazitaxel displays improved cytotoxic potential and induced apoptosis in ovarian cancer cells

Ovarian cancer is the primary cause of death from cancer in female patients. The existing treatments for ovarian cancer are restricted and ineffective in achieving a cure for the disease. To address this issue, we provide a novel approach to treating ovarian cancer by utilizing a liposomal carrier that effectively delivers the chemotherapeutic drugs carmustine (BCNU) and cabazitaxel (CTX). Initially, the combined impact of BCNU and CTX was confirmed, revealing that this impact reaches its maximum at a ratio of 1:2 mol/mol (BCNU/CTX). After that, the BC-Lipo co-delivery system was developed, which has a high capability for loading drugs (97.48% ± 1.14 for BCNU, 86.29% ± 3.03 for CTX). This system also has a sustained release profile and a beneficial long-circulating feature. The accumulation of BC-Lipo in tumors was dramatically enhanced compared to the accumulation of the free drug. Furthermore, BC-Lipo demonstrated similar levels of cytotoxicity to free BCNU and CTX (BCNU/CTX) when tested on HeLa cells in an in vitro model. Biochemical staining methods investigated the cancer cell’s morphological examination. The apoptosis was confirmed by FITC-Annexin-V/PI staining by flow cytometry analysis. In addition, the investigation of fluorescence and protein markers examined the apoptosis mechanistic pathway, and the results indicated that BC-Lipo induced apoptosis due to mitochondrial membrane potential variation. This proof-of-concept study has established the probability of these BCNU-CTX combined treatments as active drug delivery nanocarriers for poorly soluble BCNU and CTX.

Cationic liposomes overcome neutralizing antibodies and enhance reovirus efficacy in ovarian cancer

Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MβCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.

Past and present: a bibliometric study on the treatment of recurrent ovarian cancer.

Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment. Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) co-occurrence of keywords. A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis). Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC.