Treatment Of Ovarian Cancer Research Articles

Enhanced anti-ovarian cancer efficacy with MSLN-chimeric antigen receptor T cells secreting anti-CD39 antibody.

e17553 Background: The effectiveness of chimeric antigen receptor (CAR) T cell therapy directed at mesothelin (MSLN) in solid tumors, such as ovarian cancer, is hindered by the immunosuppressive tumor microenvironment (TME), where adenosine plays a crucial role in impairing CAR-T cell function. Preclinical and clinical studies have demonstrated that targeting CD39, a pivotal enzyme catalyzing the conversion of extracellular ATP into adenosine, yields significant antitumor effects. Therefore, combining MSLN CAR-T with an anti-CD39 antibody emerges as a potential therapeutic strategy against cancer. Methods: We have previously designed OriA631, an antibody antagonist targeting CD39 in VHH format. Our preclinical investigation has highlighted the outstanding potential of OriA631, showcasing superior performance in binding affinity, effective inhibition of CD39 enzyme activity, and remarkable in vivo high anti-tumor efficacy. Subsequently, we undertook further engineering of MSLN CAR-T cells to secrete the VHH component of OriA631 (MSLN CAR-T-CD39-VHH) and systematically assessed its antitumor effects in NSG mice. Results: Our data reveals that MSLN CAR-T cells exhibit a significant upregulation of CD39 upon activation by ovarian cancer cells in both in vitro and in the tumor microenvironment (TME). To assess the combined effect of MSLN CAR-T with anti-CD39, B-NDG mice were subcutaneously inoculated with 3x10^6 ovarian cancer cells (SKOV3-MSLNhi-CD39hi). Subsequently, different T cells (1x10^7 cells/mouse) were injected when the tumor reached around 80 mm³, and the groups were divided into Mock T, MSLN CAR-T, MSLN CAR-T-CD39-VHH, and MSLN CAR-T in combination with locally injected CD39 Ab (OriA631). The data demonstrated that MSLN CAR-T inhibited tumor growth from approximately 1000mm³ (Mock T group) to 300mm³ at day 30 relative to T cell injection. Tumors in the MSLN CAR-T in combination with OriA631 group were around 100mm³, suggesting a significant combination anti-tumor efficacy of MSLN CAR-T in conjunction with CD39 targeting. Furthermore, MSLN CAR-T-CD39-VHH, where MSLN CAR-T cells secrete the VHH component of OriA631, completely eliminated the tumor at day 18 with no relapse during the experimental period. This result underscores the superior anti-tumor efficacy of MSLN CAR-T-CD39-VHH, with the high level of VHH component of CD39 Ab observed in the TME. Importantly, the low or undetectable level of VHH component of CD39 Ab in the serum also indicates the safety of the product. Conclusions: Our study introduces the innovative therapeutic agent MSLN CAR-T-CD39-VHH, showcasing superior anti-tumor efficacy and the potential for reduced antibody-associated side effects. These findings strongly endorse the application of MSLN CAR-T-CD39-VHH as a promising and impactful therapeutic approach for the treatment of ovarian cancer.

TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation.

Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co-immunoprecipitation and western blotting. TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

Diagnostic, prognostic, and immunological roles of CDSN in ovarian cancer

Globally, ovarian cancer (OC) ranks as a principal cause of cancer-related mortality in females. Immunotherapy has revolutionized the treatment of OC, but the efficacy of immunotherapy is often limited by different immune microenvironments. The objective of this research was to pinpoint and validate candidate genes with potential value as diagnostic and prognostic biomarkers and therapeutic targets in OC. Data on genes associated with gene mutation, prognostic survival, and immune infiltration in OC were procured from the Cancer Genome Atlas (TCGA). Gene differential analysis, mutation site analysis, prognosis and survival analysis, and functional and signaling pathway enrichment analysis were conducted to identify and evaluate key genes. The genes were further investigated using immune infiltration analysis, receiver operating characteristic curves, and immunohistochemistry. The impact of CDSN on OC cell proliferation was investigated utilizing CCK-8, colony formation, and apoptosis detection assays. We identified a set of genes (CDSN, WARS, and CD38) that were highly expressed in OC and significantly associated with mutations and prognosis. Immune infiltration analysis and immunohistochemistry results indicated a correlation with immune infiltration in the tumor microenvironment, particularly in antigen-presenting cells. Receiver operating characteristic curve analysis demonstrated the diagnostic potential of these three genes in OC, with all three genes showing the area under the curve (AUC) above 0.8. In vitro studies suggested that knocked down CDSN expression resulted in a marked lower in the proliferative capacity of OC cells. The candidate gene CDSN identified through bioinformatics analysis and in vitro experiments is associated with mutation and immune infiltration, showing promise as a diagnostic and prognostic biomarker, as well as a therapeutic objective in OC.

Optimizing Ovarian Cancer Treatment and Prevention Through Parallel Germline and Somatic Genetic Testing.

Optimizing Ovarian Cancer Treatment and Prevention Through Parallel Germline and Somatic Genetic Testing.

Charlson’s comorbidity and remission outcomes in women diagnosed with epithelial ovarian cancer.

e17562 Background: Several prior studies have examined the role of comorbidity on overall survival in ovarian cancer (OC) patients and reported an association between comorbidity and inferior overall survival. However, it is unclear if the inferior survival was solely due to the excess mortality from the comorbidities, or that the comorbidities can impact OC treatment outcomes. Our objective was to determine whether pre-existing Charlson comorbidity index (CCI) was associated with lower likelihood of achieving complete remission. Methods: This retrospective cohort study included patients diagnosed with OC of epithelial subtype between 01/01/2017-06/30/2021 at a large integrated healthcare delivery system in the United States. OC patients were identified from the healthcare system’s cancer registry or via chart review of those with the ICD-10 diagnosis code. Patient’s CCI was determined based on data from the 12-month window prior to OC diagnosis. Patients’ remission outcomes, including complete remission and clinical remission (complete + partial remission) were ascertained via chart review, considering physician’s assessment, CA125 value and imaging evidence. Data on potential confounders (pandemic period, age, race/ethnicity, FIGO stage, prior length of membership, and time to treatment) were obtained from the healthcare system’s electronic medical records. Bivariate and multivariable modified Poisson regressions adjusting for potential confounders were used to evaluate the associations between CCI and achieving complete remission or clinical remission by end of therapy. Results: A total of 799 patients diagnosed with OC were included in our study. Overall, the cohort was racially/ethnically diverse with 46.2% White, 33.8% Hispanic, 12.4% Asian, and 7.6% Black patients. In the crude analysis, those with CCI score=1 and CCI≥2 had lower likelihood of achieving complete remission, compared with those with CCI=0 (no Charlson comorbidity) [RR= 0.84 (0.76-0.93) and RR=0.72 (0.64-0.81), respectively]. In the multivariable analysis, those with CCI=1 and CCI≥2 continued to have lower likelihood of achieving complete remission, compared with those with CCI= 0 [RR= 0.84 (0.77-0.92) and RR=0.81 (0.72-0.91), respectively]. Similar findings were observed for clinical remission, although the associations were attenuated: RR= 0.95 (0.89-1.01) for CCI=1 and RR=0.92 (0.86-1.00) for CCI≥2 vs. CCI=0. Conclusions: Having Charlson comorbidity was associated with lower likelihood of achieving complete remission in OC patients. This finding suggest that pre-existing comorbidities may contribute to inferior survival via, at least in part, adversely affecting the likelihood of achieving complete remission. The potential mechanisms underlying this association should be further studied to inform patient management.

A novel lactylation-related gene signature for effectively distinguishing and predicting the prognosis of ovarian cancer.

Lactylation has been found to regulate several types of biological processes in cancer. However, there is limited research on lactylation-related genes in predicting the prognosis of ovarian cancer (OC). This study aimed to explore the functional roles of lactylation-related genes in OC. Based on TCGA database, we obtained RNA sequencing data and clinical characteristics of patients with OC. Fourteen lactylation-related genes were screened for bioinformatic analysis in OC. Tumor classification of OC was constructed via a consistency cluster analysis. We examined the prognosis, immune-cell infiltration, and immunotherapy in relation to a lactylation-related model for OC. A total of 707 prognostic genes and 14 key lactylation-related genes (SNRPA1, MPHOSPH6, POLDIP3, RB1, AHNAK, MAGOHB, CALM1, EP300, HDAC1, HDAC2, HDAC3, SIRT1, SIRT2, and SIRT3) were identified in TCGA-OC patients. Based on 14 genes involved in lactylation, TCGA-OC patients were split into low-risk (G1) and high-risk (G2) groups. Downregulated differentially expressed genes (DEGs) in the low-risk G1 group were associated with thermogenesis, oxidative phosphorylation, neutrophil extracellular trap formation, and interleukin 17 (IL-17) signaling pathway, whereas upregulated DEGs were associated with proteoglycans in cancer, focal adhesion, Wnt signaling pathway, extracellular matrix (ECM)-receptor interaction, and the adherens junction. The immune activity of the low-risk G1 group was lower than that of the high-risk G2 group. Gemcitabine, bleomycin, and doxorubicin had lower half-maximal inhibitory concentration (IC50) values in the high-risk G2 patients with OC, while cisplatin and paclitaxel had higher IC50 values compared to the low-risk G1 patients. The prognosis of patients with OC was also predicted with the help of an eight-lactylation-related gene prognostic model, comprising SNRPA1, MPHOSPH6, POLDIP3, RB1, HDAC1, CALM1, HDAC2, and SIRT2. The lactylation-related genes are closely related to tumor classification and immunity in patients with OC. There was good prognostic predictive performance for OC based on a lactylation-related signature. Our findings may offer new insights into the diagnosis and treatment of OC.

Aberrant angiogenic signaling pathways: Accomplices in ovarian cancer progression and treatment

Ovarian cancer is one of the most common malignant tumors in women, and treatment options are limited. Despite efforts to adjust cancer treatment models and develop new methods, including tumor microenvironment (TME) therapy, more theoretical support is needed. Increasing attention is being given to antiangiogenic measures for TME treatment. Another important concept in ovarian cancer TME is angiogenesis, where tumor cells obtain nutrients and oxygen from surrounding tissues through blood vessels to support further expansion and metastasis. Many neovascularization signaling pathways become imbalanced and hyperactive during this process. Inhibiting these abnormal pathways can yield ideal therapeutic effects in patients, even by reversing drug resistance. However, these deep TME signaling pathways often exhibit crosstalk and correlation. Understanding these interactions may be an important strategy for further treating ovarian cancer. This review summarizes the latest progress and therapeutic strategies for these angiogenic signaling pathways in ovarian cancer.

DC-derived CXCL10 promotes CTL activation to suppress ovarian cancer

This study investigates the role of dendritic cells (DCs), with a focus on their CXCL10 marker gene, in the activation of cytotoxic T lymphocytes (CTLs) within the ovarian cancer microenvironment and its impact on disease progression. Utilizing scRNA-seq data and immune infiltration analysis, we identified a diminished DC presence in ovarian cancer. Gene analysis pinpointed CXCL10 as a key regulator in OV progression via its influence on DCs and CTLs. Prognostic analysis and in vitro experiments substantiated this role. Our findings reveal that DC-derived CXCL10 significantly affects CTL activation and proliferation. Reduced CXCL10 levels hinder CTL cytotoxicity, promoting ovarian cancer cell migration and invasion. Experimental studies using animal models have provided further evidence that the capacity of CTLs to suppress tumor development is significantly diminished when treated with DCs that have low expression of CXCL10. Dendritic cell-derived CXCL10 emerges as a pivotal factor in restraining ovarian cancer growth and metastasis through the activation of cytotoxic T lymphocytes. This study sheds light on the crucial interplay within the ovarian cancer microenvironment, offering potential therapeutic targets for ovarian cancer treatment.

Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.

Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.

OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer.Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively.Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n=311 [87.6%]; Brazil: n=1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line.Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

Mechanistic analyses reveal that Pueraria montana var. lobata (Willd.) is effective in inhibiting ovarian cancer progression.

Ovarian cancer (OC) is a common malignancies of the female genitalia. P. montana var. lobata (Willd.), a herb with anti-tumor effects, is widely used in the clinical treatment of ovarian cancer (OC), but the ingredients and molecular mechanism of action remains to be explored. In this study, we extracted the main active ingredients of P. montana var. lobata (Willd.) from the TCMSP database, and predicted its potential targets of action against OC from the DisGeNET and GeneCards databases. Protein-protein interaction (PPI) was constructed using the STRING database, while pathway enrichment analyses were performed using the DAVID database. Next, we generated an Ingredient-Target-Pathway network using Cytoscape 3.7.2, then processed the key targets of action and main active ingredients for molecular docking.The results showed that seven active ingredients of P montana var. lobata (Willd.) were associated with treating for OC, namely beta-sitosterol, coumestrol, daidzein, formononetin, genistein, puerarin and scoparone, two important targets Casp3 and Jun, and signaling pathways of P. montana var. lobata (Willd.) against the progression of OC. TUNEL staining, enzyme-linked immunosorbent assay (ELISA), and Western blot assays, the pharmacodynamic effect of puerarin in the treatment of OC and the major targets were verified. Animal experiment demonstrated that application of puerarin at different times of modeling not only upregulated expression of Casp3, Smac, and c-jun proteins, but also promoted apoptosis in tumor cells, hence inhibiting progression of OC. This study demonstrates that P. montana var. lobata (Willd.) can thereby induce apoptosis in tumor cells and inhibit malignant progression through activating expression of Casp3, smac, and c-jun proteins to regulate related apoptosis pathways, as validated by network pharmacology predictions and animal experiments, and can be verifed by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.

Transcriptome profiling and characterization of peritoneal metastasis ovarian cancer xenografts in humanized mice

Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.

Global research trends in liquid biopsy for ovarian cancer from 1999 to 2023: A 25-year bibliometric analysis

BackgroundOvarian cancer (OC) is a major cause of gynecological cancer-related death in the world. Liquid biopsy has shown great potential in improving the ovarian cancer detection and treatment. The aim of this study is to explore the previous studies, current hotspots, and future trends of liquid biopsy for OC from a bibliometric perspective. MethodsArticles on liquid biopsy in the field of OC were collected from Web of Science (Clarivate Analytics). Subsequently, bibliometric and visual analyses was conducted using bibliometrix, VOSviewer, CiteSpace, and Microsoft Excel. ResultsA total of 504 scientific papers were retrieved over a 25-year period, of which 285 papers were in the language of English. China has the highest number and other papers came from 41 countries or regions. The journal with the highest publication count was Cancers. There were 2013 authors in total, and Kasimir-Bauer S emerged as the most productive author. The key words that are still exploding are recurrence, predictive value and survival. ConclusionResearch on liquid biopsy is booming in the field of OC. This article comprehensively elucidates the subject matter over recent years, and points out emerging trends for in-depth exploration.

Luminescent nanotherapeutics system for Real-Time imaging and Membrane-Mitochondria stepwise targeted drug delivery in ovarian cancer

Considerable attention has been devoted to developing anti-cancer treatments targeted mitochondria. However, there is a dearth of literature on using luminescent metal–organic frameworks for the transportation of anti-cancer drugs to organelles. A luminescent nanotherapeutic platform known as UiO-DOX@FA/TPP has been engineered with a membrane-mitochondrial stepwise targeting strategy for the delivery of doxorubicin (DOX). DOX administration caused mitochondrial dysfunction, increased Caspase-3 activity, and cell apoptosis. The UiO-DOX@FA/TPP system improved drug sensitivity, requiring only 10.8 % of the free DOX dose. It showed strong anti-tumor effects in vivo, with over 98 % tumor growth inhibition and commendable biocompatibility. The system also enabled in vivo imaging by emitting fluorescence at around 500 nm, highlighting its transport and targeted distribution to tumor sites. Furthermore, treating cells with UiO-DOX@FA/TPP nanosystem led to extensive gene expression changes, primarily enriched in Ca2+ signaling and autophagy regulation. The stepwise targeted luminescent UiO-DOX@FA/TPP nanosystem allow for the precise identification and delineation of ovarian cancer boundaries, monitoring of drug transport in real-time, and targeted delivery to mitochondria for inducing apoptosis. This innovative approach provides a theoretical and methodological basis for integrating ovarian cancer diagnosis and treatment.

Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/β‑catenin pathway.

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial‑mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit‑8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S‑phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/β‑catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/β‑catenin pathway to induce anti‑metastatic, anti‑invasive and anti‑EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers.

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.

Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1–9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1–3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 μM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Primary cytoreductive surgery followed by chemotherapy compared to neoadjuvant chemotherapy followed by cytoreduction as a treatment for stage III and IV ovarian cancer (literature review)

Standard treatment for advanced ovarian cancer (OC) consists of a combination of chemotherapy and cytoreductive surgery, but practice varies depending on the order of these 2 procedures: neoadjuvant chemotherapy followed by interval debulking surgery or primary cytoreduction followed by adjuvant chemotherapy. The aim of the work is to evaluate methods of treatment of OC of stages III, IV according to FIGO.The literature review includes publications in English from the PubMed, CochraneLibrary and Google Scholar databases on the use of neoadjuvant therapy and primary cytoreduction in late stages of OC (FIGO III–IV). 6 randomized controlled trials, 8 meta-analyses, 8 systematic reviews, 1 case report were identified. Data from publications were distributed according to the criteria for assessing the effectiveness of the treatment: overall and relapse-free survival, perioperative complications, quality of life of patients and the grade of cytoreduction.Neoadjuvant chemotherapy + interval debulking surgery is not inferior to primary debulking surgery + adjuvant chemotherapy in terms of survival outcomes in selected patients, but treatment with neoadjuvant chemotherapy + interval debulking surgery improves perioperative outcomes and optimal cytoreduction rates. It is needed to focus on finding optimal criteria for selecting patients in both groups in future studies of this issue. It is necessary to take into account X-ray, histological studies, the molecular subtype of the tumor, the patient’s condition, the qualifications of the surgical team, the drugs included in chemotherapy.

Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital.

Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76-43.23), and median PFS was 8 months (95% CI: 2.48-13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1-2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.