Search Results (727)

Vernonia calvoana (VC), a commonly used medicinal plant in West Africa, has been shown by our research team to inhibit the proliferation of OVCAR-3 ovarian cancer cells through mechanisms involving oxidative stress, DNA damage, and S-phase cell cycle arrest. The objective of the current study was to elucidate the intrinsic apoptotic mechanisms triggered by VC fraction seven (VCF7). OVCAR-3 cells were treated with VCF7 (0, 8, 16, and 32 μg/mL) for a duration of 48 h. Apoptosis was assessed using Annexin V/Propidium Iodide (PI) staining followed by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was assessed through JC-1 staining and confocal microscopy, while chromatin condensation was analyzed using DAPI staining. DNA fragmentation was examined by agarose gel electrophoresis. Caspase 3 activity was measured using flow cytometry. Protein expression levels of p53, Bcl-2, cytochrome c, caspase-9, and caspase-3 were determined by Western blot analysis, and mRNA expression levels of p53 and Bcl-2 were evaluated using qRT-PCR. VCF7 induced apoptosis in a concentration-dependent manner. Analysis using Annexin V/PI indicated an increase in apoptotic cell populations from 10.5% to 30%, along with a rise in necrotic cells from 7% to 50% across treatment concentrations. A modest, concentration-associated decrease in mitochondrial membrane potential was recorded (0.96-, 0.88-, and 0.85-fold at 8, 16, and 32 μg/mL, respectively; p < 0.05). DAPI staining validated the concentration-dependent chromatin condensation and nuclear fragmentation. The analysis of DNA fragmentation showed progressive internucleosomal degradation, appearing as a smear pattern with distinct fragments at elevated concentrations, indicative of concurrent apoptotic and necrotic cell death. The activation of caspase-3 reached a peak of 28% at 16 μg/mL. Western blot analysis indicated an upregulation of p53, a downregulation of Bcl-2, an increase in total cytochrome c protein levels, and an increased expression of caspase-9 and caspase-3 in a concentration-dependent manner. These findings were corroborated at the transcriptional level by qRT-PCR, which showed increased p53 mRNA and decreased Bcl-2 mRNA expression. Taken together, these results underscore the potential of VCF7 as a promising plant-derived anticancer agent and support the need for further preclinical and clinical studies in ovarian cancer. Full article

Background/Objectives: Ovarian cancer is a prevalent gynecological malignancy with high mortality rates worldwide. Harmine hydrochloride (HMH), a tricyclic β-carboline alkaloid derived from the seeds of the medicinal plant Peganum harmala L., has demonstrated anti-tumor activity. This study investigated the effect of HMH on ovarian cancer and elucidated its underlying molecular mechanism. Methods: The anti-ovarian cancer effects of HMH were evaluated using the CCK-8 assay, cell cycle and apoptosis analyses, as well as a cell migration assay. The RNA-seq was utilized to explore the mechanisms of HMH. Western blot, qRT-PCR and IF were employed for further validation of the expression levels of relevant molecules. The Kaplan–Meier (KM) curve was conducted to evaluate the possible link between NFAT1 levels and the prognosis of ovarian cancer. The biological functions of NFAT1 were explored through siRNA knockdown experiments. Auto-dock molecular docking and DARTS were used to analyze the direct interaction between HMH and NFAT1. The in vivo efficacy of HMH was examined through bioluminescence imaging of intraperitoneal xenografts established with luciferase-expressing HEY cells. Results: HMH induced apoptosis, arrested the cell cycle, and suppressed migration of HEY and CAOV3 cells. NFAT1 was highly expressed in the nucleus of HEY and CAOV3 cells and promoted ovarian cancer progression. In addition, low NFAT1 expression levels had significantly improved overall survival and progression-free survival. Moreover, HMH reduced NFAT1 expression and reversed Ion-induced NFAT1 levels in ovarian cancer cell nuclei. The molecular docking and DARTS results suggested that HMH binds to NFAT1. Treatment with MG132 effectively blocked HMH-induced NFAT1 downregulation. Furthermore, HMH effectively blocked intraperitoneal xenograft development, and extended the life span of animals bearing HEY/Luc cells, when used alone or in combination with CDDP. Conclusions: The research indicated that HMH exerts anti-ovarian cancer effects, at least in part, by targeting NFAT1. Additionally, our research revealed that NFAT1 promotes ovarian cancer progression, and plays a significant role in HMH’s anti-cancer activity. These results may aid in the development of novel candidates for ovarian cancer and identify a new target for ovarian cancer treatment. Full article

Metastasis, chemoresistance, and tumour recurrence are facilitated by cancer stem cells (CSCs), a small subpopulation of cells capable of regenerating a primary tumour while maintaining the tumour’s genetic and phenotypic features. CSCs can be identified by the expression of specific markers; however, the CSC population in ovarian clear cell carcinoma (OCCC), a rare histotype of ovarian cancer, remains poorly defined. Given the well-established role that CSCs play in cancer progression and metastasis, it is critical to identify reliable markers of CSCs in OCCC. Here, we endeavoured to determine whether ALDH1 expression could be used to define OCCC stem cells in OCCC cell lines using a variety of methods including assessing ALDH1A1 expression in spheroids generated under distinct conditions. We also generated and used chemo-resistant cell lines to assess the enrichment of cancer stem cells. Human OCCC cell lines were enriched for CSCs using selective culture conditions and drug resistance methods. CSC-enriched spheroids demonstrated increased expression of stemness markers NANOG and SOX2, while ALDH1A1 expression was enriched only in drug-resistant cell lines, relative to parental cell lines. RNA-seq analyses of CSC-media-derived spheroids versus standard media spheroids provided novel data supporting CSC enrichment and identified transcription factors induced by CSC media. These findings highlight the ambiguous role of ALDH1A1 as a CSC marker in OCCC and demonstrates the utility of CSC enrichment methods for identifying CSC populations in OCCC cell lines. Full article

Background/Objectives: First-line maintenance is established in advanced epithelial ovarian cancer (AEOC), but management remains uncertain for patients without a BRCA mutation or homologous recombination deficiency (HRD)-positive disease. We assessed real-world use of bevacizumab, poly(ADP-ribose) polymerase (PARP) inhibitors and active surveillance in France (FR), Germany (DE), Italy (IT), Spain (ES) and the United Kingdom (UK). Methods: Anonymised physician-reported charts were analysed from a retrospective, non-interventional online survey conducted by AplusA Healthcare Marketing Research. Eligible patients had stage III–IV AEOC, no known BRCA-mutated or HRD-positive disease, no progression after first-line platinum chemotherapy, and started maintenance therapy or active surveillance between November 2024 and March 2026. Treatment allocation was compared by chi-square testing. Multinomial logistic regression assessed whether country remained associated with strategy after adjustment for clinical and disease characteristics. Results: Among 3293 patients, 1295 (39.3%) received bevacizumab, 1087 (33.0%) niraparib, 158 (4.8%) rucaparib, 477 (14.5%) active surveillance and 276 (8.4%) other therapy. Treatment allocation differed by country (χ² = 725.4, df = 16, p < 0.001). Bevacizumab was most frequent in FR and least frequent in the UK; niraparib was most frequent in ES and the UK; active surveillance was most common in the UK and IT. In the adjusted model, country was the strongest factor associated with strategy (likelihood-ratio χ² = 550.1, df = 8, p < 0.001). Conclusions: First-line maintenance practice in AEOC without an actionable BRCA/HRD biomarker varies substantially across European countries. These differences may partly reflect national access, reimbursement, clinical practice and other unmeasured country-level factors. Outcome-based real-world studies are needed to clarify the best strategy. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article

Ovarian cancer exhibits clinical heterogeneity; reliable prognostic stratification remains challenging despite extensive biomarker research. We performed an integrative analysis of transcriptomic and proteomic data to identify prognostically distinct molecular clusters in ovarian cancer. Using The Cancer Genome Atlas dataset, RNA sequencing and reverse–phase protein array data from 146 overlapping samples were analyzed. Genes (n = 150) and proteins (n = 67) showing nominal associations with overall survival (p < 0.05) were integrated; k–means clustering identified two patient clusters with highly significant differences in survival (p = 8.59 × 10⁻¹⁵). The SAR2 and ACTN4 genes and their corresponding protein expression levels showed high correlations among the significant genes and proteins (correlation coefficients > 0.80). Gene set enrichment analysis revealed that genes regulated by the PAX2 and BCL6 transcription factors were significantly enriched. The identified clusters were validated across six independent public transcriptomic datasets comprising 617 patients; consistent survival separation was observed between the patient clusters (p < 0.05). Clustering based on immunohistochemistry–derived expression profiles of nine proteins in an independent patient cohort demonstrated a significant difference in survival (p = 0.04). Integrative analysis of multi–omics data provided robust prognostic stratification in ovarian cancer while capturing the underlying molecular and biological features. Full article

Environmental exposure to pesticides is considered a risk factor for gynecological cancers, contributing to their onset and progression through various mechanisms. This narrative review investigates the role of different pesticides in the development and progression of ovarian, endometrial, and cervical cancers, and provides a comprehensive synthesis of epidemiological findings along with molecular mechanisms, highlighting carcinogenic pathways, conflicting findings, and potential therapeutic implications. Relevant epidemiological and experimental studies published between 2000 and 2025 were identified through searches of major scientific databases. Various pesticides, particularly organochlorines, contribute to gynecological cancers through mechanisms such as estrogen mimicry, DNA damage, oxidative stress, increased pro-inflammatory cytokines, and disruption of cellular signaling pathways. However, most studies found no significant association between certain pesticides, such as Triazines and Atrazine, and gynecological cancers. Furthermore, some pesticides, like Carbendazim, exhibit a dual role; while carcinogenic, they can also serve therapeutic purposes in cancer treatment when utilized with nanotechnology. Overall, pesticide exposure is a significant factor in the development and progression of women’s cancers, although the strength of the evidence varies across pesticide classes. Despite numerous studies, contradictory findings necessitate further research to clarify causal relationships. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Background: The neutrophil-to-lymphocyte ratio (NLR) has been the focus of extensive research in recent years as an inexpensive inflammatory biomarker with prognostic value in oncology, but its relationship with tumor grade across solid malignancies remains uncertain. Methods: This systematic review evaluated original clinical studies reporting the association between peripheral blood NLR and histological tumor grade in solid tumors. PubMed and Web of Science were searched using Boolean strategies, and eligible full-text studies were synthesized qualitatively because of heterogeneity in tumor type, grading system, NLR threshold, and statistical reporting. Results: The qualitative synthesis included 13 retrospective primary studies comprising 5394 patients. Eight studies reported statistically significant associations between higher NLR and higher tumor grade or poorer differentiation, most consistently in bladder cancer and in single studies of prostate cancer, soft tissue sarcoma, renal cell carcinoma, pancreatic cancer, breast cancer, and colorectal cancer with synchronous liver metastases. Four studies reported no statistically significant grade-related association, mainly in heterogeneous breast cancer and ovarian cancer cohorts, whereas a small colorectal adenocarcinoma cohort study showed a non-significant positive trend. Conclusions: The available evidence suggests a possible relationship between systemic inflammation and tumor grade in selected malignancies, but the evidence remains preliminary, tumor-specific, retrospective, and vulnerable to confounding. NLR should not be interpreted as a surrogate for histological grade. Full article

The objective of this research is the development of a copper-based optical sensor for the detection of ovarian cancer marker CA 125 synthesized using low-temperature plasma. Optical materials produced with metals show unique advantages due to their ability to interact with light. There are different methods currently used for the synthesis of optical materials that can be associated with longer processing times and low material yield. The novelty of this study is the development of copper-based optical material (CuPy) using low-temperature plasma and subsequent modification for the detection of CA 125. Introduction: Plasma consists of a mixture of fully and partially ionized gas. It comprises diverse, highly energized species of atoms, ions, electrons, excited molecules, and charged species. These energized species are used to create new materials, for surface modifications, and in medical applications. Plasma can create a controlled environment for the creation of novel materials. Using low-temperature plasma, it will be possible to have precise control of the chemical composition and structure due to the creation of excited molecules, ions, and free radicals. Method: The CuPy material was synthesized using radio-frequency-assisted low-temperature plasma. Prior to synthesis, the plasma chamber was cleaned using radio frequency (RF) plasma without any reagents or gases. RF plasma was used for the synthesis of CuPy for 10 min and subsequent hydrogen plasma (50 sccm) for another 10 min. Two types of products were extracted from the chamber (one in water and another in methanol). These two products were analyzed using UV–visible absorbance spectroscopy, fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). The methanol extracted samples were further modified with CA 125 antibody. Zeta potential measurements were performed to confirm the binding of the CA 125 antibody to the sensor. The sensing efficacy of the sensor towards CA 125 antigen was monitored using fluorescence spectroscopy. Results: The absorbance spectrum of methanol extracted CuPy shows absorbances around 251 nm, 282 nm, and 339 nm. The extracted product exhibited a red edge excitation emission in the visible region. The elemental composition and oxidation state of the sample were evaluated using XPS. CA 125 antibody conjugation with CuPy was confirmed using UV–visible absorbance spectroscopy, fluorescence spectroscopy, and FTIR spectroscopy. The antibody binding resulted in the fluorescence shifts towards higher wavelengths with an increase in the emission intensity compared with CuPy. Zeta potential measurements also confirmed the binding of the CA 125 antibody to the sensor. Different concentrations of CA 125 antigen resulted in the quenching of fluorescence. This change in the fluorescence intensity was used for the detection of CA 125. Conclusions: A copper-based optical material was developed using low-temperature plasma, and it was found to be effective for the detection of CA 125 ovarian cancer marker. Full article

Ovarian cancer remains a leading cause of gynecological cancer-related mortality. Although the standard therapy is usually effective at first, the development of multidrug resistance (MDR) significantly limits the efficacy of the treatment. Topotecan (TOP) is a drug commonly used in second-line therapy. However, the cancer cells eventually become immune to its cytotoxic effect, as they start to produce ATP-binding cassette (ABC) transporters, proteins facilitating drug removal. Breast cancer resistance protein (BCRP) is one such protein, and TOP is its known substrate. Vismodegib, a Sonic Hedgehog pathway (Shh) inhibitor, has demonstrated potential anticancer activity in various malignancies. This study aims to evaluate the effects of Vismodegib treatment on both topotecan-sensitive and -resistant ovarian cancer cell lines, cultured in two-dimensional (2D) and three-dimensional (3D) conditions, as well as the potential of Vismodegib treatment to reverse the acquired drug resistance. Our results suggest that Vismodegib re-sensitizes TOP-resistant cells in both 2D and 3D models. However, further research is needed to evaluate its usefulness in ovarian cancer treatment. Full article

Background: Paraneoplastic neurological syndromes (PNSs) are rare immune-mediated disorders associated with malignancies and may precede the diagnosis of the underlying tumor. Ovarian cancers, including both epithelial tumors and teratomas, have been associated with a spectrum of antibody-mediated neurological syndromes, although their clinical implications remain poorly defined. Objective: To describe three cases of PNS associated with ovarian malignancies and to provide a narrative review of the literature focusing on their diagnostic and clinical implications. Methods: We report three patients managed at our institution who developed paraneoplastic neurological syndromes in association with ovarian cancer. In parallel, a narrative review of the literature was conducted through PubMed and Google Scholar to identify studies published between 2020 and 2025 reporting PNS in ovarian malignancies. Relevant studies were selected and analyzed qualitatively, with emphasis on timing of onset, clinical presentation, antibody profiles, treatment strategies, and outcomes. Results: Eighteen studies were included, the majority of which were case reports. In most cases, neurological symptoms preceded the diagnosis of ovarian cancer, highlighting their potential role as an early clinical indicator of malignancy. Cerebellar degeneration was the most frequent presentation, often associated with anti-Yo antibodies, while encephalitis was more commonly linked to anti-NMDAR antibodies. Our clinical cases illustrate the heterogeneity of presentation and the complexity of diagnosis and management, requiring a multidisciplinary approach. Across studies, outcomes were variable, with partial improvement or stabilization observed in most cases following oncologic and immunomodulatory treatment. Conclusions: Paraneoplastic neurological syndromes may represent an early clinical clue to ovarian malignancy. Increased awareness among clinicians is essential to prompt appropriate diagnostic evaluation and timely oncologic management. Further research is needed to clarify the role of onconeural antibodies in early detection and disease monitoring. Full article

Ovarian cancer, particularly high-grade serous ovarian cancer (HGSOC), remains one of the most lethal gynecological malignancies due to late diagnosis and the development of chemoresistance. The tumor microenvironment (TME) plays an important role in disease progression, with chemokines influencing cell recruitment, angiogenesis, metastasis, and immune modification. This review synthesizes current evidence on key chemokine axes in ovarian cancer, highlighting their dual roles as prognostic biomarkers and therapeutic targets. The most important axes include CXCL12/CXCR4 (which drives tumor proliferation, angiogenesis and chemoresistance via epithelial–mesenchymal transition), CCL2/CCR2 (promoting immunosuppressive tumor-associated macrophages and resistance), and CCL5/CCR5 (enhancing pro-oncogenic signaling and Treg/MDSC infiltration). Pro-angiogenic ELR+CXC chemokines like CXCL8 induce vascularization and inflammation. On the contrary, effector chemokines (CXCL9/10/11/13) correlate with “hot” immune subtypes and improved survival in several studies. High expression of immunosuppressive chemokines predicts poorer prognosis and therapy resistance, while immune-attracting profiles associate with better outcomes and chemotherapy responsiveness. Therapeutically, inhibitors like plerixafor (CXCR4), PF-04136309 (CCR2), and maraviroc (CCR5) show preclinical promise, synergizing with chemotherapy, anti-VEGF, and checkpoint inhibitors. Chemokines also represent actionable molecular targets to overcome ovarian cancer’s “cold” immune phenotype. Future research should validate multi-chemokine signatures for patient stratification and advanced clinical trials toward personalized therapies. Full article