Ovarian cancer remains the most lethal gynecologic malignancy, with acquired platinum resistance accounting for the majority of treatment failures. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a metabolic vulnerability that therapy-resistant cancers cannot fully evade. This review examines the relationship between ferroptosis and chemotherapy resistance in high-grade serous ovarian cancer (HGSOC), analyzing the GPX4 antioxidant axis, polyunsaturated fatty acid biosynthesis, and iron homeostasis. We highlight recent discoveries including BRCA1-dependent ubiquitination of GPX4 and its implications for PARP inhibitor synthetic lethality, NR1D2-mediated transcriptional repression of FSP1, and stromal protection conferred by cancer-associated fibroblasts. The unique features of ovarian cancer-iron-abundant ascites, the lipid-rich omental niche, and prevalent BRCA mutations-present distinctive therapeutic opportunities. We introduce the novel concepts of a "ferroptosis compensatory threshold" requiring concurrent multi-node inhibition, and the need for personalized therapeutic design based on tumor ferroptosis defense profiling. We also address challenges confronting clinical translation: on-target toxicities, resistance mechanisms, spatial heterogeneity in ferroptosis susceptibility, and the need for validated predictive biomarkers. By synthesizing these cutting-edge findings, we provide a framework that integrates cancer genetics, microenvironment metabolism, and immunology, distinguishing this review from previous summaries and highlighting actionable vulnerabilities for overcoming chemoresistance in ovarian cancer.

Diminished lymphocyte infiltration and activation in ovarian cancer are attributable to the malignancy and irresponsiveness to immunotherapy. We show here that treatment of a murine model of ovarian cancer with recombinant tumor necrosis factor superfamily-15 (TNFSF15) results in a marked inhibition of peritoneal dissemination of the cancer cells and a substantial reduction of ascites. The treatment leads to normalization of the tumor vasculature judged by enhanced coverage of the neo-blood vessels with PDGFβ[+] pericytes and diminished levels of the hypoxia-responsive cancer stem cell marker CD133. Additionally, the treatment gives rise to accumulation of Lyve-1[+] lymphatic endothelial cells and PNAd[+] high endothelial venules (HEV) in the tumors, consistent with the formation of tertiary lymphoid structures (TLS). Moreover, the treatment results in facilitated tumor infiltration of T cells, B cells, macrophages, and dendritic cells, the latter exhibit upregulated expression of TLS-associated cytokines and chemokines, including Lt-α, Lt-β, IFN-β, TNF-α, CCL19, CCL21, CXCL13, and CXCL10. Furthermore, there is an enhanced responsiveness in TNFSF15-treated tumors toward PD-1 blockade treatment. These findings suggest that TNFSF15 is capable of facilitating vascular normalization and TLS formation, and thus promoting a reinstitution of the immune microenvironment in ovarian cancer.

Canine large-cell alimentary lymphoma (LCAL) is an aggressive malignancy with limited effective treatment options and a poor prognosis. In a preliminary drug screening study using three canine LCAL cell lines (CLC, Ema, and Nody-1), the taxane cabazitaxel (CBZ) was identified as a promising candidate drug. This study aimed to evaluate the antitumour effects of CBZ in vitro and in vivo and determine its potential as a novel therapeutic candidate for canine LCAL. Cell viability, tubulin polymerisation, cell cycle distribution, and apoptosis were assessed in CLC, Ema, and Nody-1 cells following treatment with CBZ or vehicle control. In addition, the effect of CBZ was evaluated in a xenotransplantation mouse model established using CLC cells. CBZ reduced cell viability across all cell lines in a dose-dependent manner, with sub-nanomolar half-maximal inhibitory concentrations. A tubulin polymerisation assay demonstrated that CBZ increased polymerised tubulin levels, indicating microtubule stabilisation. CBZ treatment induced G2/M cell cycle arrest and significantly increased apoptotic cell populations, accompanied by decreased procaspase-3 levels and increased cleaved caspase-3 expression. In vivo, CBZ treatment reduced ascites accumulation and significantly prolonged survival relative to the vehicle control. These findings suggest that CBZ induces G2/M cell cycle arrest and caspase-dependent apoptosis through tubulin stabilisation and suppresses tumour progression in vivo. CBZ represents a promising therapeutic candidate for canine LCAL.

Non-Hodgkin's lymphoma (NHL) is a common lymphatic system malignancy that typically presents with painless lymphadenopathy. Acute symptoms resulting from extranodal involvement are rare and may lead to diagnostic challenges in the emergency setting. We report a case of NHL in a 39-year-old male patient who presented to the emergency department with abdominal distension, oliguria, and acute dyspnea. Imaging revealed a large retroperitoneal mass with bilateral pleural effusions and ascites. The patient underwent symptomatic treatment and was admitted to the ICU. Histopathological examination of the mass confirmed the diagnosis of non-Hodgkin's lymphoma. This case highlights the importance of considering lymphoma in the differential diagnosis of retroperitoneal masses with acute systemic manifestations and emphasizes a cautious approach to surgical intervention in the emergency setting.

Cobalt-zinc ferrite nanoparticles (Co1-xZnxFe2O4; x = 0, 0.35) were synthesized using a flash-combustion method and characterized by FTIR and SEM to evaluate their structural and surface properties. This study investigated the in vitro and in vivo antitumor efficacy of cobalt ferrite nanoparticles (CF NPs). In vitro, human breast cancer cells (MCF-7) were used to determine cytotoxicity (IC50), apoptosis, and cell cycle effects. The IC50 of CF NPs was 144 µg/mL. Treatment with 1/10 IC50 increased necrotic, early apoptotic, and late apoptotic cell populations to 7.2%, 9.5%, and 12.6%, respectively. CF NPs arrested the cell cycle at sub-G1 and G2/M phases, while IC50 of cisplatin was 11.25 µg/mL. Treatment with1/10 IC50 arrested the cell cycle at S and G2/M phases. For in vivo analysis, forty female albino mice (CD-1) were divided into four groups. Tumor induction was performed using Ehrlich ascites carcinoma (EAC) cells (1 × 10[6]/mouse). After 24 h, mice received either cisplatin (2 mg/kg) or CF NPs (150 mg/kg; 1/10 LD50). After 14 days, CF NP treatment significantly reduced body weight gain, tumor volume (44%), tumor cell count (28%), and viable tumor cells (30%). Additionally, CF NPs improved hematological parameters, liver and kidney function, and restored normal histological architecture of hepatic and renal tissues. CF NPs exhibit significant antitumor activity both in vitro and in vivo by inducing apoptosis, suppressing tumor growth, and improving biochemical and histopathological parameters, supporting their potential as a promising adjunct in cancer nanotherapy.

Background and Objectives: Malignant ascites reflects the tumor microenvironment and provides valuable insights into peritoneal metastasis. This study aimed to assess soluble immune system-related molecules in the ascites fluid of advanced gastrointestinal cancer patients with peritoneal carcinomatosis and to explore potential therapeutic opportunities. Methods: This multicenter prospective cohort study included 48 patients with gastrointestinal adenocarcinoma (17 colorectal, 16 gastric, and 15 pancreatic) with malignant ascites and 15 patients for comparison who required benign ascites drainage for advanced heart failure. Blood samples for routine parameters and ascites fluid for cytokine and soluble immune checkpoint analysis were collected. Parameters were compared between cancer patients and the comparison group, across cancer subgroups, and in correlation with survival. Results: The mean age of participants was 60.2 ± 14.9 years, with a female-to-male ratio of 11:20. The median survival of cancer patients was 84.0 days. Compared with heart failure-associated transudative ascites, malignant ascites demonstrated higher levels of TNF-α, IL-6, IL-10, IL-12p70, IL-18, IL-23, s4-1BB, and TGF-β1, while albumin levels were lower. Significant intergroup differences were observed in TNF-α, IL-6, IL-8, IL-10, IL-12p70, IL-23, 4-1BB, TGF-β1, and PD-L1 levels. In exploratory multivariable analysis, IL-10 and soluble 4-1BB emerged as potential predictors of shorter survival, although these findings require validation in larger cohorts. Survival was negatively correlated with PD-L1, TNF-α, IL-6, and IL-10 in colorectal cancer; 4-1BB, TGF-β1, IL-8, and IL-10 in gastric cancer; and TGF-β1, IL-6, and IL-10 in pancreatic cancer. Conclusions: These exploratory findings indicate that the immunosuppressive milieu in malignant ascites in gastrointestinal cancers may be mediated by cancer subtype-specific pathways, warranting further mechanistic and translational investigation.

Ascites, a hallmark of advanced ovarian cancer, severely impairs patient quality of life and contributes to therapeutic resistance. Current management strategies remain primarily palliative, highlighting the urgent need to elucidate the underlying mechanisms. Although TREM2[+] macrophages are enriched in malignant ascites, the role of soluble TREM2 (sTREM2) in regulating vascular function and ascites pathogenesis remains poorly understood. Here, we show that sTREM2 levels are elevated in malignant ascites and positively correlate with ascites volume. Using a combination of in vitro, in vivo, and ex vivo models, we demonstrate that sTREM2 promotes vascular permeability and drives ascites formation. Mechanistically, sTREM2 binds to nucleolin (NCL) on endothelial cells and activates the AKT/eNOS signaling pathway, which leads to VE-cadherin phosphorylation and ultimately vascular leakage. sTREM2-induced hyperpermeability was abolished by NCL knockdown or eNOS inhibition. Importantly, administration of a neutralizing antibody against sTREM2 significantly reduced ascites formation and tumor burden in mouse models. Our study identifies the sTREM2-NCL-AKT-eNOS axis as a critical driver of vascular leakage and malignant ascites in ovarian cancer, highlighting it as a promising therapeutic target.

Combination therapy has emerged as a standard strategy for enhancing the efficacy of anticancer treatments. The purpose of our study was to assess the melatonin-selenium nanoparticles' anticancer potential (MSeNPs) in a murine model of Ehrlich ascites carcinoma (EAC). Assessments included cell viability, hematological parameters, oxidative stress markers, apoptosis, cell cycle dynamics, and pro-inflammatory cytokines. Our findings demonstrate that MSeNPs inhibit tumor growth and enhance antioxidant defenses. MSeNPs significantly reduce IL-6 levels, alleviating EAC-associated inflammation. Furthermore, MSeNPs induced apoptosis through caspase-3 activation and Ki-67 downregulation, resulting in decreased cell proliferation and significant G0/G1 cell cycle arrest, accompanied by marked suppression of the S phase. In conclusion, these results highlight the synergistic therapeutic advantage of MSeNPs, indicating greater efficacy than monotherapies with melatonin, selenium, or selenium nanoparticles alone. MSeNPs hold promise as a potent, multi-targeted agent for future cancer therapies.