Immunotherapy, particularly approaches that combine tumor-specific vaccines with immune checkpoint modulation, represents a promising strategy for overcoming tumor immune evasion. While most mRNA-based cancer vaccines focus solely on antigen delivery, there is a need for platforms that simultaneously enhance antigen presentation and modulate the tumor microenvironment to increase therapeutic efficacy. This study presents a novel dual-nanolipid exosome (NLE) platform that simultaneously delivers MUC1 mRNA and CTLA-4-targeted siRNA in a single system. These endogenous lipid-based nanoparticles are structurally designed to mimic exosomes and are modified with mannose to enable selective targeting to dendritic cells (DCs) via mannose receptors. The platform was evaluated both in vitro and in vivo in terms of mRNA encapsulation efficiency, nanoparticle stability, and uptake by DCs. The co-delivery platform significantly enhanced antitumor immune responses compared to monotherapies. Flow cytometry revealed a notable increase in tumor-infiltrating CD8⁺ T cells (p < 0.01), and ELISPOT assays showed elevated IFN-γ production upon MUC1-specific stimulation. In vivo CTL assays demonstrated enhanced MUC1-specific cytotoxicity. Combined therapy resulted in immune response enhancement compared to vaccine or CTLA-4 siRNA alone. The NLE platform exhibited favorable biodistribution and low systemic toxicity. By combining targeted delivery of dendritic cells, immune checkpoint gene silencing, and efficient antigen expression in a biomimetic nanoparticle system, this study represents a significant advance over current immunotherapy strategies. The NLE platform shows strong potential as a modular and safe approach for RNA-based cancer immunotherapy.

Background/Objectives: Glioblastoma is a highly aggressive brain tumor with limited treatment options and poor prognosis. Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in glioblastoma progression, making it a promising therapeutic target. However, effective delivery of STAT3-silencing agents across the blood–brain barrier remains a significant challenge. This study evaluates the efficacy of Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment in reducing glioblastoma tumor growth by facilitating efficient small interfering RNA delivery and inhibiting STAT3 expression. Methods: A novel exosome-based drug delivery system was developed using NLP-EXOSOME COMPLEX nanoparticles loaded with STAT3-silencer siRNA. The therapeutic efficacy was assessed in vitro using human glioblastoma cell lines and in vivo using a glioblastoma mouse model. Tumor progression, STAT3 expression levels, and survival rates were analyzed. Results: The results demonstrated that Lipid Nanoparticles-EXOSOME COMPLEX effectively transported STAT3-silencer siRNA into glioblastoma cells, leading to significant STAT3 downregulation. This resulted in reduced tumor proliferation, increased apoptosis, and extended survival in vivo. The combination of lipid nanoparticles and exosomes provided a stable and efficient delivery mechanism with improved uptake and therapeutic efficacy. Conclusion: Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment offers a promising approach for targeted glioblastoma therapy by overcoming the blood–brain barrier limitations and enhancing STAT3 inhibition. Further research is necessary to optimize long-term efficacy, assess potential immune responses, and explore combinatory therapeutic strategies for improved patient outcomes.

Objective: This study primarily aimed to identify baseline clinical and laboratory predictors of hematologic toxicity during first-line platinum-based chemotherapy in BRCA-mutated ovarian cancer patients. Secondary objectives included describing toxicity patterns and evaluating the association between hematologic toxicity and survival outcomes. Methods: This retrospective study included 64 patients with BRCA-mutated ovarian cancer who received platinum-taxane-based chemotherapy and were followed up at the İstanbul University Institute of Oncology between January 2009 and September 2024. Hematological toxicity was assessed using complete blood count before each chemotherapy cycle. Clinical data, factors associated with toxicity, and survival outcomes were compared between groups. Results: Hematologic toxicity occurred in 29.7% of the patients. The baseline leukocyte, neutrophil, and platelet counts were significantly lower in patients with toxicity. Additionally, patients with toxicities had more comorbidities at the baseline. Although the rate of dose modification was higher in the hematologic toxicity group, there were no significant differences between the groups in terms of treatment response or survival outcomes. Conclusion: Although hematologic toxicity was associated with more frequent dose modifications, no statistically significant differences in survival outcomes were observed between the groups. Baseline hematologic values and comorbidities should be considered in individualized planning of chemotherapy. Large-scale prospective studies are warranted to enhance the understanding of this topic. Cite this article as: Çokgezer S, Senkal M, Safaraliyeva A, Bozbey HU, Taştekin D. Hematologic toxicity during first-line platinum-based chemotherapy in BRCA-mutated ovarian cancer: predictors and survival impact. Cerrahpaşa Med J 2026; 50, 0033, doi: 10.5152/cjm.2026.26033.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies for which there are few effective biomarkers for diagnosis, prognosis, and treatment monitoring. Given the paucity of data in the literature, this study aimed to evaluate the biomarker potential of selected miRNAs (miR-222-3p, miR-3154, miR-3945, miR-4534, and miR-4742) and their protein targets in the context of PDAC. Methods: The expression levels of miRNA candidates were quantified by real-time quantitative PCR in lymphocyte samples from 46 PDAC patients and 50 healthy controls. In silico analyses were performed to identify potential target genes and proteins. ELISA was used to measure protein expression in both groups. Statistical analyses included ROC curve analysis, linear regression, and correlation analyses. In addition, correlations between miRNA/protein expression and clinicopathologic characteristics, including survival, were investigated. Results: miR-222-3p and miR-3154 were significantly downregulated in PDAC patients compared to controls (p < 0.001). Among the dual miRNA combinations, miR-222-3p and miR-4534 showed the highest discriminatory power (AUC = 0.629, p = 0.022). The miR-222-3p expression was significantly increased in patients with a history of alcohol consumption (p = 0.02). Significant correlations were observed between miR-3154 expression and T-stage (p = 0.01) and between perineural invasion and miR-222-3p levels (p = 0.02). Survival analysis showed that high miR-3945 expression was significantly associated with shorter overall survival (p = 0.001). Elevated levels of ESR1, HCFC1, and EPC1 were significantly associated with lymphatic invasion (p < 0.05), while high KCNA1 expression correlated with shorter survival (p = 0.006), indicating its potential as a negative prognostic biomarker. Linear regression analysis revealed a significant positive correlation between miR-3945 and KCNA1 expression (β = 0.259, p = 0.038), indicating a possible regulatory interaction. A borderline correlation was also found between miR-4742 and EPC1 expression (p = 0.055). Conclusions: This study identifies several miRNAs and associated proteins with diagnostic and prognostic significance in PDAC. The results emphasize the clinical relevance of integrating multi-layered analyses of miRNA–protein interactions. The observed associations highlight the role of these molecular markers in tumor progression and patient survival and offer promising opportunities for future research and clinical application in precision oncology.