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Povzetek: o improve the treatment outcome and survival of patients with advanced high-grade serous carcinoma (HGSC), prognostic biomarkers for assessing the feasibility of complete (R0) or optimal (R1) primary cytoreductive surgery are needed. Additionally, biomarkers for predicting the response to neoadjuvant chemotherapy (NACT) in patients with primary inoperable disease could help stratify patients for tailored therapy and improve personalised approach. Such promising biomarkers are extracellular vesicles (EVs), which are present in ascites and plasma and are available for minimally invasive liquid biopsy. EV concentration and EV molecular profile have been at the forefront of research in the field of biomarkers for many years now, but recent studies have highlighted the importance of EV size distribution. Our study aimed to evaluate the potential of the EV concentration and size distribution in pretreatment ascites and plasma samples from patients with advanced HGSC as prognostic biomarkers. In our prospective cohort study, nanoparticle tracking analysis (NTA) was used to determine EV characteristics in paired pretreatment ascites and plasma samples from 37 patients with advanced HGSC. Patients were treated with primary cytoreductive surgery followed by adjuvant chemotherapy (ACT) (N = 15) or NACT followed by interval debulking surgery (IDS) when optimal cytoreduction was not feasible (N = 22). The correlations of the EV concentration and size distribution in ascites and plasma with treatment outcome, progression-free survival (PFS) and overall survival (OS) were analysed. We found a significant correlation between the EV size distribution in ascites and residual disease after primary cytoreductive surgery. Larger EVs in ascites correlated with worse resection success after primary cytoreductive surgery. A significant correlation between the D10 value of EVs in plasma and the chemotherapy response score (CRS) after NACT was observed. A smaller D10 value of plasma EVs was correlated with a better chemotherapy response. Receiver operating characteristic (ROC) curve analysis revealed excellent performance for D10 value in ascites for the prediction of suboptimal (R2) resection at primary debulking surgery and excellent performance for D10 value in plasma for the prediction of complete or near-complete chemotherapy response score (CRS 3) at interval debulking surgery. There was a significant correlation between the mean diameter, D90 value and proportion of medium/large (> 200 nm) EVs in ascites and those in plasma. On the other hand, there was no correlation of the EV concentration or D10 and D50 values between the ascites fluid and plasma samples. Our results indicate that the EV size distribution in ascites has the potential to predict resection success after primary cytoreductive surgery and that the EV size distribution of the smallest EVs in plasma might help predict the chemotherapy response of patients treated with NACT. In the future, molecular analyses of size-dependent EV cargo could provide more insight into their biological functions and potential as predictive biomarkers.
Ključne besede: biomarkers, chemotherapy responce, extracellular vesicles, high-grade serous carcinoma, nanoparticle tracking analysis, resection success, treatment outcome
Objavljeno v DiRROS: 20.04.2026; Ogledov: 310; Prenosov: 290
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Povzetek: High-grade serous ovarian carcinoma (HGSOC) is marked by late diagnosis and chemoresistance, partly driven by chronic inflammation and hypoxia in the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1a) is a key regulator of these processes; however, its spatial distribution, interaction with inflammation, and effect on chemotherapy response in HGSOC remain unclear. This retrospective study included 28 advanced HGSOC patients treated with neoadjuvant chemotherapy (NACT). Samples were collected at primary surgery (PS) (ovarian and peritoneal tissue, plasma, ascites) and post-NACT at interval debulking surgery (IDS) (omentum, peritoneal tissue, plasma). HIF-1a mRNA expression varied by site, with higher levels in omental and peritoneal tissues compared to ovarian tissue. Plasma and ascites concentrations were significantly correlated, although the mean ascites concentration was lower. Elevated HIF-1a concentration in ascites and plasma at baseline correlated with ESR (erythrocyte sedimentation rate) >30 mm/h, which was also correlated with BRCA mutation status. No correlation was found between HIF-1a and CRP (C-reactive protein) levels. Higher HIF-1a concentrations in ascites and plasma were linked to poor chemotherapy response (CRS1) at IDS. No significant changes in plasma HIF-1a, ESR, or peritoneal HIF-1a mRNA expression were observed before and after chemotherapy. Increased peritoneal HIF-1a at baseline showed a trend toward shorter progression-free survival. These findings suggest that HIF-1a may reflect hypoxia-inflammation crosstalk associated with chemoresistance and progression in HGSOC. The hypoxic-inflammatory microenvironment appears to persist despite chemotherapy and could contribute to ongoing disease activity. However, these observations require validation in independent cohorts before any prognostic or predictive implications can be considered.
Ključne besede: body fluids, chronic inflammation, HIF-1a, high-grade serous ovarian carcinoma, neoadjuvant chemotherapy, tumor tissue
Objavljeno v DiRROS: 26.03.2026; Ogledov: 320; Prenosov: 229
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Povzetek: To test the hypothesis that clinical tumor response after a single cycle of induction chemotherapy (ICT) can reliably differentiate between chemo-/radiosensitive and resistant tumors in the larynx preservation setting. Patients and methods Treatment consisted of docetaxel/cisplatin/5-fluorouracil (TPF) ICT followed by concurrent chemoradiotherapy (cCRT) with weekly cisplatin. The response of the primary tumor was assessed by transnasal endoscopy after the first ICT cycle. Results 37/39 (95%) patients with laryngeal (46%) or hypopharyngeal (54%) carcinoma responded to one cycle of ICT, and two patients were referred for salvage surgery. Laryngectomy-free survival at 2 and 5 years was 87% and 75%, respectively. The corresponding rates for locoregional control (and also for disease-free survival) were 79% and 70% and for overall survival 92% and 82%. Conclusions Clinical assessment of tumor response to one cycle of TPF ICT serves as a valid and easy-to-use predictor of tumor sensitivity to platinum-based cCRT.
Ključne besede: induction chemotherapy, chemoradiotherapy, arynx preservation
Objavljeno v DiRROS: 16.01.2026; Ogledov: 524; Prenosov: 666
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Povzetek: Background[:] Glioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells. Materials and methods[:] Patient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis. Results[:] We found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae are indicating increased biogenesis and mitochondrial fusion and corresponds to a more oxidative phosphorylation (OXPHOS)-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced ultrastructural mitochondrial damage in differentiated GBM cells. Conclusions[:] We demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.
Ključne besede: glioblastoma, mitochondria, metabolism, chemotherapy, stem cells
Objavljeno v DiRROS: 26.11.2025; Ogledov: 555; Prenosov: 473
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Povzetek: Background. Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125. Patients and methods. At the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results. The median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4%9.5) and 18 months (95% CI 12.5%23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6%29.5) and 46 months (95% CI 32.9%62.1), respectively. Conclusions. Preoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.
Ključne besede: ovarian cancer, tumour marker, neoadjuvant chemotherapy, CA-125
Objavljeno v DiRROS: 22.07.2024; Ogledov: 1355; Prenosov: 450
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