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Abstract: 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.
Keywords: body fluids, chronic inflammation, HIF-1a, high-grade serous ovarian carcinoma, neoadjuvant chemotherapy, tumor tissue
Published in DiRROS: 26.03.2026; Views: 142; Downloads: 81
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Abstract: 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.
Keywords: induction chemotherapy, chemoradiotherapy, arynx preservation
Published in DiRROS: 16.01.2026; Views: 299; Downloads: 295
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Abstract: 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.
Keywords: glioblastoma, mitochondria, metabolism, chemotherapy, stem cells
Published in DiRROS: 26.11.2025; Views: 349; Downloads: 248
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Abstract: 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.
Keywords: ovarian cancer, tumour marker, neoadjuvant chemotherapy, CA-125
Published in DiRROS: 22.07.2024; Views: 1113; Downloads: 384
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Abstract: Background. Glioblastoma (GBM) is the most common and the most malignant glioma subtype. Among numerous genetic alterations, miRNAs contribute to pathogenesis of GBM and it is suggested that also to GBM recurrence and resistance to therapy. Based on publications, we have selected 11 miRNAs and analyzed their expression in GBM. We hypothesized that selected miRNAs are differentially expressed and involved in primary as well as in recurrent GBM, that show significant expressional differences when different treatment options are in question, and that are related to certain patients and tumor characteristics. Patients and methods. Paraffin embedded tissues, obtained from primary and corresponding recurrent tumor from 83 patients with primary GBM were used. Eleven miRNAs ( miR-7, miR-9, miR-15b, miR-21, miR-26b, miR-124a, miR-199a, let-7a, let-7b, let-7d, and let-7f ) were selected for qPCR expression analysis. For patients who received temozolamide (TMZ) as chemotherapeutic drug, O6-methylguanine-DNA methyltransferase (MGMT) methylation status was defined using the methyl-specific PCR. Results. There was a significant change in expression of miR-7, miR-9, miR-21, miR-26b, mirR-124a, miR-199a and let- 7f in recurrent tumor compared to the primary. In recurrent tumor, miR-15b, let-7d and let-7f significantly changed comparing both treatment options. We also observed difference in progression free survival between patients that received radiotherapy and patients that received radiotherapy and chemotherapy, and longer survival for patients who received chemotherapy after second surgery compared to not treated patients. miR-26b showed correlation to progression free survival and let-7f to overall survival. We did not find any expression difference between the tumors with and without methylated MGMT. Conclusions. Our data suggest that analyzed miRNAs may not only contribute to pathogenesis of primary GBM, but also to tumor progression and its recurrence. Moreover, expression of certain miRNAs appears to be therapy- dependent and as such they might serve as additional biomarker for recurrence prediction and potentially predict a therapy-resistance.
Keywords: glioblastoma, radiotherapy, chemotherapy
Published in DiRROS: 02.07.2024; Views: 1188; Downloads: 673
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