351. In vitro evaluation of electrochemotherapy combined with sotorasib in pancreatic carcinoma cell lines harboring distinct kras mutationsTanja Jesenko, Maša Omerzel, Tina Živič, Gregor Serša, Maja Čemažar, 2025, original scientific article Abstract: Pancreatic cancer is among the deadliest malignancies, with limited treatment options and poor prognosis. Novel strategies are therefore urgently needed. Sotorasib, a KRAS G12C-specific inhibitor, offers targeted treatment for a small subset of patients with this mutation. Electrochemotherapy (ECT), which enhances the cytotoxicity of chemotherapeutic agents through electroporation-induced membrane permeabilization, has shown promise in various tumor types, including deep-seated malignancies such as pancreatic cancer. Combining ECT with sotorasib may potentiate antitumor effects in KRAS G12C-mutated pancreatic cancer; however, preclinical data on such combinations are lacking. This proof-of-concept study evaluated the cytotoxic effects of ECT using bleomycin (BLM) or cisplatin (CDDP) in combination with sotorasib in KRAS G12C-mutated MIA PaCa-2 and KRAS G12D-mutated PANC-1 pancreatic cancer cell lines. ECT alone significantly reduced cell viability, particularly in MIA PaCa-2 cells, where electric pulses induced approximately 75% cell death. Combining ECT with sotorasib resulted in an additive effect on KRAS G12C-mutated MIA PaCa-2 cells, though no synergy was observed, likely due to the high intrinsic sensitivity to electric pulses. These results support the potential of combining physical and molecular therapies in a subset of pancreatic cancer patients and lay the groundwork for further in vivo studies to optimize treatment parameters and explore clinical translatability.
Keywords: bleomycin, cisplatin, electrochemotherapy, pancreatic cancer
Published in DiRROS: 26.11.2025; Views: 91; Downloads: 43
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353. Sequencing of chemotherapy in total neoadjuvant treatment for rectal cancer does not predict radiation-induced lymphopeniaMiha Oražem, Vaneja Velenik, Alojz Ihan, 2025, original scientific article Abstract: Radiation-induced lymphopenia (RIL) is associated with an increased risk of death in solid tumors, including rectal cancer. The aim of this study was to determine whether the sequencing of chemotherapy in total neoadjuvant treatment (TNT) for rectal cancer predicts the development of RIL. Patients and methods We analyzed acute hematologic toxicity data from 53 patients who underwent TNT for locally or locoregionally advanced rectal cancer between July 2022 and April 2023. Twenty-eight patients received induction chemotherapy with capecitabine and oxaliplatin [CAPOX], and 25 received consolidation chemotherapy (6 cycles of CAPOX in both groups). The chemoradiation protocol consisted of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost Radiotherapy (VMAT-SIB RT) up to 48.4 Gy in 22 fractions, concomitantly with capecitabine twice a day (lat. bis in die, BID). The Mann-Whitney U test was performed to compare RIL between the two patient groups. Pelvic bone marrow was contoured as a non-limiting organ-at-risk to assess the received dose, and binary logistic regression was used to determine whether RIL depends on V5Gy~V42Gy or the planning target volume (PTV) size. Results Thirty-four patients (64.2%) developed RIL of any grade, which was not significantly associated with either the induction or consolidation chemotherapy TNT regimen (Wald = 3.159, p = 0.076). No significant differences were found in neutrophil counts or the neutrophil-to-lymphocyte ratio. In the logistic regression model predicting the likelihood of RIL, two variables were statistically significant: V10Gy (Wald = 4.366, p = 0.037) and V30Gy (Wald = 6.084, p = 0.014). These results indicate that V10Gy< 71% and V30Gy< 26.6% may reduce the likelihood of developing RIL. Conclusions In our study, the sequencing of chemotherapy in TNT for rectal cancer did not predict the development of RIL. However, the incidence of RIL may be reduced by applying RT dosimetric constraints to the pelvic bone marrow.
Keywords: radiation-induced lymphopenia, rectal cancer, total neoadjuvant treatment
Published in DiRROS: 26.11.2025; Views: 136; Downloads: 42
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354. Gender impact on quality of life in colorectal cancer survivorsAleksandra Grbič, Majda Čaušević, Sara Brodarič, Mojca Birk, Irena Oblak, 2025, original scientific article Abstract: The aim of the study was to evaluate gender-specific differences in the quality of life (QoL) and late effects among colorectal cancer patients during the first two years after treatment, to inform and improve long-term follow-up care and clinical management strategies. Patients and methods A total of 239 colorectal cancer patients were included, 56% males and 44% females, mostly in the age range 60–69 years. They were treated at the Institute of Oncology Ljubljana, during the time period from 1st September 2023 to 1st May 2024. In addition to demographic data, we included clinical data on disease and outcomes collected using the standardized quality of life questionnaires of European Organization for Research and Treatment of Cancer (EORTC) named EORTC QLQ-30 and EORTC QLQ-CR29 for colorectal cancer, respectively. Results Females were more likely to experience emotional problems (p = 0.002), higher levels of fatigue (p < 0.001), insomnia (p = 0.015), nausea and vomiting (p = 0.007), which may also be associated with poorer appetite in females. Males reported better body image than female (p = 0.047), lower levels of anxiety (p = 0.029), less frequently reported perceived weight loss or gain (p = 0.010). Male reported more stool frequency (p = 0.045), and also had more sever dysuria compared to female (p = 0.008). Conclusions The results provide the opportunity to improve the clinical management of long-term follow-up and care planning, taking into consideration the gender-specific needs of colorectal cancer survivors.
Keywords: quality of life, late effects, colorectal cancer
Published in DiRROS: 26.11.2025; Views: 142; Downloads: 39
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355. PET/CT and MR improve interobserver agreement in primary tumor determination for radiotherapy in esophageal squamous cell cancerAjra Šečerov Ermenc, Primož Peterlin, Vaneja Velenik, Ana Jeromen, Jasna But-Hadžić, Franc Anderluh, Barbara Šegedin, 2025, original scientific article Abstract: The aim of the study was to evaluate interobserver variability in the determination of the primary tumor for radiotherapy treatment planning in esophageal squamous cell carcinoma (ESCC). Methods: Sixteen patients with locally advanced ESCC were included in the analysis. In all patients positron emission tomography with computed tomography (PETC/CT) and magnetic resonance (MR) scans for radiotherapy planning were performed. Five experienced radiation oncologists delineated the primary tumor based on CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR. Mean tumor volumes were calculated for each patient and imaging modality. The generalized conformity index (CIgen) was calculated to assess agreement in tumor determination. Results: The mean tumor volumes and CIgen for CT alone, MR alone, PET/CT, CT with fused MR and PET/CT with fused MR were 33.1 cm3, 30.2 cm3, 38.1 cm3, 31.9 cm3, 36.2 cm3 and 0.59, 0.64, 0.66, 0.63, 0.71, respectively. CIgen was significantly higher using PET/CT with fused MR compared to CT (p < 0.001) and PET/CT (p = 0.002) and using PET/CT compared to CT (alone) (p = 0.003). Conclusions: Our study showed higher agreement in primary tumor determination in ESCC using PET/CT compared to CT alone. Higher agreement was also found using PET/CT with fused MR compared to CT alone and PET/CT.
Keywords: magnetic resonance, positron emission tomography, squamous cell carcinoma, primary tumor
Published in DiRROS: 26.11.2025; Views: 113; Downloads: 43
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356. Are there clinically relevant prognostic factors in diffuse large B-cell lymphoma beyond International Prognostic IndexMilica Miljković, Vita Šetrajčič Dragoš, Gorana Gašljević, Srdjan Novaković, Lučka Boltežar, Barbara Jezeršek Novaković, 2025, original scientific article Abstract: Diffuse large B-cell lymphoma (DLBCL) has variable prognosis, with only 50 to 60% of patients cured by standard first line treatment. Identifying patients unlikely to benefit from standard first line therapy is therefore crucial. Schmitz’s study identified four molecular subtypes of DLBCL with differing prognoses: MCD, BN2, N1, and EZB, with BN2 and EZB showing more favorable outcomes. This study aimed to evaluate the effectiveness of the Archer FusionPlex Lymphoma Assay in identifying the newly defined genetic subtypes of DLBCL, while also exploring the association between immunohistochemical (IHC) and next-generation sequencing (NGS) methods for classifying the cell of origin (COO) and assessing their predictive value for patient survival. Materials and methods. We classified 131 DLBCL patients using Hans algorithm into GCB (germinal center B-celllike) and ABC (activated B-cell-like) subtypes, and with NGS applying Archer FusionPlex lymphoma assay into ABC, GCB, unclassified, and into Schmitz’s novel genetic subtypes. A mutational analysis of just 7 genes (MYD88L265P, CD79B, EZH2, NOTCH1, NOTCH2, BCL2, and BCL6) was used for genetic classification. Various statistical models were applied to assess survival differences between subtypes. Finally, STRATOS analysis was conducted to validate our preliminary statistical findings. Results. 35.9% of patients were successfully classified into new genetic subtypes, with acceptable consistency between IHC and NGS method for COO determination. However, the new genetic subtype classification by NGS did not correlate with overall survival, nor did the COO classifications by IHC or NGS. The inclusion of these classifications also did not improve the predictive value of models compared to the basic model based on the International Prognostic Index (IPI) only. Conclusions. The Archer FusionPlex Lymphoma assay showed a somewhat lower detection rate of novel genetic subtypes compared to reports based on exome sequencing, yet identified novel genetic subtypes in over one-third of patients. However, an in-depth STRATOS statistical analysis did not confirm its predictive value for DLBCL prognosis, likely due to factors like patient selection and sample size limitations.
Keywords: diffuse large B-cell lymphoma, new genetic types, prognostic factors
Published in DiRROS: 26.11.2025; Views: 149; Downloads: 45
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358. Divergent trends in insect disturbance across Europe's temperate and boreal forestsTomáš Hlásny, Roman Modlinger, Jostein Gohli, Rupert Seidl, Paal Krokene, Iris Bernardinelli, Simon Blaser, Gediminas Brazaitis, Gailenė Brazaitytė, Eckehard Brockerhoff, Maarten De Groot, Marija Kolšek, 2025, original scientific article Abstract: Ongoing shifts in climate and land use have altered interactions between trees and insect herbivores, changing biotic disturbance regimes. However, as these changes are complex and vary across host species, insect taxa, and feeding guilds, they remain poorly understood. We compiled annual records of forest insect disturbance from 15 countries in temperate and boreal Europe, spanning the period from 2000 to 2022. The dataset comprises 1361 time series characterizing the dynamics of 50 herbivorous insects. We used this dataset to test whether insect disturbance has systematically changed during the 23-year period across host trees and feeding guilds, whether it varies along latitudinal and climatic gradients, and whether synchrony exists among species in the same guild or among species sharing the same host. Since 2000, borer disturbance was predominantly concentrated on gymnosperms, while defoliators impacted gymnosperms and angiosperms more evenly. While 85.8% of gymnosperm disturbance was inflicted by a single species, Ips typographus, the majority of disturbances to angiosperms were caused by six different species. Borer impact on gymnosperms has increased in the 21st century, while defoliator impact has decreased across both clades. In contrast to diverging temporal trends, disturbance was consistently greater in warmer and drier conditions across feeding guilds and host types. We identified significant synchrony in insect disturbance within host types and feeding guilds but not between these groups, suggesting shared drivers within guilds and host types. Increasing insect disturbance to gymnosperms may catalyze adaptive transformations in Europe's forests, promoting a shift from historical conifer-dominated management to broadleaved trees, which are less affected by insect herbivores. Our findings reveal a diversity of trends in insect herbivory, underscoring the need to strengthen monitoring and research in order to better understand underlying mechanisms and identify emerging threats that may not be apparent in currently available data.
Keywords: climate change, ecosystem adaptation, forest disturbance, forest insect herbivores, host tree types, insect feeding guilds
Published in DiRROS: 26.11.2025; Views: 141; Downloads: 67
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359. Targeting cystatin F activation enhances NK cell cytotoxicity in glioblastoma modelsEmanuela Senjor, Anamarija Habič, Urban Švajger, Ana Mitrović, Matic Proj, Andrej Porčnik, Borut Prestor, Miha Jerala, Matic Bošnjak, Stanislav Gobec, Barbara Breznik, Janko Kos, Milica Perišić, 2025, original scientific article Abstract: Introduction: Glioblastoma (GBM) is a highly invasive brain tumor with limited treatment options and poor prognosis. Natural killer (NK) cells are key effectors of antitumor immunity, capable of eliminating cancer stem-like cells. However, GBM creates an immunosuppressive microenvironment that limits NK cell function. Here, we identify cystatin F as an immunosuppressive factor involved in regulating NK cell granule-mediated cytotoxicity. Methods: We analyzed cystatin F expression in GBM and its correlation with immune exhaustion markers. NK cell activity was compared between GBM patients and healthy donors. In vitro co-cultures of cystatin F-expressing microglial cells and glioblastoma stem-like cells were used to assess NK cell function. To block cystatin F activation from dimeric to active monomeric form, a small-molecule inhibitor of cathepsin V, the activating protease, was applied. Results: Cystatin F expression correlated with immune exhaustion and suppression markers in GBM. NK cells from patients showed reduced cytotoxicity compared to healthy donors. Co-cultures confirmed that cystatin F-expressing microglia impaired NK cell cytotoxicity, while inhibition of cathepsin V restored NK cell function in standard cytotoxicity assays, 3D spheroids, and microfluidic perfused models. Discussion: These results indicate that cystatin F mediates NK cell suppression in GBM. Targeting its activation enhances NK cell cytotoxicity, offering a potential strategy to improve NK-based immunotherapy for glioblastoma.
Keywords: glioblastoma, cystatin F, 3D models
Published in DiRROS: 26.11.2025; Views: 109; Downloads: 102
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360. Content of trans-fatty acid isomers in bakery products on the Slovenian marketMarjeta Mencin, Helena Abramovič, Emil Zlatić, Lea Demšar, Saša Piskernik, Matthias Schreiner, Katja Žmitek, Anita Kušar, Igor Pravst, Rajko Vidrih, 2021, original scientific article Published in DiRROS: 26.11.2025; Views: 159; Downloads: 81
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