1. Editorial : brain cancer pathogenesis and data integrationAndrea Comba, Xinzhong Li, Barbara Breznik, 2023, other scientific articles Abstract: Brain tumors are one of the most aggressive malignancies in humans. They can be classified as primary tumors, which arise in the brain, or secondary tumors, which arise elsewhere in the body and initially metastaze the brain. The morbidity and mortality of brain tumors is one of the highest among cancers (Siegel et al., 2023). Of particular concern is that mortality and incidence of brain tumors are increasing, especially in the population under 44 years of age. Brain tumor mortality in this population is 13.4%. For example, primary brain tumors are the most common cancer in children and the leading cause of death in pediatric cancer patients (Gould, 2018). Considering the low survival rate of adult and pediatric brain tumor patients and the detrimental impact on patient quality of life, economic costs, and mortality rates, there is an urgent need to develop more effective therapeutic approaches. Despite major research efforts, there are currently no effective treatment modalities or prevention strategies that would significantly improve the quality of life and disease outcome of brain tumor patients.
Keywords: brain tumor, data integration, therapeutic resistance, biomarkers, liquid biopsies
Published in DiRROS: 06.08.2024; Views: 25; Downloads: 12
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2. Analysis of glioblastoma patients' plasma revealed the presence of microRNAs with a prognostic impact on survival and those of viral originKlemen Zupančič, Helena Motaln, Miomir Knežević, Urška Verbovšek, Marjan Koršič, Tamara Lah Turnšek, Primož Rožman, Matjaž Jeras, Matjaž Hren, Kristina Gruden, Andrej Blejec, Matija Veber, Ana Herman, Andrej Porčnik, Vid Podpečan, 2015, original scientific article Abstract: Background
Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions.
Experimental Procedures
MicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits.
Results
We identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients’ survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM.
Conclusion
The GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients
Keywords: microRNAs, glioblastoma multiforme, biomarkers, RNA extraction, viral disease diagnosis
Published in DiRROS: 26.07.2024; Views: 130; Downloads: 57
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3. The five-year KRAS, NRAS and BRAF analysis results and treatment patterns in daily clinical practice in Slovenia in 1st line treatment of metastatic colorectal (mCRC) patients with RASwild-type tumour (wtRAS) : a real- life data report 2013–2018Tanja Mesti, Martina Reberšek, Janja Ocvirk, 2023, original scientific article Abstract: Background. We preformed a Phase IV non-interventional study to assess KRAS, NRAS and BRAF status in metastatic colorectal cancer (mCRC) patients suitable for 1st line treatment and to evaluate the decisions for 1st line treatment considering the treatment goals in the RAS wild type (wt) patients. The aim of our study was also to evaluate the influ-ence of a waiting period for biomarkers analysis on the start of first-line treatment.Patients and methods. Patients with histologically confirmed mCRC adenocarcinoma suitable for first-line treat-ment fulfilling all inclusion criteria were included in the study. The KRAS, NRAS and BRAF analysis was performed from tissue samples of primary tumor site or metastatic site. All included patients have given consent to participate in the study by signing the informed consent form. Results. From April 2013 to March 2018 at the Institute of Oncology Ljubljana 650 patients were included, 637 of them were treated with first- line systemic treatment according to RAS and BRAF status. Remaining 13 patients with mCRC did not receive systemic first-line treatment. The distribution of patients with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively, 89 % of the patients had wt NRAS tumours and 86.1% had wt BRAF tu-mours. The most frequently prescribed treatment was bevacizumab-based therapy (53.1%), either in combination with doublet chemotherapy or with mono-chemotherapy. EGFR inhibitors cetuximab and panitumumab were prescribed in wt RAS mCRC patients (30.9%). The waiting period for biomarkers analysis was two weeks.Conclusions. Our real-world data, single centre 5-year analysis showed that the distribution between wild type and mutated type tumors of the patients with mCRC was approximately the same, as worldwide, so the Slovenian popula-tion with mCRC has the same ratio distribution of KRAS, NRAS and BRAF wild and mutated genes. We concluded that a two-week waiting period for biomarkers analysis did not influence the first line treatment decision, so it was in the accordance with the worldwide treatment guidelines based on evidence-based medicine.
Keywords: metastatic colorectal cancer, RAS and BRAF biomarkers, systemic treatment
Published in DiRROS: 25.07.2024; Views: 106; Downloads: 41
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4. Consensus molecular subtypes (CMS) in metastatic colorectal cancer : personalized medicine decisionMartina Reberšek, 2020, review article Abstract: Colorectal cancer (CRC) is one of the most common types of cancer in the world. Metastatic disease is still incurable in most of these patients, but the survival rate has improved by treatment with novel systemic chemotherapy and targeted therapy in combination with surgery. New knowledge of its complex heterogeneity in terms of genetics, epigenetics, transcriptomics and microenvironment, including prognostic and clinical characteristics, led to its classification into various molecular subtypes of metastatic CRC, called consensus molecular subtypes (CMS). The CMS classification thus enables the medical oncologists to adjust the treatment from case to case. They can determine which type of systemic chemotherapy or targeted therapy is best suited to a specific patient, what dosages are needed and in what order. Conclusions. CMS in metastatic CRC are the new tool to include the knowledge of molecular factors, tumour stroma and signalling pathways for personalized, patient-orientated systemic treatment in precision medicine.
Keywords: metastatic colorectal cancer, heterogeneity, biomarkers, consensus molecular subtype
Published in DiRROS: 12.07.2024; Views: 229; Downloads: 36
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6. Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatmentBarbara Šenk, Katja Goričar, Viljem Kovač, Vita Dolžan, Alenka Franko, 2019, original scientific article Keywords: malignant mesothelioma, genetic polymorphism, cisplatin, biomarkers
Published in DiRROS: 05.07.2024; Views: 116; Downloads: 33
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8. Biological factors of the tumour response to electrochemotherapy : review of the evidence and a research roadmapGregor Serša, Katja Uršič Valentinuzzi, Maja Čemažar, Richard Heller, Maša Omerzel, Luca Giovanni Campana, 2021, review article Abstract: The beneficial effects of electrochemotherapy (ECT) for superficial tumours and, more recently, deepseated malignancies in terms of local control and quality of life are widely accepted. However, the variability in responses across histotypes needs to be explored. Currently, patient selection for ECT is based on clinical factors (tumour size, histotype, and exposure to previous oncological treatments), whereas there are no biomarkers to predict the response to treatment. In this field, two major areas of investigation can be identified, i.e., tumour cell characteristics and the tumour microenvironment (vasculature, extracellular matrix, and immune infiltrate). For each of these areas, we describe the current knowledge and discuss how to foster further investigation. This review aims to provide a summary of the currently used guiding clinical factors and delineates a research roadmap for future studies to identify putative biomarkers of response to ECT. These biomarkers may allow researchers to improve ECT practice by customising treatment parameters, manipulating the tumour and its microenvironment, and exploring novel therapeutic combinations.
Keywords: biological factors, biomarkers, electrochemotherapy, bleomycin, cisplatin
Published in DiRROS: 23.09.2022; Views: 689; Downloads: 220
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9. Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients : a pilot studyNežka Hribernik, Daniel T. Huff, Andrej Studen, Katarina Zevnik, Žan Klaneček, Hamid Emamekhoo, Katja Škalič, Robert Jeraj, Martina Reberšek, 2022, original scientific article Abstract: Purpose: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.
Keywords: melanoma, malignant melanoma, immune-checkpoint inhibitors, molecular imaging biomarkers
Published in DiRROS: 07.09.2022; Views: 709; Downloads: 223
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10. Early biomarkers of altered renal function and orthostatic intolerance during 10-day bedrestGrazia Tamma, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Maria Venneri, Mariagrazia D'Agostino, Angela Ferrulli, Boštjan Šimunič, Marco Vicenzo Narici, Rado Pišot, Giovanna Valenti, 2022, original scientific article Abstract: Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.
Keywords: kidney, functions, bed rest, biomarkers, orthostatic intolerance, vasopressin, copeptin, aquaporin-2, adrenomedullin, calcium
Published in DiRROS: 20.04.2022; Views: 969; Downloads: 576
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