871. Addition of 2-(ethylamino)acetonitrile group to nitroxoline results in significantly improved anti-tumor activity in vitro and in vivoAna Mitrović, Izidor Sosič, Špela Kos, Urša Lampreht Tratar, Barbara Breznik, Simona Kranjc Brezar, Bojana Mirković, Stanislav Gobec, Tamara Lah Turnšek, Maja Čemažar, Gregor Serša, Janko Kos, 2017, original scientific article Abstract: Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively. In the present study, we have evaluated its anti-cancer properties. It was more effective than nitroxoline in reducing tumor cell invasion and migration, as determined in vitro on two-dimensional cell models and tumor spheroids, under either endpoint or real time conditions. Moreover, it exhibited improved action over nitroxoline in impairing tumor growth in vivo in LPB mouse fibrosarcoma tumors in C57Bl/6 mice. Taken together, the addition of a 2-(ethylamino)acetonitrile group to nitroxoline at position 7 significantly improves its pharmacological characteristics and its potential for use as an anti-cancer drug.
Keywords: nitroxoline derivative, cathepsin B, inhibition, tumor invasion, cell migration
Published in DiRROS: 26.07.2024; Views: 286; Downloads: 227
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872. Innovative microkinetic modelling-supported structure–activity analysis of Ni/ZSM-5 during vapor-phase hydrogenation of levulinic acidHue-Tong Vu, Žan Lavrič, Andrii Kostyniuk, Goran Dražić, Miha Grilc, Blaž Likozar, Nataša Zabukovec Logar, Petar Djinović, Nataša Novak Tušar, 2024, original scientific article Published in DiRROS: 26.07.2024; Views: 351; Downloads: 649
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873. Mejice kot podpora biotski raznolikosti, ohranjanju tradicionalnega in izginjajočega kulturnega vzorca slovenskega podeželja ter zagotavljanju ekosistemskih storitev : priročnik dobre prakseTine Grebenc, Ajša Alagić, Nejc Suban, Benjamin Leskovec, Polona Urh, Jani Gačnik, Jure Štanta, Tamara Urbančič, Tine Božič, Matevž Podjed, Maja Košuta, 2024, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: mejice, priročniki, ekosistemske storitve, kmetijsko gospodarstvo, praktični preskus, plodonosnost, gomoljke
Published in DiRROS: 26.07.2024; Views: 485; Downloads: 194
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874. Phase angle as a prognostic indicator of surgical outcomes in patients with gastrointestinal cancerJana Gulin, Ester Ipavic, Denis Mlakar-Mastnak, Erik Brecelj, Ibrahim Edhemović, Nada Rotovnik-Kozjek, 2023, original scientific article Keywords: phase angle, colorectal cancer, postoperative complications, malnutrition
Published in DiRROS: 26.07.2024; Views: 507; Downloads: 80
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876. The association of genetic factors with serum calretinin levels in asbestos-related diseasesCita Zupanc, Alenka Franko, Danijela Štrbac, Viljem Kovač, Vita Dolžan, Katja Goričar, 2023, original scientific article Abstract: Background. Asbestos exposure is associated with different asbestos-related diseases, including malignant meso-thelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymor-phisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.Subjects and methods. The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.Results. Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335genotypes.Conclusions. The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diag-nosis.
Keywords: malignant mesothelioma, calretinin, CALB2, asbestos-related disease, polymorphism
Published in DiRROS: 26.07.2024; Views: 471; Downloads: 166
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877. The prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinomaSimona Miceska, Erik Škof, Simon Buček, Cvetka Grašič-Kuhar, Gorana Gašljević, Špela Smrkolj, Veronika Kloboves-Prevodnik, 2023, original scientific article Abstract: Background: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our finBackground: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings.dings.
Keywords: high-grade serous carcinoma, immune cells, prognostic markers
Published in DiRROS: 26.07.2024; Views: 525; Downloads: 226
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878. The most suitable time and depth to sample Cymodocea nodosa (Ucria) Ascherson meadows in the shallow coastal area. Experiences from the northern Adriatic SeaMartina Orlando-Bonaca, Lovrenc Lipej, Janja Francé, 2016, original scientific article Abstract: The Lesser Neptune grass, Cymodocea nodosa, is the most common seagrass species in shallow sheltered to semi-exposed sites along the Mediterranean soft bottom. The MediSkew index was recently developed as an improvement of the CymSkew index, in order to assess the status of C. nodosa meadows correctly in view of the implementation of three European Directives. The index takes into account the length of the photosynthetic part of C. nodosa leaves, which increases from the less degraded meadow to the most degraded meadow. To adequately assess temporal and spatial trends in the status of C. nodosa meadows, including estimates of the effects of natural disturbances within marine protected areas, the MediSkew index was applied to new samples collected at 3 m and at 6 m of depth, during two months (in July and in September). The analyses are discussed in view of monitoring and conservation of C. nodosa meadows. According to the results of this study, the monitoring programme in the northern Adriatic Sea should be conducted in July, with the collection of samples at 3 m of depth. The presented sampling and assessing methodology proved to be time- and cost-effective for the evaluation of the status of C. nodosa meadows and of human-induced pressures.
Keywords: MediSkew index, leaf lengths, Lesser Neptune grass, northern Adriatic Sea
Published in DiRROS: 26.07.2024; Views: 253; Downloads: 145
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879. Imaging microvascular changes in nonocular oncological clinical applications by optical coherence tomography angiography : a literature reviewRok Hren, Gregor Serša, Urban Simončič, Matija Milanič, 2023, review article Keywords: optical coherence tomography, angiography, endoscopy, oncology, skin carcinoma
Published in DiRROS: 26.07.2024; Views: 481; Downloads: 197
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880. Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer : study protocol for phase I clinical trialPrimož Strojan, Gaber Plavc, Marko Kokalj, Goran Mitrović, Olga Blatnik, Luka Ležaič, Aljaž Sočan, Aljoša Bavec, Nataša Tešić, Katrina Pretnar-Hartman, Urban Švajger, 2023, original scientific article Abstract: Background: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue. Methods: Ten oropharyngeal cancer patients with post-radiation xerostomia and no evidence of disease recurrence 2 or more years after (chemo)irradiation (intervention group) and 10 healthy volunteers (control group) will be enrolled in this nonrandomized, open-label, phase I exploratory study. MSCs from umbilical cord tissue will be inserted under ultrasound guidance into both parotid glands and both submandibular glands of the patients. Toxicity of the procedure will be assessed according to CTCAE v5.0 criteria at days 0, 1, 5, 28, and 120. Efficacy will be assessed by measuring salivary flow and analyzing its composition, scintigraphic evaluation of MSC grafting, retention, and migration, and questionnaires measuring subjective xerostomia and quality of life. In addition, the radiological, functional, and morphological characteristics of the salivary tissue will be assessed before, at 4 weeks, and at 4 months after the procedure. In the control group subjects, only salivary flow rate and salivary composition will be determined. Discussion: The use of allogeneic MSCs from umbilical cord tissue represents an innovative approach for the treatment of xerostomia after radiation. Due to the noninvasive collection procedure, flexibility of cryobanking, and biological advantages, xerostomia therapy using allogeneic MSCs from umbilical cord tissue may have an advantage over other similar therapies.
Keywords: oropharyngeal cancer, xerostomia, mesenchymal stromal stem cells
Published in DiRROS: 26.07.2024; Views: 473; Downloads: 227
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