1. How beech provenance affects the structure of secondary xylem, leaf traits, and the ectomycorrhizal community under optimal growth conditionsTanja Mrak, Jožica Gričar, Tina Unuk Nahberger, Gregor Božič, Luka Krajnc, Peter Prislan, Domen Arnič, Tom Levanič, Hojka Kraigher, 2024, original scientific article Abstract: Beyond growth parameters and drought tolerance, comparatively little is known about the functioning of different beech (Fagus sylvatica L.) provenances. We investigated properties of leaves, stem secondary xylem, and ectomycorrhiza (ECM), and explored their interdependencies to identify the best performing beech provenance in optimal growth conditions. The study was conducted on 23-year-old trees in a provenance trial. The investigated provenances originated from Atlantic (Belgium—BE), Alpine (Italy—IT, Slovenia—SI), and continental climates (the Czech Republic—CZ). A significant effect of provenance was observed for stem vessel diameters and conductive area, as well as for foliar %C, δ13C, δ15N, and δ18O. δ13C as a proxy of intrinsic water use efficiency (iWUE) showed that the highest iWUE was achieved in BE provenance. Individuals with a better iWUE had wider growth rings regardless of provenance. Better iWUE was associated with lower specific leaf area (SLA). ECM community composition and diversity indices did not differ significantly among the provenances. Specific ECM taxa were associated with individuals with high SLA, δ13C, δ15N, and δ18O. In optimal growth conditions with no stress events, BE is a promising provenance due to an efficient water conducting system with high vessel diameters and conductive area, and high iWUE, while Alpine provenances showed an adaptation of their water conducting system to freezing conditions at their original locations. Integrating findings from different compartments improves our understanding of functioning of different beech provenances.
Keywords: Fagus sylvatica, provenance trial, stable isotopes, specific leaf area, xylem vessels, ectomycorrhizal fungi
Published in DiRROS: 19.04.2024; Views: 0; Downloads: 1
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2. Safety and efficacy of IL-12 plasmid DNA transfection into pig skin : supportive data for human clinical trials on gene therapy and vaccinationUrša Lampreht Tratar, Tanja Jesenko, Maša Omerzel, Alenka Seliškar, Urban Stupan, Mihajlo Djokić, Jerneja Sredenšek, Blaž Trotovšek, Gregor Serša, Maja Čemažar, 2024, original scientific article Abstract: Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.
Keywords: interleukin 12, gene electrotransfer, immunotherapy
Published in DiRROS: 18.04.2024; Views: 18; Downloads: 11
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3. Adjuvant TNF-a therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectivenessMaja Čemažar, Vesna Todorović, Janez Ščančar, Urša Lampreht Tratar, Monika Savarin, Urška Kamenšek, Simona Kranjc Brezar, Andrej Cör, Gregor Serša, 2015, original scientific article Abstract: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in DiRROS: 17.04.2024; Views: 44; Downloads: 5
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4. Poročilo : Makro in mikro analiza vzorcev lesa za identifikacijo (javor)Jožica Gričar, Gregor Skoberne, Peter Prislan, 2024, treatise, preliminary study, study Keywords: gozdarstvo, les, makro analize, mikro analize, javor, identifikacija
Published in DiRROS: 15.04.2024; Views: 64; Downloads: 12
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5. Tumor size and effectiveness of electrochemotherapyBarbara Mali, Damijan Miklavčič, Luca Giovanni Campana, Maja Čemažar, Gregor Serša, Marko Snoj, Tomaž Jarm, 2013, original scientific article Keywords: electrochemotherapy, cutaneous tumors, effectiveness, tumor size, meta-analysis
Published in DiRROS: 22.03.2024; Views: 77; Downloads: 28
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8. Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicityNina Trošt, Peter Juvan, Gregor Serša, Nataša Debeljak, 2012, original scientific article Abstract: Background. Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient's survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity. Materials and methods. Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and p53 status. Cells wer e cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression ofgenes involved in the p53-signaling pathway. Results. Short-term exposure ofbreast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression. Conclusions. Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.
Keywords: breast cancer, erythropoietin, cisplatin, cytotoxicity
Published in DiRROS: 22.03.2024; Views: 71; Downloads: 29
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9. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycinVesna Todorović, Gregor Serša, Vid Mlakar, Damjan Glavač, Maja Čemažar, 2012, original scientific article Abstract: Background. Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Materials and methods. Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Results. Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy.Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Conclusions. Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics.
Published in DiRROS: 21.03.2024; Views: 276; Downloads: 43
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10. Effects of electrochemotherapy on immunologically important modifications in tumor cellsUrša Kešar, Boštjan Markelc, Tanja Jesenko, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, original scientific article Abstract: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.
Keywords: electrochemotherapy, cisplatin, immune response
Published in DiRROS: 21.03.2024; Views: 74; Downloads: 40
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