Projects

Ecotoxicology, Toxicogenomics and Carcinogenesis

Holder: Bojana Žegura, PhD

Code: P1-0245

Duration: 1. 1. 2019 - 31. 12. 2024

ARRS programme J1-2465

Holder: Assist. prof. Bojana Žegura (till 31.12.2020 prof.dr. Tamara Lahko Turnšek)

Duration: 1.1.1999―31.12.2024

Title: Ecotoxicology, toxicogenomics and carcinogenesis

Researchers: link to database SICRIS

Information about the programme: link to database SICRIS


Toxic pollutants as well as irradiation represent a serious threat for the natural environment and human health. The origin of chemical pollution are fabricated compounds released to the environment as well as natural compounds produced by various organisms. Despite growing evidence for the presence of these compounds in air, soil and water and consequently in the food to which we are exposed, there are still gaps in our understanding how these chemicals affect living organisms, which make rational risk assessment for the environment and human health impossible, particularly the cancer risk assessment. Another not well understood threat is environmental ionizing radiation, which has been recently addressed by the International Union of Radioecology.
This Programme aims at the study of the effects of anthropogenic and natural toxicants including irradiation in the environment and their role in cancer initiation and development. The major platforms are: (I) The effects of toxic pollutants and irradiation on environment and human health and (II) Cancer initiation and development. These platforms are supported by technological actions comprising (III) Develop new alternatives for animal assays.



Objectives of the Programme

In this Programme we intend to apply a holistic approach for studying potential adverse effects of toxic pollutants and irradiation and cancer initiating events, both lines of research being supported by upgraded state of the art methodology that are replacing higher animal species in the in vivo research. In toxicology, 3D human liver-like cell systems and zebrafish embryo will be used to elucidate specific mechanism of genotoxic compounds action, which may lead to carcinogenic mutations, whereas endocrine disrupting compounds lead to decreased reproduction and other diseases. Brain cancer glioblastoma initiating cells and their pathobiological interactions with their microenvironment will be tested in innovative models of stem cell niches. The objective is to increase the response of GBM stem cells to therapy by manipulating the genes related to stemness and therapy resistance and/or interfere with GSC niche structures. In this way, we aim to increase the effectiveness of standard therapies and lower irradiation dose to reduce side effects.

 

Specific aims are:

Topic I. The effects of toxic pollutants and irradiation on environment and human health

  1.         To understand environmental and human health effects of genotoxic pollutants, endocrine disruptors and irradiation through mechanism-based toxicological characterization in realistic exposure conditions.
  2.        To develop and provide new models and tools to assess ecotoxicological and ecological characteristics of polluted aquatic environments and impacts on biodiversity.

Topic II. Cancer initiation and development

  1.           To address intra-tumoral heterogeneity and determine GBM subtypes by gene fingerprinting (proneural versus mesenchymal) in GBM samples of a large cohort of patients before and after irradiation or chemotherapy to functionally establish the clinical observation that GBM tumour relapses are often more aggressive.
  2.            To interfere with radio-resistance of GSCs by downregulation of the expression of GSC stemness-related genes and anti-apoptotic genes which are preventing cell death.
  3.          To develop in vitro GSC niches by 3D multicellular cocultures of GSC and various types of stromal cells to study their interactions before and after irradiation and/or manipulation of the expression of specific genes.
  4.            To develop a Slovenian GBM biobank via collaborative interinstitutional initiatives.

Topic III. New alternatives to animal assays

  1.          To support the above tasks by development of innovative 3D spheroid cell and tissue models.
  2.          To upgrade the currently used zebrafish embryo models for specific tasks in toxicological research and in cancer research.




(I) The effects of toxic pollutants and irradiation on the environment and human health

Genotoxic and endocrine-disrupting pollutants are of particular concern among the numerous toxic environmental contaminants. A common key characteristic is that they exert their adverse effects with a delay and at low concentrations particularly during chronic exposure. We are studying direct and indirect interactions at the molecular and cellular levels as well as at the level of whole organisms. Researchers are studying the action of tyrosine kinase inhibitors (TKIs), which belong to the group of anticancer drugs. Due to their increasing presence in the environment and their potential harming action, they investigate their acute and sub lethal effects in embryos of zebrafish, complementing the phenotypic changes with transcriptomic level studies. The harmful genotoxic effects of TKIs are also being studied in in vitro human cell models to determine whether residues of TKIs in the environment pose a risk to the environment and human health. Research on mechanisms of toxic and genotoxic actions of cyanobacterial toxins is aimed at studying the combinational effects of toxins with other pollutants, such as bisphenols, which may be exposed in nature at the same time. This kind of research is important because there may be interactions between pollutants, the effects of which may be completely different from what you would expect based on toxicological data for individual compounds. Applied research on the ecological status of inland waters is being shifted to research and development of new methodologies for assessing the ecological status of inland waters, based on the use of advanced next-generation DNA sequencing techniques, which are becoming more and more internationally recognized. The presence of certain toxic species of toxigenic cyanobacteria will be evaluated. Due to their frequent occurrence in lakes and reservoirs and, consequently, drinking water, humans can also be exposed to cyanotoxins, so controlling and preventing cyanobacterial growth is of paramount importance. The lack of clean water is one of the greatest risks, especially in times of global and local climate change.


(II) Cancer initiation and development

The cancer research group will continue to investigate the role and impact of cancer stem cells, specifically glioblastoma stem cells (GB SC = GSC), on the development and progression of glioblastoma. The research will focus on understanding the role of a new markers for these cells, such as the tetraspanin CD9, which we also described it first in the literature to be important for maintaining GSC stem properties. In the future, we will investigate how the deletion of this gene could reduce the therapeutic resistance of GSC cells, which is crucial for poor prognosis for patient survival. Research will also focus on studying the susceptibility of GSC / GB cells to the effects of gamma radiation (in collaboration with the Institute of Oncology and the University of Innsbruck). As an example of the influence of the tumor microenvironment or. stromal cells on GB, we will investigate the effects of mesenchymal stem cells (MSCs) in tumor niches where GSC are located. The role of MSCs in this context is still unclear, but these cells may also be a target for therapy, as they are assumed to participate in cancer progression. We will continue transnational  Interreg project TRANSGLIOMA from 2017, where they are building a joint, inter-regional tumor bank. New multi-cell and 3-dimensional cell models are being studied for complex cellular interactions and, on the other hand, the influence of drugs and natural compounds. In this regard, we will focus on cannabinoids, the research of which we have already begun this year. We will also continue our experiments with the study of GB in vivo in embryos of zebrafish.


(III) New alternatives to animal assays

(i) In the field of genetic toxicology, research to date has shown that in the 3D matrix, model liver cells retain physiologically relevant functions and therefore better reflect the in vivo state. That is why we are developing advanced liver 3D cellular systems grown under static and dynamic conditions. For the purposes of genetic toxicology, standard tests (comet test, gama-H2AX test and micronucleus test) are adapted to spheroid models. We focus on the development of metabolically active liver 3D cell models that represent the bridge between classic 2D cell systems and animal experiments.
(ii) We use 3D spheroid models in the fields of cancer research as they are the basis for the study of cancer stem cells and their microenvironment. We focus on organotypic, multicellular models of cancer / cancer stem cells or organotypic models involving the microenvironment. These models are extremely important for drug testing and development, including cannabinoids.
(iii) Years ago, we introduced an experimental model with embryos of zebrafish, which is applicable to both branches of research. In the field of research on the effects of pollutants on the environment and human health, we are developing a system for detecting the genotoxic and endocrine effects of micro-pollutants at the molecular, cellular and organismal levels, with the aim of developing an even more reliable test system for rapid detection and identification of potentially long-term effects of pollution. In the field of cancer research, we have developed a model that enables the monitoring of human glioblastoma cell invasion, which is applied in mechanistic and potential new drug research.


In addition to responding to the pandemic situation, caused by the SARS-CoV-2 virus, the GEN Department researchers have also suggested incorporating this research into the program to shed light on these issue or the potential use of our knowledge and expertise in developing methods of protection and treatment, such as:
• Testing of biocompatibility and safety of materials (according to ISO standard ISO 10993-5 and ISO 10993-12) of protective equipment (masks, gloves) and medical devices, since new products are on the market from unverified materials.
• Testing the safety of the new disinfectants that can be harmful to human health and the environment. Currently, disinfectants of external and internal surfaces (chlorine in combination with organic compounds can form carcinogenic trihalomethane and the like) are widely used, which can lead to delayed action.
• Research and development of protease inhibitors that can prevent the entry of the virus into the lung epithelial cells to inhibit serine protease-associated processes and in the later stages of the triggered inflammation of cysteine protease inhibitors in the pulmonary alveoli.
• Validation and development of effective therapeutic mesenchymal stem cells (MSCs) that have been proven effective in acute respiratory distress syndrome (ARDS) and in the treatment of very similar symptoms of the disease.
• Reduction of the outbreak of the second-stage COVID-19 inflammatory processes  with the effects of cannabinoids, such as CBD (cannabidiol), which is already used to mitigate the adverse effects of many inflammatory conditions, similar to those in CoV-2 caused inflammations, thereby reducing the need for respiratory devices.


Publications from the field Ecotoxicology and genetic toxicology

2021
ŠTAMPAR, Martina, ŽABKAR, Sonja, FILIPIČ, Metka, ŽEGURA, Bojana. HepG2 spheroids as a biosensor-like cell-based system for (geno)toxicity assessment. Chemosphere, ISSN 0045-6535. [Print ed.], Nov. 2021, 1-35, https://www.sciencedirect.com/science/article/pii/S004565352103277X#!, doi: 10.1016/j.chemosphere.2021.132805.

NOVAK, Matjaž, BAEBLER, Špela, ŽEGURA, Bojana, ROTTER, Ana, GAJSKI, Goran, GERIĆ, Marko, GARAJ VRHOVAC, Verica, BAKOS, Katalin, CSENKI, Zsolt, KOVÁCS, Róbert, HORVÁTH, Ákos, GAZSI, Gyöngyi, FILIPIČ, Metka. Deregulation of whole-transcriptome gene expression in zebrafish (Danio rerio) after chronic exposure to low doses of imatinib mesylate in a complete life cycle study. Chemosphere, ISSN 0045-6535. [Print ed.], Jan. 2021, vol. 263, [article] 128097, 1-10, doi: 10.1016/j.chemosphere.2020.128097.

ŠTERN, Alja, FURLAN, Veronika, NOVAK, Matjaž, ŠTAMPAR, Martina, KOLENC, Zala, KORES, Katarina, FILIPIČ, Metka, BREN, Urban, ŽEGURA, Bojana. Chemoprotective effects of xanthohumol against the carcinogenic mycotoxin aflatoxin B1. Foods, ISSN 2304-8158, 9 June 2021, vol. 10, iss. 6, 1-19, doi: 10.3390/foods10061331.

HOJNIK, Nataša, MODIC, Martina, WALSH, James L., ŽIGON, Dušan, JAVORNIK, Uroš, PLAVEC, Janez, ŽEGURA, Bojana, FILIPIČ, Metka, CVELBAR, Uroš. Unravelling the pathways of air plasma induced aflatoxin B1 degradation and detoxification. Journal of hazardous materials, ISSN 0304-3894. [Print ed.], Sep. 2021, vol. 403, 1-29, https://www.sciencedirect.com/science/article/pii/S030438942031579X, doi: 10.1016/j.jhazmat.2020.123593.

AJDNIK, Urban, LUXBACHER, Thomas, VESEL, Alenka, ŠTERN, Alja, ŽEGURA, Bojana, TRČEK, Janja, FRAS ZEMLJIČ, Lidija. Polysaccharide-based bilayer coatings for biofilm-inhibiting surfaces of medical devices. Materials, ISSN 1996-1944, Aug. 2021, vol. 14, iss. 16, 1-22, ilustr. https://www.mdpi.com/1996-1944/14/16/4720, doi: 10.3390/ma14164720.

ŠTAMPAR, Martina, FRANDSEN, Helle, ROGOWSKA-WRZESINSKA, Adelina, WRZESINSKI, Krzysztof, FILIPIČ, Metka, ŽEGURA, Bojana. Hepatocellular carcinoma (HepG2/C3A) cell-based 3D model for genotoxicity testing of chemicals. Science of the total environment, ISSN 1879-1026. [Online ed.], 2021, vol. 755, pt. 2, 1-12, https://www.sciencedirect.com/science/article/pii/S0048969720367863, doi: 10.1016/j.scitotenv.2020.143255.

BALABANIČ, Damjan, FILIPIČ, Metka, KRIVOGRAD-KLEMENČIČ, Aleksandra, ŽEGURA, Bojana. Genotoxic activity of endocrine disrupting compounds commonly present in paper mill effluents. Science of the total environment, ISSN 0048-9697, June 2021, vol. 768, 1-49, https://www.sciencedirect.com/science/article/pii/S0048969721035610?via%3Dihub, doi: 10.1016/j.scitotenv.2021.148489.

BITTNER, Michal, ŠTERN, Alja, SMUTNA, Marie, HILSCHEROVA, Klara, ŽEGURA, Bojana. Cytotoxic and genotoxic effects of cyanobacterial and algal extracts-microcystin and retinoic acid content. Toxins : Elektronski vir, ISSN 2072-6651, 2021, vol. 13, no. 2, 1-15. https://www.mdpi.com/2072-6651/13/2/107. [COBISS.SI-ID 49665283], [JCR, SNIP]

2020

HERCOG, Klara, ŠTERN, Alja, MAISANABA HERNÁNDEZ, Sara, FILIPIČ, Metka, ŽEGURA, Bojana. Plastics in cyanobacterial blooms - genotoxic effects of binary mixtures of cylindrospermopsin and bisphenols in HepG2 cells. Toxins : Elektronski vir, ISSN 2072-6651, 2020, vol. 12, iss. 4, str. 1-19, ilustr. https://www.mdpi.com/2072-6651/12/4/219.

BERGANT LOBODA, Kaja, VALJAVEC, Katja, ŠTAMPAR, Martina, WOLBER, Gerhard, ŽEGURA, Bojana, FILIPIČ, Metka, SOLLNER DOLENC, Marija, PERDIH, Andrej. Design and synthesis of 3,5-substituted 1,2,4-oxadiazoles as catalytic inhibitors of human DNA topoisomerase IIα. Bioorganic chemistry, ISSN 0045-2068, 2020, vol. 99, 103828-1 - 103828-19, https://www.sciencedirect.com/science/article/pii/S0045206820301218?dgcid=author, doi: 10.1016/j.bioorg.2020.103828.

ŠTAMPAR, Martina, BREZNIK, Barbara, FILIPIČ, Metka, ŽEGURA, Bojana. Characterization of In vitro 3D cell model developed from human hepatocellular carcinoma (HepG2) cell line. Cells, ISSN 2073-4409, Nov. 2020, vol. 9, iss. 12, 1-19, https://www.mdpi.com/2073-4409/9/12/2557, doi: 10.3390/cells9122557.

UJVÁROS, Andrea Zsuzsanna, HERCOG, Klara, RIBA, Milán, GONDA, Sándor, FILIPIČ, Metka, VASAS, Gábor, ŽEGURA, Bojana. The cyanobacterial oligopeptides microginins induce DNA damage in the human hepatocellular carcinoma (HepG2) cell line. Chemosphere, ISSN 0045-6535. [Print ed.], 2020, vol. 240, 1-11. https://www.sciencedirect.com/science/article/pii/S0045653519321198, doi: 10.1016/j.chemosphere.2019.124880.

MØLLER, Peter, AZQUETA, Amaya, BOUTET-ROBINET, Elisa, KOPPEN, Gudrun, BONASSI, Stefano, MILIĆ, Mirta, GAJSKI, Goran, COSTA, Solange, ŽEGURA, Bojana, NOVAK, Matjaž, et al. Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results. Nature protocols, ISSN 1750-2799. [Online ed.], 2020, vol. 15, iss. 12, 3817-3826,  https://www.nature.com/articles/s41596-020-0398-1, doi: 10.1038/s41596-020-0398-1.

2019

ŠTAMPAR, Martina, TOMC, Jana, FILIPIČ, Metka, ŽEGURA, Bojana. Development of in vitro 3D cell model from hepatocellular carcinoma (HepG2) cell line and its application for genotoxicity testing. Archives of toxicology, ISSN 0340-5761, 2019, vol. , iss. , 13, [in press], doi: 10.1007/s00204-019-02576-6.


HERCOG, Klara, MAISANABA HERNÁNDEZ, Sara, FILIPIČ, Metka, SOLLNER DOLENC, Marija, KAČ, Lidija, ŽEGURA, Bojana. Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells.
Science of the total environment, ISSN 0048-9697, Oct. 2019, vol. 687, 267-276, ilustr. https://www.sciencedirect.com/science/article/pii/S004896971932546X, doi: 10.1016/j.scitotenv.2019.05.486.


MIŠÍK, Miroslav, FILIPIČ, Metka, NERSESYAN, Armen, KUNDI, Michael, ISIDORI, Marina, KNASMÜELLER, Siegfried. Environmental risk assessment of widely used anticancer drugs (5-fluorouracil, cisplatin, etoposide, imatinib mesylate).
Water research, ISSN 0043-1354. [Print ed.], 2019, vol. , 34, [in press], doi: 10.1016/j.watres.2019.114953.


GERIĆ, Marko, GAJSKI, Goran, DOMIJAN, Ana-Marija, GARAJ VRHOVAC, Verica, FILIPIČ, Metka, ŽEGURA, Bojana. Genotoxic effects of neurotoxin ß-N-methylamino-L-alanine in human peripheral blood cells. Chemosphere, ISSN 0045-6535. [Print ed.], 2019, vol. 214, 623-632, doi: 10.1016/j.chemosphere.2018.09.155.

2018
WALDHERR, Monika, MIŠÍK, Miroslav, FERK, Franziska, TOMC, Jana, ŽEGURA, Bojana, FILIPIČ, Metka, MIKULITS, Wolfgang, MAI, Sören, HAAS, Oskar, HUBER, Wolfgang W., HASLINGER, Elisabeth, KNASMÜLLER, Siegfried. Use of HuH6 and other human-derived hepatoma lines for the detection of genotoxins : a new hope for laboratory animals?. Archives of toxicology, ISSN 0340-5761, 2018, vol. 92, iss. 2, str. 921-934, doi: 10.1007/s00204-017-2109-4.


HERCOG, Klara, MAISANABA HERNÁNDEZ, Sara, FILIPIČ, Metka, JOS, Angeles, CAMEÁN, Ana M, ŽEGURA, Bojana. Genotoxic potential of the binary mixture of cyanotoxins Microcystin-LR and cylindrospermopsin.
Chemosphere, ISSN 0045-6535. [Print ed.], 2017, vol. 189, str. 319-329. http://dx.doi.org/10.1016/j.chemosphere.2017.09.075, doi: 10.1016/j.chemosphere.2017.09.075.


NOVAK, Matjaž, ŽEGURA, Bojana, NUNIĆ, Jana, GAJSKI, Goran, GERIĆ, Marko, GARAJ-VRHOVAC, Vera, FILIPIČ, Metka. Assessment of the genotoxicity of the tyrosine kinase inhibitor imatinib mesylate in cultured fish and human cells.
Mutation research, Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, 2017, vol. 814, str. 14-21, doi: 10.1016/j.mrgentox.2016.12.002

ELERŠEK, Tina, ŽENKO, Maja, FILIPIČ, Metka. Ecotoxicity of disinfectant benzalkonium chloride and its mixture with antineoplastic drug 5-fluorouracil towards alga Pseudokirchneriella subcapitata. PeerJ, ISSN 2167-8359, 18. jun. 2018, str. 1-14. https://peerj.com/articles/4986.pdf, doi: 10.7717/peerj.4986.


MANTZOUKI, Evanthia, REMEC-REKAR, Špela, ELERŠEK, Tina, et al. A European multi lake survey dataset of environmental variables, phytoplankton pigments and cyanotoxins. Scientific data, ISSN 2052-4463, 2018, vol. 5, str. [1-13], ilustr. http://dx.doi.org/10.1038/sdata.2018.226, doi: 10.1038/sdata.2018.226.


2017

NOVAK, Matjaž, ŽEGURA, Bojana, MODIC, Barbara, HEATH, Ester, FILIPIČ, Metka. Cytotoxicity and genotoxicity of anticancer drug residues and their mixtures in experimental model with zebrafish liver cells. Science of the total environment, ISSN 0048-9697, 2017, vol. 601/602, str. 293-300, doi: 10.1016/j.scitotenv.2017.05.115.


HERCOG, Klara, MAISANABA HERNÁNDEZ, Sara, FILIPIČ, Metka, JOS, Angeles, CAMEÁN, Ana M, ŽEGURA, Bojana. Genotoxic potential of the binary mixture of cyanotoxins Microcystin-LR and cylindrospermopsin.
Chemosphere, ISSN 0045-6535. [Print ed.], 2017, vol. 189, str. 319-329. http://dx.doi.org/10.1016/j.chemosphere.2017.09.075, doi: 10.1016/j.chemosphere.2017.09.075.


MAISANABA HERNÁNDEZ, Sara, HERCOG, Klara, ORTUÑO, Natalia, JOS, Angeles, ŽEGURA, Bojana. Induction of micronuclei and alteration of gene expression by an organomodified clay in HepG2 cells.
Chemosphere, ISSN 0045-6535. [Print ed.], 2016, vol. 154, str. 240-248. http://dx.doi.org/10.1016/j.chemosphere.2016.03.115, doi: 10.1016/j.chemosphere.2016.03.115.


ISIDORI, Marina, LAVORGNA, Margherita, RUSSO, Chiara, KUNDI, Michael, ŽEGURA, Bojana, NOVAK, Matjaž, FILIPIČ, Metka, MIŠÍK, Miroslav, KNASMÜELLER, Siegfried, LOPEZ DE ALDA, Miren, BARCELÓ, Damià, ŽONJA, Božo, ČESEN, Marjeta, ŠČANČAR, Janez, KOSJEK, Tina, HEATH, Ester. Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain.
Environmental pollution, ISSN 0269-7491. [Print ed.], 2016, vol. 219, str. 275-287. http://dx.doi.org/10.1016/j.envpol.2016.10.039, doi: 10.1016/j.envpol.2016.10.039.


BALABANIČ, Damjan, FILIPIČ, Metka, KRIVOGRAD-KLEMENČIČ, Aleksandra, ŽEGURA, Bojana. Raw and biologically treated paper mill wastewater effluents and the recipient surface waters : cytotoxic and genotoxic activity and the presence of endocrine disrupting compounds.
Science of the total environment, ISSN 0048-9697, 2017, vol. 574, str. 78-89, doi: 10.1016/j.scitotenv.2016.09.030.


2016
MAISANABA HERNÁNDEZ, Sara, HERCOG, Klara, FILIPIČ, Metka, JOS, Angeles, ŽEGURA, Bojana. Genotoxic potential of Montmorillonite clay mineral and alteration in the expression of genes involved in toxicity mechanisms in the human hepatoma cell line HepG2. Journal of hazardous materials, ISSN 0304-3894. [Print ed.], 2016, vol. 304, str. 425-433, ilustr., doi: 10.1016/j.jhazmat.2015.10.018.

KOVÁCS, Róbert, CSENKI, Zsolt, BAKOS, Katalin, URBÁNYI, Béla, HORVÁTH, Ákos, GARAJ-VRHOVAC, Vera, GAJSKI, Goran, GERIĆ, Marko, NEGREIRA, Noelia, LOPEZ DE ALDA, Miren, BARCELÓ, Damià, HEATH, Ester, KOSJEK, Tina, ŽEGURA, Bojana, NOVAK, Matjaž, ZAJC, Irena, BAEBLER, Špela, ROTTER, Ana, RAMŠAK, Živa, FILIPIČ, Metka. Assessment of toxicity and genotoxicity of low doses of 5-fluorouracil in zebrafish (Danio rerio) two-generation study. Water research, ISSN 0043-1354. [Print ed.], 2015, vol. 77, str. 201-212, doi: 10.1016/j.watres.2015.03.025.

ELERŠEK, Tina, MILAVEC, Sara, KOROŠEC, Maša, BREZOVŠEK, Polona, NEGREIRA, Noelia, ŽONJA, Božo, LOPEZ DE ALDA, Miren, BARCELÓ, Damià, HEATH, Ester, ŠČANČAR, Janez, FILIPIČ, Metka. Toxicity of the mixture of selected antineoplastic drugs against aquatic primary producers. Environmental science and pollution research international, ISSN 0944-1344. [Print ed.], 2016, vol. 23, iss. 15, 14780-14790. http://dx.doi.org/10.1007/s11356-015-6005-2, doi: 10.1007/s11356-015-6005-2.



P
ublications from the field Cancer biology

2021
MAJC, Bernarda, NOVAK, Metka, KOPITAR-JERALA, Nataša, JEWETT, Anahid, BREZNIK, Barbara. Immunotherapy of glioblastoma: current strategies and challenges in tumor model development. Cells. 29 Jan. 2021, iss. 2, [article] 265, 1-22, ISSN 2073-4409. https://www.mdpi.com/2073-4409/10/2/265/htm, DOI: 10.3390/cells10020265.

HIRA, Vashendriya V. V., MOLENAAR, Remco J., BREZNIK, Barbara, LAH TURNŠEK, Tamara, ARONICA, Eleonora, NOORDEN, Cornelis J. F. van. Immunohistochemical detection of neural stem cells and glioblastoma stem cells in the subventricular zone of glioblastoma patients. The Journal of histochemistry and cytochemistry. 2021, vol. 69, no. 5, 349-364, ISSN 0022-1554. https://journals.sagepub.com/doi/pdf/10.1369/0022155421994679, DOI: 10.1369/0022155421994679

LAH TURNŠEK, Tamara, NOVAK, Metka, PENA ALMIDON, Milagros A., MARINELLI, Oliviero, ŽVAR BAŠKOVIČ, Barbara, MAJC, Bernarda, MLINAR, Mateja, BOŠNJAK, Roman, BREZNIK, Barbara, ZOMER, Roby, NABISSI, Massimo. Cannabigerol is a potential therapeutic agent in a novel combined therapy for glioblastoma. Cells. 4 Feb. 2021, vol. 10, [article] 340, 1-21, ISSN 2073-4409. https://www.mdpi.com/2073-4409/10/2/340, DOI: 10.3390/cells10020340.

PORČNIK, Andrej, NOVAK, Metka, BREZNIK, Barbara, MAJC, Bernarda, HRASTAR, Barbara, ŠAMEC, Neja, ZOTTEL, Alja, JOVCHEVSKA, Ivana, VITTORI, Miloš, ROTTER, Ana, KOMEL, Radovan, LAH TURNŠEK, Tamara. TRIM28 selective nanobody reduces glioblastoma stem cell invasion. Molecules. Aug. 2021, vol. 26, iss. 17, 1-16, ISSN 1420-3049. https://www.mdpi.com/1420-3049/26/17/5141, DOI: 10.3390/molecules26175141.

SENJOR, Emanuela, PERIŠIĆ, Milica, BREZNIK, Barbara, MITROVIĆ, Ana, MLAKAR, Jernej, ROTTER, Ana, PORČNIK, Andrej, LAH TURNŠEK, Tamara, KOS, Janko. Cystatin F acts as a mediator of immune suppression in glioblastoma. Cellular oncology. [in press] 2021, 13, ISSN 2211-3436. DOI: 10.1007/s13402-021-00618-9.

HABIČ, Anamarija, NOVAK, Metka, MAJC, Bernarda, LAH TURNŠEK, Tamara, BREZNIK, Barbara. Proteases regulate cancer stem cell properties and remodel their microenvironment. Journal of histochemistry and cytochemistry. [Online ed.]. 26 Jul. 2021, vol. , iss. , 1-20. ISSN 1551-5044. https://journals.sagepub.com/eprint/YQQ85PXFRP4UY53ZZNIR/full, DOI: 10.1369/00221554211035192.

2020
LAH TURNŠEK Tamara, NOVAK, Metka, BREZNIK, Barbara. 2020 Brain malignancies: Glioblastoma and brain metastases. Seminars in Cancer Biology, 60(October 2019), 262–273. https://doi.org/10.1016/j.semcancer.2019.10.010

BREZNIK, Barbara, MITROVIĆ, Ana, LAH TURNŠEK, Tamara, KOS, Janko. Cystatins in cancer progression : more than just cathepsin inhibitors. Biochimie, ISSN 0300-9084, 2019, 53, doi: 10.1016/j.biochi.2019.05.002.

BREZNIK, Barbara, MOTALN, Helena, LAH TURNŠEK, Tamara. Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours. Biological chemistry, ISSN 1431-6730, 2017, vol. 398, no. 7, 709-719, doi: 10.1515/hsz-2016-0283.

2019
NEVES OLIVEIRA, Mona das, BREZNIK, Barbara, PILLAT, Micheli M., PEREIRA, Ricardo L., ULRICH, Henning, LAH TURNŠEK, Tamara. Kinins in glioblastoma microenvironment. Cancer microenvironment. 2019, 20 str., [in press]. ISSN 1875-2292. DOI: 10.1007/s12307-019-00229-x.

HIRA, Vashendriya V. V., BREZNIK, Barbara, VITTORI, Miloš, JONG, Annique Loncq de, MLAKAR, Jernej, OOSTRA, Roelof-Jan, KHURSHED, Mohammed, MOLENAAR, Remco J., LAH TURNŠEK, Tamara, NOORDEN, Cornelis J. F. van. Similarities between stem cell niches in glioblastoma and bone marrow: rays of hope for novel treatment strategies. The Journal of histochemistry and cytochemistry. 2019, 25 str., [in press]. ISSN 0022-1554. DOI: 10.1369/0022155419878416.

2018

BREZNIK, B., LIMBAECK STOKIN, C., KOS, J., KHURSHED, M., HIRA, V. V. V, BOŠNJAK, R., … VAN NOORDEN, C. J. F. (2018). Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches. Journal of Molecular Histology, 49(5), 481–497. https://doi.org/10.1007/s10735-018-9787-y

TOMC, Jana, KOLOŠA, Katja, ŽEGURA, Bojana, KAMENŠEK, Urška, BREZNIK, Barbara, LAH TURNŠEK, Tamara, FILIPIČ, Metka. Adipose tissue stem cell-derived hepatic progenies as an in vitro model for genotoxicity testing. Archives of toxicology, 2018, 11p doi: 10.1007/s00204-018-2190-3

NEVES OLIVEIRA, Mona das, PILLAT, Micheli M., MOTALN, Helena, ULRICH, Henning, LAH TURNŠEK, Tamara. Kinin-B1 receptor stimulation promotes invasion and is involved in cell-cell interaction of co-cultured glioblastoma and mesenchymal stem cells. Scientific reports, ISSN 2045-2322, 2018,  8,p. 1299-1-1299-16, doi: 10.1038/s41598-018-19359-1.


2017

HIRA, Vashendriya V. V., VERBOVŠEK, Urška, BREZNIK, Barbara, SRDIČ, Matic, NOVINEC, Marko, KAKAR, Hala, WORMER, Jill, SWAAN, Britt van der, LENARČIČ, Brigita, JULIANO, Luiz, MEHTA, Shwetal, NOORDEN, Cornelis J. F. van, LAH TURNŠEK, Tamara. Cathepsin K cleavage of SDF-1[alpha] inhibits its chemotactic activity towards glioblastoma stem-like cells. Biochimica et biophysica acta. BBA, Molecular cell research, ISSN 0167-4889. [Print ed.], 2017, vol. 1864, no. 3, p 594-603,

PRIMON, Monika, HUSZTHY, Peter C., MOTALN, Helena, TALASILA, Krishna M., MILETIC, Hrvoje, ATAI, Nadia A., BJERKVIG, Rolf, LAH TURNŠEK, Tamara. Cathepsin L silencing increases As2O3 toxicity in malignantly transformed pilocytic astrocytoma MPA58 cells by activating caspases 3/7. Experimental cell research, ISSN 0014-4827, 2017, vol. 356, 1,p 64-73, doi: 10.1016/j.yexcr.2017.04.013.

VITTORI, Miloš, BREZNIK, Barbara, HROVAT, Katja, KENIG, Saša, LAH TURNŠEK, Tamara. RECQ1 helicase silencing decreases the tumour growth rate of U87 glioblastoma cell xenografts in zebrafish embryos. Genes, ISSN 2073-4425, 2017, vol. 8, 9, p-11. http://www.mdpi.com/2073-4425/8/9/222, doi: 10.3390/genes8090222.

BREZNIK, Barbara, MOTALN, Helena, VITTORI, Miloš, ROTTER, Ana, LAH TURNŠEK, Tamara. Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines. Oncotarget, ISSN 1949-2553, 2017, 8, /15, p25482-25499, doi: 10.18632/oncotarget.16041.

MITROVIĆ, Ana, SOSIČ, Izidor, KOS, Špela, LAMPREHT TRATAR, Urša, BREZNIK, Barbara, KRANJC, Simona, MIRKOVIĆ, Bojana, GOBEC, Stanislav, LAH TURNŠEK, Tamara, ČEMAŽAR, Maja, SERŠA, Gregor, KOS, Janko. Addition of 2-(ethylamino)acetonitrile group to nitroxoline results in significantly improved anti-tumor activity in vitro and in vivo. Oncotarget, ISSN 1949-2553, 2017, 8/ 35, 59136-59147, , doi: 10.18632/oncotarget.19296.

2016

PODERGAJS, Neža, MOTALN, Helena, RAJČEVIĆ, Uroš, VERBOVŠEK, Urška, KORŠIČ, Marjan, OBAD, Nina, ESPEDAL, Heidi, VITTORI, Miloš, HEROLD-MENDE, Christel, MILETIC, Hrvoje, BJERKVIG, Rolf, LAH TURNŠEK, Tamara. Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells. Oncotarget, ISSN 1949-2553, 2016, vol. 7, no. 1, str. 593-609, ilustr., doi: 10.18632/oncotarget.5477.

VEČERIĆ-HALER, Željka, ERMAN, Andreja, CERAR, Anton, MOTALN, Helena, KOLOŠA, Katja, LAH TURNŠEK, Tamara, SODIN-ŠEMRL, Snežna, LAKOTA, Katja, MRAK POLJŠAK, Katjuša, ŠKRAJNAR, Špela, KRANJC, Simona, ARNOL, Miha, PERŠE, Martina. Improved protective effect of umbilical cord stem cell transplantation on cisplatin-induced kidney injury in mice pretreated with antithymocyte globulin. Stem Cells International (Online), ISSN 1687-9678, 2016,2016, pp 1-12, doi: 10.1155/2016/3585362.5

KOLOŠA, Katja, MOTALN, Helena, HEROLD-MENDE, Christel, KORŠIČ, Marjan, LAH TURNŠEK, Tamara. Paracrine effects of mesenchymal stem cells induce senescence and differentiation of glioblastoma stem-like cells. Cell transplantation, ISSN 0963-6897.2015, 24/4,pp 631-644, doi: 10.3727/096368915X687787. .

MOTALN, Helena, KOREN, Ana, GRUDEN, Kristina, RAMŠAK, Živa, SCHICHOR, Christian, LAH TURNŠEK, Tamara. Heterogeneous glioblastoma cell cross-talk promotes phenotype alterations and enhanced drug resistance. Oncotarget, ISSN 1949-2553, 2015, 6/ 38, p40998-41017, doi: 10.18632/oncotarget.5701.

HERMAN, Ana, GRUDEN, Kristina, BLEJEC, Andrej, PODPEČAN, Vid, MOTALN, Helena, ROŽMAN, Primož, HREN, Matjaž, ZUPANČIČ, Klemen, VEBER, Matija, VERBOVŠEK, Urška, LAH TURNŠEK, Tamara, PORČNIK, Andrej, KORŠIČ, Marjan, KNEŽEVIĆ, Miomir, JERAS, Matjaž. Analysis of glioblastoma patients' plasma revealed the presence of microRNAs with a prognostic impact on survival and those of viral origin. PloS one, ISSN 1932-6203, 2015,  10/5, p 1-20, ilustr., doi: 10.1371/journal.pone.0125791.