We have developed a new cell-based biosensor system that provides rapid and simple detection of genotoxic substances that is based on stable transfection of human hepatoma HepG2 cells with a plasmid that encodes the red fluorescent protein DsRed2 under the control of the CDKN1A promoter (HepG2CD-KN1A–DsRedcells) (patented in 2012). In this study the assay was evaluated by testing direct and indirect activity of genotoxic compounds with different mechanisms of action, along with non-genotoxic compounds. Out of 25 compounds that are known to be genotoxic in vitro and in vivo, 21(84%) are detected as positive at non-cytotoxic doses, whereas of 12 compounds not considered genotoxic, 11 (92%) are negative. These data indicate the high sensitivity and specificity of our biosensor system. Based on its simplicity and sensitivity this biosensor has the potential to become a valuable tool for genotoxicity screening for chemical safety evaluation and in environmental genotoxicity screening.
F.08 Development and manufacture of a prototype
COBISS.SI-ID: 1771131Metka Filipič was the coordinator of EUFP7 CytoThreat. The aim of the project was to explore whether residues of cytostatic drugs in the aquatic environment represent risk for environment and human health. .In the frame of the project we developed analytical methods for detection of residues of cytostatics and their degradation products in the environment that were not available at the time and enabled their determination in aquatic environment. With ecotoxicological studies tht were in an innovative manner coupled with detection of genotoxic effects and analyses of gene expression in aquatic organisms and cells in vitro we were the first hwo demonstrated that the residues of certain cytostatics induce adverse effect at concentrations relevant for environment. Nine partners from six countries were collaborating in this project. The total value of the project was 3.3 MIO EUR. For the successful coordination and finalization of the project dr. Metka Filipič received in 2016 national Zois award for important achievements in the field of the studies of environmental pollutants and their adverse effects on environmental and human health.
D.06 Final report on a foreign/international project
COBISS.SI-ID: 3647055Antibody drug conjugates (ADCs) are promising biological therapeutics against various cancers. In the subgroup of HER2 positive breast carcinoma (BCa), the patients have been shown to benefit from the treatment by a HER2 monoclonal antibody, transtuzumab conjugated with toxic microtubulin inhibitor mayatansinoid, the ADC, named Kadcyla. Due to its complex activity an ADC needs to be carefully designed for its optimal performance. The aim of our study was to establish reliable in vitro models to evaluate the characteristics of Kadcyla in order and utilize findings for further improvement of this biological drug therapy of most resistant breast carcinoma cells. We prepared 3D spheroids of mono- and multicellular co-culture models wih HUVEC and BCa: MCF10A spheroids. In conclusion, different resistance to cytotoxic drugs was observed between the treated types of mono- and mixed multicellular spheroids,implying that stromal component of the tumor microenvironment indeed plays crucial role in tumor resistance to therapy.
F.07 Improvements to an existing product
COBISS.SI-ID: 4316495In May 2017, we organized the international "8th Conference on Experimental and Translational Oncology-CETO", which we conveyed under the auspices of the Society of Radiology and Oncology and took place in Portorož. Let us underline, that this was the recent in the series of international conferences, organised by the same group. This year, the organization of the CETO conference was entrusted to our Department headed by Tamara Lah, but most of the members of the group participated in the organization. The lectures and presentations were attended by numerous domestic and foreign top researchers, including a Nobel Prize winner, doctors and clinical oncologists and surgeons. This Conferences are also intended for the education of doctoral students and young researchers who are only entering the field of this research and, of course, their international exchanges and networking in the desire to increase internationalization of the field.
B.02 Presiding over the programming board of a conference
COBISS.SI-ID: 289740544Chemicals Office of the Republic of Slovenia, Ministry of Health has granted the Department of Genetic Toxicology and Cancer biology the Statement of compliance for performing the mutagenicity studies in compliance with OECD Principles of Good Laboratory Practice (GLP) on the 13th of July 2015 and in 2017 its prolongation for another 2 years. Our GLP services are offered for non-clinical health and environmental safety studies required by regulations for the purpose of registering or licensing pharmaceuticals, pesticides, food and feed additives, cosmetic products, veterinary drug products and similar products, and for the regulation of industrial chemicals. In Slovenia, this is the only GLP laboratory for these services, which is of particular importance for Slovenian companies developing and producing new products in the fields of pharmacy, cosmetics, food and plant protection products.
D.02 Establishment of a research centre, laboratory, study course, association