Biochemistry of molecular carcinogenesis and enzymes of malignant transformation
Research
Metabolism of xenobiotics
- Effect of biotransformation on biochemical and pharmacological aspects of drugs
- Metabolic activation and detoxication of carcinogenic compounds
- Role of cytochrome P450 system and other biotransformation enzymes in metabolism of xenobiotics
Nanoforms of drugs
- Preparation and characterisation of anticancer drugs in form nanoparticles
- Preparation of specific-targeted nanoparticles
- Effects of drug nanoforms on cancer cells in vitro and in vivo
Tyrosine kinase inhibitors (TKIs)
- Study of metabolism of TKIs by enzymes of 1. and 2. phase of biotransformation
- Effect of TKIs on expression of biotransformation enzymes
- Effect of TKIs on cancer cells in vitro and in vivo
Solved grants
Finished grants
GA ČR 18-10251S (2018–2020)
Comprehensive insight into mechanisms of action and metabolism of
tyrosine kinase inhibitors and a study of ways increasing their antitumor efficiency
GA ČR 17-12816S (2017–2019)
Construction of modified apoferritin nanocarriers bearing anticancer drugs and study of
mechanisms enhancing their efficiency in anticancer therapy
GAUK 998217 (2017–2019)
The mechanism of action of doxorubicin and ellipticine encapsulated in apoferritin nanotransporters on tumor cells – in vitro study
AZV 15-28334A
Vliv metalothioneinů na vazbu platinových cytostatik na DNA v nádorových buňkách
GA ČR 18-10251S (2016–2018)
Studium metabolismu sarkosinu a jeho participace na vývoji nádorů prostaty
GA ČR P303/12/G163 (2012–2018)
Centrum interakcí potravních doplňků s léčivy a nutraceutiky
GA ČR 15-19883S (2015–2017)
Mechanismus intraproteinového/mezidoménového přenosu signálu u modelových hemových senzorových proteinů
GA ČR 14-18344S (2014–2016)
Vývoj částic obsahujících cytostatika a enzymy pro zlepšení chemoterapie lidských neuroblastomů a studium mechanismu jejich působení
GA ČR P301/10/0356 (2010–2014)
Studie participace specifických mechanismů poškození DNA na cytoxicitě cytostatik vůči lidským chemosensitivním a chemorestentním neuroblastomům
GA ČR P503/10/0408 (2010–2013)
Studium mechanismu degradace 17alfa-ethynylestradiolu pomocí enzymů lignolytických hub
GA ČR 303/09/472 (2009–2013)
Studium participace biotransformačních enzymů na vývoji ledvinného selhání a nádorů močových cest vyvolaných aristolochovou kyselinou
GA ČR P503/11/163 (2011–2013)
Enzymy a mechanismy mikrobní degradace nitroaromatických sloučenin.
UNCE 204025/2012 (2012–2017)
Moderní technologie pro identifikaci a optimalizaci nádorových léčiv nové generace
Selected papers (5 years)
Bárta F, Dedíková A, Bebová M, Dušková Š, Mráz J, Schmeiser HH, Arlt VM, Hodek P, Stiborová M: Co-exposure to aristolochic acids I and II increases DNA adduct formation resposible for aristolochic acid I-mediated carcinogenicity in rats. International Journal of Molecular Sciences, 22(19), 10479, 2021
Dračínská H, Indra R, Jelínková S, Černá V, Arlt VM, Stiborová M: Benzo[a]pyrene-induced genotoxicity in rats is affected by co-exposure to sudan I by altering the expression of biotransformation enzymes. International Journal of Molecular Sciences, 22(15), 8062, 2021
Jáklová K, Feglarová T, Rex S, Heger Z, Eckschlager T, Hraběta J, Hodek P, Kolárik M, Indra R: Apoferritin/vandetanib association is long-term stable but does not improve pharmacological properties of vandetanib. International Journal of Molecular Sciences, 22(8), 4250, 2021
Dedíková A, Bárta F, Martínek V, Kotalík K, Dušková Š, Mráz J, Arlt VM, Stiborová M, Hodek P: In vivo metabolism of aristolochic acid I and II in rats is influenced by their coexposure. Chemical research in toxicology, 33(11), 2804-2818, 2020
Indra R, Vavrová K, Pompach P, Heger Z, Hodek P: Identification of enzymes oxidizing the tyrosine kinase inhibitor cabozantinib: Cabozantinib is predominantly oxidized by CYP3A4 and its oxidation is stimulated by cyt b5 activity. Biomedicines, 8(12), 547 (2020)
Indra R, Pompach P, Vavrova K, Jaklova K, Heger Z, Adam V, Eckschlager T, Kopeckova K, Arlt VM, Stiborova M: Cytochrome P450 and flavin-containing monooxygenase enzymes are resposible for differential oxidation of anti-thyroid-cancer drug vandetanib by human and rat hepatic microsomal systems. Environmental Toxicology and Pharmacology, 74:, (2020).
Strmiska V, Michalek P, Eckschlager T, Stiborova M, Adam V, Krizkova S, Heger Z: Prostate cancer-specific hallmarks of amino acids metabolism: Towards a paradigm of precision medicine. Biochimica et Biophysica Acta – Reviews on Cancer, 1871(2), 248-258, (2019).
Sborchia M, De Prez EG, Antoine MH, Bienfait L, Indra R, Valbuena G, Phillips DH, Nortier JL, Stiborova M, Keun H, Arlt VM: The impact of p53 on AAI-induced nephrotoxicity and DNA damage in vivo and in vitro. Archives of Toxicology, 93(11): 3345-3366, (2019).
Indra R, Pompach P, Martinek V, Takacsova P, Vavrova K, Heger Z, Adam V, Eckschlager T, Kopeckova K, Arlt VM, Stiborova M: Identification of human enzymes oxidizing anti-thyroid-cancer drug vandetanib and explanation of the high efficiency of cytochrome P450 3A4 in the oxidative reaction. International Journal of Molecular Sciences, 20(14): 3392, (2019).
Indra R, Cerna T, Heger Z, Hrabeta J, Wilhelm M, Dostalova S, Lengalova A, Martinkova M, Adam V, Eckschlager T, Schmeiser HH, Arlt VM, Stiborova M: Ellipticine-loaded apoferritin nanocarrier retains DNA adduct-based cytochrome P450-facilitated toxicity in neuroblastoma cells. Toxicology, 419: 40, (2019).
Reed L, Indra R, Mrizova I, Moserova M, Schmeiser HH, Wolf CR, Henderson CJ, Stiborova M, Phillips DH, Arlt VM: Application of hepatic cytochrome b5/P450 reductase null (HBRN) mice to study the role of cytochrome b5 in the cytochrome P450-mediated bioactivation of the anticancer drug ellipticine. Toxicology and Applied Pharmacology. 366: 64-74, (2019).
Krizkova S, Kepinska M, Emri G, Eckschlager T, Stiborova M, Pokorna P, Heger Z, Adam V. An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena. Pharmacology and Therapeutics .183: 90–117, (2018)
Reed L, Mrizova I, Barta F, Indra R, Moserova M, Kopka K, Schmeiser HH, Wolf CR, Henderson CJ, Stiborova M, Phillips DH, Arlt VM. Cytochrome b5 impacts on cytochrome P450-mediated metabolism of benzo[a]pyrene and its DNA adduct formation: studies in hepatic cytochrome b5/P450 reductase null (HBRN) mice. Archives of Toxicology. 92(4): 1625-1638, (2018).
Stiborova M, Dracinska H, Borek-Dohalska L, Klusonova Z, Holecova J, Martinkova M, Schmeiser HH, Arlt VM: Exposure to endocrine disruptors 17alpha-ethinylestradiol and estradiol influences cytochrome P450 1A1-mediated genotoxicity of benzo[a]pyrene and expression of this enzyme in rats. Toxicology, 400: 48-56, (2018).
Eckschlager T, Plch J, Stiborova M, Hrabeta J: Histone deacetylase inhibitors as anticancer drugs. International journal of molecular sciences, 18(7): 1414, (2017).
Dostalova S, Cerna T, Hynek D, Koudelka Z, Vaculovic T, Kopel P, Hrabeta J, Heger Z, Vaculovicova M, Eckschlager T, Stiborova M, Adam V: Site-Directed Conjugation of Antibodies to Apoferritin nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells. ACS Applied Materials and Interfaces. 8(23): 14430-14441, (2016).
Stiborova M, Arlt VM, Schmeiser HH: Balkan endemic nephropathy: an update on its aetiology. Archives of toxicology, 90(11): 2595-2615, (2016).
Krais AM, Speksnijder EN, Melis JPM, Indra R, Moserová M, Godschalk RW, van Schooten FJ, Seidel A, Kopka K, Schmeiser HH, Stiborová M, Phillips DH, Luijten M, Arlt VM: The impact of p53 on DNA damage and metabolic activation of the environmental carcinogen benzo[a]pyrene: effects in Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice. Archives of Toxicology, 90(4): 839-851, (2016).
Dracinska H, Barta F, Levova K, Hudecova A, Moserova M, Schmeiser HH, Kopka K, Frei E, Arlt VM, Stiborova M: Induction of cytochromes P450 1A1 and 1A2 supresses formation of DNA adducts by carcinogenic aristolochic acid I in rats in vivo. Toxicology. 344: 7-18, (2016).
Cooperation
Mendel University in Brno, Institute of Chemistry and Biochemistry (Brno, Czech Republic)
King’s College London, Department of Analytical, Environmental & Forensic Sciences (London, UK)
Institute of Toxicology and Chemotherapy, German Cancer Research Centre (Heidelberg, Germany)
Université Libre de Bruxelles, Nephrology Department (Brussel, Belgium)
People
Head of group
Group members
PhD students
Katarína Vavrová
Alena Dedíková
Teaching (Katedra biochemie, PřF UK)
Subjects
MC250P03B – Biochemie II
MC250P40B – Biochemie II (kata)
MC250P24 – Xenobiochemie
MC250P01A – Enzymologie
MO550P88 – Biochemie pro ŽP
MC250P50 – Management biochemie
MC250C01 – Praktikum z laboratorní techniky biochemie
MC250C01N – Praktikum z laboratorní techniky biochemie pro KATA
MC250C24 – Cvičení z biochemie pro biochemiky
MC250P63 – Molekulární onkologie
Thesis
Contact
Department of Biochemistry, room 221 (1. floor)
Faculty of Science, Charles University
Hlavova 2030/8, 128 43 Prague 2
tel: +420 221 951 285
e-mail: radek.indra(at)natur.cuni.cz
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