Department of Experimental Pharmacology

 

Table of contents:

1. Department history
2. Our staff
3. Research activities
4. Relevant grants
5. Major publications since 2010
6. Educational activity
7. Open positions

 

Department history

 

Our department is operating for over 60 years now. The first period of its history is linked to the Oncopathological Research Institute, founded by Hungarian Academy of Science member Béla Kellner back in 1954. From the 1970’s, following the fusion of the Research Institute and the National Institute of Oncology, it is functioning as a research department of the National Institute of Oncology. As a main activity, our department performs cancer therapy research and development, mainly based on animal experiments.

 The department has three Ph.D. researchers, two Ph.D. students, three M.Sc. students, and four technicians in scientific position, and six animal caretakers working with the laboratory animals.

 

 

 

Our staff:

 

Dr. József Tóvári, biologist,Ph.D., head of department

Dr. Dóra Türk, biologist, Ph.D.

Dr. Enikő Bálintné Tátrai, biologist, Ph.D.

Zita Hegedüs, biologist

Tamás Mihály Cserepes, biologist, Ph.D.student

Ildikó Kolarovszkiné Kovács, biologist

Ivan Randelovic, biologist, Ph.D. student

János Baliga, animal caretaker

Zoltán Bodrogi, animal caretaker

Irén Bodrogi-Mayer, research assistant

Anita Hidvégi, research assistant

Karola Stromajer, animal caretaker

Mónika Kovaljovné Hegedűs, research assistant

Edit Kovács, research assistant

Józsefné Szabó, animal caretaker

Anna Mária Tóth, research assistant

Erzsébet Várnai, animal caretaker

 

 

 

Research activities

 

The main scientific activities of the Department of the Experimental Pharmacology are focusing on tumor progression and metastasis. We investigate tumor cell migration, adhesion, interaction with extracellular matrices and the role of hypoxia in tumor aggressiveness in vitro and in vivo as well. Moreover, with the help of our collaborators we try to find new targets and mechanism for better treatment and study the therapy resistance against different modalities.

 

We run two major research projects at present. In the first we try to find the possible biological background of the resistance to anti-EGFR antibody therapy of head and neck squamous cell carcinomas. In the other project, in the frame of an international H2020 consortium (MAGICBULLET) we are testing different peptide-drug conjugates, synthesized by our partners, in different in vitro and in vivo tumor models.

 

In our Special Pathogen Free (SPF) animal house we developed and validated several subcutaneous and orthotopic murine and human tumor models for analyzing tumor growth and for detecting the effects of different therapies on tumor progression, neoangiogenesis and metastasis. In our cellular and molecular biology laboratory we have a human tumor cell culture collection from different tissue origin (melanoma, glioblastoma, head and neck, breast, colon, prostate, ovarian and lung cancers etc.) with different genetic background (EGFR, RAS, RAF, p53 etc. mutation or wild type, hormone receptor positivity). Using in vitro research techniques (PCR, gene sequencing, Western blot, flow cytometry, immunohistochemistry, confocal microscopy) we can analyze nucleic acid or protein expression or mutation status from different sample origins (cultured cells, paraffin or cryopreserved archived samples, tumor tissues from in vivo experiments).

 

In the SPF Animal House, we use C57Bl/6, BALB/c and DBA/2 inbred strains and BDF1 hybrid strain as immunocompetent animals for allograft experiments, and SCID (severe combined immune deficiency) mice for xenograft models.

 

 

 

 

Relevant grants:

 

1. H2020-MSCA-ITN-2019-861316 (2019-2022).

Peptide-Drug Conjugates for Targeted Delivery in Tumor Therapy „MAGICBULLET” 

 

2. NKFIH K116295 (2015-2019) 

Investigation of cetuximab resistance in head and neck squamous cell carcinomas.

 

3. NKFIH K119552 (2016-2020)

Development of bioconjugates for targeted tumor therapy of cancer types leading to high mortality 

 

4. NKFIH K124813 (2017-2021)

Signal transduction therapy in cancer and inflammation 

 

5. H2020, MSCA-ITN-2014-ETN 642004 (2015-2018)

Small Molecule Drug Conjugates for Targeted Delivery in Tumor Therapy “MAGICBULLET:Reloaded)

Principal Investigator: Dr. Norbert Sewald, University of Bielefeld

Senior coPI: Dr. József Tóvári

            www.magicbullet-reloaded.eu

 

 

 

Major publications from 2010:

 

 

Ranđelović I, Schuster S, Kapuvári B, Fossati G, Steinkühler C, Mező G, Tóvári J. Improved In Vivo Anti-Tumor and Anti-Metastatic Effect of GnRH-III-Daunorubicin Analogs on Colorectal and Breast Carcinoma Bearing Mice. 

Int J Mol Sci. 2019 Sep 25;20(19). pii: E4763. IF: 4.183.

 

Laszlo V, Valko Z, Ozsvar J, Kovacs I, Garay T, Hoda MA, Klikovits T, Stockhammer P, Aigner C, Gröger M, Klepetko W, Berger W, Grusch M, Tovari J, Waizenegger IC, Dome B, Hegedus B.  The FAK inhibitor BI 853520 inhibits spheroid formation and orthotopic tumor growth in malignant pleural mesothelioma.

J Mol Med (Berl). 2019, 97(2):231-242. IF: 4.746.

 

Kenessey I, Kramer Z, István L, Cserepes MT, Garay T, Hegedűs B, Dobos J, Tímár J, Tóvári J.  Inhibition of epidermal growth factor receptor improves antitumor efficacy of vemurafenib in BRAF-mutant human melanoma in preclinical model.

Melanoma Res. 2018, 28(6):536-546. IF: 3.135.

 

Laszlo V, Valko Z, Kovacs I, Ozsvar J, Hoda MA, Klikovits T, Lakatos D, Czirok A, Garay T, Stiglbauer A, Helbich TH, Gröger M, Tovari J, Klepetko W, Pirker C, Grusch M, Berger W, Hilberg F, Hegedus B, Dome B. Nintedanib is active in malignant pleural mesothelioma cell models and inhibits angiogenesis and tumor growth in vivo. Clin Cancer Res. 2018 Aug 1;24(15):3729-3740. IF: 10.199.

 

Füredi A, Szebényi K, Tóth Sz, Cserepes M, Hámori L, Nagy V, Karai E, Vajdovich P, Imre T, Szabó P, Szüts D, Tóvári J, Szakács G: Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer.

Journal of Controlled Release. 2017. 261: p. 287-296. IF: 7.786

 

Tátrai E, Bartal A, Gacs A, Paku S, Kenessey I, Garay T, Hegedűs B, Molnár E, Cserepes MT, Hegedűs Z, Kucsma N, Szakács G, Tóvári J. Cell type-dependent HIF1 α-mediated effects of hypoxia on proliferation, migration and metastatic potential of human tumor cells. Oncotarget. 2017 Jul 4;8(27): 44498-44510. IF: 5.168

 

Kenessey I, Kói K, Horváth O, Cserepes M, Molnár D, Izsák V, Dobos J, Hegedűs B, Tóvári J*, Tímár J*.: KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models.

Oncotarget. 2016 Nov 29;7(48):79503-79514. IF: 5.008.

 

Szebényi K, Füredi A, Kolacsek O, Csohány R, Prókai Á, Kis-Petik K, Szabó A, Bősze Z, Bender B, Tóvári J, Enyedi Á, Orbán TI, Apáti Á, Sarkadi B.: Visualization of Calcium Dynamics in Kidney Proximal Tubules.

J Am Soc Nephrol. 2015 Nov;26(11):2731-40. IF: 8.491

 

Szabo V, Bugyik E, Dezso K, Ecker N, Nagy P, Timar J, Tovari J, Laszlo V, Bridgeman VL, Wan E, Frentzas S, Vermeulen PB, Reynolds AR, Dome B, Paku S. Mechanism of tumour vascularization in experimental lung metastases.

J Pathol. 2015 Feb;235(3):384-96. IF: 7.381

 

Tóvári J, Futosi K, Bartal A, Tátrai E, Gacs A, Kenessey I, Paku S.

Boyden chamber-based method for characterizing the distribution of adhesions and cytoskeletal structure in HT1080 fibrosarcoma cells.

Cell Adh Migr. 2014 Sep 3;8(5):509-16. doi: 10.4161/cam.28734. Epub 2014 Oct 31. IF: 4.505

 

Rózsás A, Berta J, Rojkó L, Horváth LZ, Keszthelyi M, Kenessey I, László V, Berger W, Grusch M, Hoda MA, Török S, Klepetko W, Rényi-Vámos F, Hegedűs B, Döme B, Tóvári J.

Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma. 

PLoS One. 2013 Oct 14;8(10):e77459. IF: 2.606

 

Szabó B, Nelhűbel GA, Kárpáti A, Kenessey I, Jóri B, Székely Cs, Peták I, Lotz G, Hegedűs Z, Hegedűs B, Füle T, Döme B, Tímár J, Tóvári J. Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. 

ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B 47:(6) pp. 487-496. (2011). IF: 2.857 

 

Manea M, Leurs U, Orban E, Baranyai Z, Ohlschlager P, Marquardt A, Schulcz A, Tejeda M, Kapuvari B, Tovari J, Mezo G. Enhanced Enzymatic Stability and Antitumor Activity of Daunorubicin-GnRH-III Bioconjugates Modified in Position 4. BIOCONJUGATE CHEMISTRY 22:(7) pp. 1320-1329. (2011). IF: 4.930 

 

Kenessey I, Keszthelyi M, Kramer ZF, Berta J, Adam A, Dobos J, Mildner M, Flachner B, Cseh S, Barna G, Szokol B, Orfi L, Keri G, Dome B, Klepetko W, Timar JZ, Tóvári J

Inhibition of c-Met with the Specific Small Molecule Tyrosine Kinase Inhibitor SU11274 Decreases Growth and Metastasis Formation of Experimental Human Melanoma.

CURRENT CANCER DRUG TARGETS 10:(3) pp. 332-342. (2010). IF: 4.771 

 

 

 

 

Full list of publications of the Department

 

 

Educational activity:

 

Dr. József Tóvári is a supervisor at the Doctoral School of Pathological Sciences at Semmelweis University, and at the Doctoral School of the Clinical Medicine Science at University of Pécs.

 

Under his supervision the following students took the Ph. D. degree:

 

Dr. Bíborka Bereczky (co-supervisor: Prof. József Tímár): Analysis of certain aspects of hematogenous and lymphogenous dissemination in preclinical models. 2010.

 

Dr. István Kenessey: The role of the motogenic signal in human melanoma cells. 2010.

 

Dr. Balázs Szabó: Studying EGFR-receptor and claudin expression patterns in head and neck squamous cell carcinomas. 2014.

 

Dr. Anita Rózsás (co-supervisor: Dr. Balázs Döme): New prognostic markers in lung adenocarcinoma. 2016.

 

The following students under his supervision are candidates for the Ph.D. degree:

Mihály Tamás Cserepes, Ivan Ranđelović.

 

Dr. József Tóvári holds courses at the Semmelweis University, at the University of veterinary Medicine and at the Eötvös Loránd University on tumour biology, biotechnology, nanomedicine and tumour progression.

 

 

1. Open position

 

Investigation of the effect of newly synthesized compounds on tumor cell proliferation in vitro and on tumor growth and metastasis in vivo 

 

The PhD project will focus on the investigation of anti-tumoral effects of selected molecules in different in vitro and in vivo experimental models. Potential anti-metastatic effects of the molecules will be studied in in vitro migration and invasion assays as well. The compounds of interest, synthesized and tested by other members of our consortium, will be investigated in different toxicology models. Subcutaneous tumor and orthotopically transplanted metastasis as well as patient-derived tumor xenografts (PDTX) mice models will be used for in vivo treatment efficacy evaluation studies. More

 

Detailed information: https://www.uni-bielefeld.de/chemie/oc3sewald/magicbullet-reloaded/positions.html

Please send application to magicbullet@uni-bielefeld.de.