Personnel

https://www.onko-i.si/fileadmin/onko/datoteke/dokumenti/043802-stocco.pdfUnit of Radiation Oncology
Prof. Gregor Serša, PhD (Biol.); Head
T: +386 1 5879 434
F: +386 1 5879 434
E: gsersa@onko-i.si
C.V.

Simona Kranjc, PhD (Biol.)
T: +386 1 5879 545
F: +386 1 5879 434
E: skranjc@onko-i.si  

Suzana Mesojednik, BSc (Biol.) 
T: +386 1 5879 545
F: +386 1 5879 434
E: smesojednik@onko-i.si  

Urška Kamenšek
T: +386 1 5879 536
F: +386 1 5879 434
E: ukamensek@onko-i.si

Unit of Radiation Oncology employs four health care associates and a laboratory technician.

Unit of Tumor Biotherapy
Assist.Prof. Maja Čemažar, PhD (Biol.); Head
T: +386 1 5879 544
F: +386 1 5879 434
E: mcemazar@onko-i.si

Unit of Tumor Biotherapy employs two health care associates and a laboratory technician.

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Scientific Research

In recent years, scientific research of the Department has been extended into the domain of biomedical applications of electroporation. The research on electroporation as a drug delivery system that increases the in-vivo administration of cytostatics into tumors, known as electrochemotherapy (gif, 14.99 Kb), will shortly be completed.


As a result of joint research work with the Laboratory of Biocybernetics (Head Prof. Miklavčič), this treatment method has been already applied in clinical practice. The development of this method, from the very first preclinical trials to the investigations of mechanisms and application in clinical practice in the treatment of skin tumors, has been supported by European project ESOPE which was completed in 2006. The aim of this project was to elaborate, in cooperation with different partners from Europe, standard operating procedures (SOP) for the treatment with electrochemotherapy. The project was successfully accomplished; the drug used in this treatment modality is cisplatin which is in the process of registration for the application in electrochemotherapy.


Furthermore, the laboratory investigates also other biomedical applications of electroporation, e.g. the exploitation of modulation of tumor blood perfusion and of its oxygenization in combination with different treatment modalities. Among the investigated combinations, the most advantageous were the combination with bioreductive drug tirapazamine, a selectively toxic agent at low oxygen concentration, and the combination with hyperthermia that works on the same principle.


Unit of Radiation Oncology focused its research on potentiation of radiosensibilitizing cytostatics with electroporation. The results  (gif, 18.35 Kb) are most promising as the radiosensibilitizing effect of cisplatin and bleomycin increases the factors 1.7 and 1.9 by using electroporation. These studies are of invaluable importance because the electroporation and electrochemotherapy in combination with radiotherapy have become a generally used treatment method in clinical practice.

Electroporation may also be used to administer naked DNA in in vivo tumors; this is the so-called electrogene therapy. This is another new promising research domain of the Unit of Tumor Biotherapy. So far, investigations have been conducted on the optimization of electric parameters, modulation of extracellular matrix to improve cell transfection in tumors and muscles.. At present, reporter genes are used (the research with therapeutic genes (gif, 28.95 Kb))  and the research with therapeutic genes is also under way. In-depth investigations of electrogene therapy with tumor suppressor gene p53 proved an increased efficiency of this therapy which may yield complete recovery if performed at least in 3 successive sessions with a two-day interval between each session. With a combination of electrogene therapy with tumor suppressor gene p53 and of electrochemotherapy with cisplatin, the complete recovery may be obtained in some tumors already after the first application. The most recent researches are focused mainly on electroimmunotherapy with interleukin that has a direct cytologyical effect on tumor cells and on better stimulation of immune response of an organism.

Teaching

The personnel of the Department of Experimental Oncology are participating as lecturers in undergraduate and postgraduate courses.

Undergraduate courses are held at the University College of Health Studies of the University of Ljubljana, at the University College of Health Studies in Isola at the University of Primorska, and at the School of Environmental Sciences Nova Gorica, Nova Gorica Polytechnics, whereas postgradutae courses are given to the students of biomedicine, biotechnics, and medical physics at the University of Ljubljana.

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Research Projects

Development and Evaluation of New Approaches to Cancer Treatment
Principal investigator: Prof. Gregor Serša, PhD (Biol.)
Code: P3-0003
Financed by: Ministry of Higher Education, Science and Technology RS (2004–2008)

Treatment of Malignant Tumors with Electrogene Therapy
Principal investigator: Assist. Prof. Maja Čemažara, PhD (Biol.)
Code: J3-7044
Financed by: Slovenian Research Agency (2005–2008)


ESOPE: European Standard Operating Procedures for Electrochemotherapy and Electrogenetherapy
Project co-ordinator: Dr. Lluis M. Mir, Institute Gustave-Roussy, Villejuif, France
Partner from Slovenia: Prof. Gregor Serša, PhD (Biol.)
Code: QLRT-2001-02003
Financed by: European Commission, Brussels, Belgium (2002–2005)

New Theoretical Models of Cell and Tissue Electropermeabilization, their Experimental Validation and Technological Applications (2005–2007)
French-Slovenian joint scientific cooperation (Project PICS)
Partners from France: dr. Lluis M. Mir, Institut Gustave-Roussy, Villejuif
Prof. Justin Teissié, Institut de Pharmacologie et de Biologie Structurale, Toulouse
Partners from Slovenia: Prof. Damijan Miklavčič, Faculty of Electrotechnics, University of Ljubljana; Prof. Gregor Serša, Institute of Oncology Ljubljana
Financed by: Centre National de Recherche Scientific (CNRS), France; Ministry of Higher Education, Science and Technology, RS

ANGIOSKIN: DNA Electrotransfer of Plasmids Coding for Antiangiogenic Factors as a Proof of Principle of Non-Viral Gene Therapy for the Treatment of Skin Disease (2005-2008) Project co-ordinator: Dr. Lluis M. Mir, Institute Gustave-Roussy, Villejuif, France Partner from Slovenia: Prof. Damijan Miklavcic, Faculty of Electrical Eng., University of Ljubljana and Prof. Gregor Serša as subcontractor Other partners: Dr. Ruggero Cadossi, IGEA S.r.l., Modena, Italy, Prof. Michel Marty, Institute Gustave-Roussy, Villejuif, France, Prof. Véronique Préat, Catholic University of Louvain, Brussels, Belgium, Dr. Julie Gehl, Herlev Hospital, Denska, Prof. Michael P. Schön, University of Würzburg, Nemčija, Dr. Dominique Constantini, BioAlliance Pharma SA, Paris, France, Dr. Lone Skov, Gentofte Hospital, Hellerup, Denmark Financed by: European Commission, Brussels, Belgium Code: LSHB-CT-2005-512127 Partnership in science project No. 3/2006 “Therapeutic Targeting of Tumor Vasculature with Antiangiogenic Gene Therapy” (2006) Partner from U.K.: Chryso Kanthou, PhD, University of Sheffield Partner from Slovenia: Maja Čemažar, PhD, Institute of Oncology Financed by: British Council and ARRS CONTICANET: CONnective TIssue Cancers NETwork to integrate European Experience in Adult and Children (2006-2008) Partner from Slovenia: Prof.. Zvonimir Rudolf, MD, PhD, Institute of Oncology Ljubljana Financed by: European Commission, Brussels, Belgium Code: FP6-018806

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Major Publications

  • Serša G, Kranjc S, Čemažar M. Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys 2000; 46: 1037–41.
  • Serša G, Kržič M, Šentjurc M, Ivanuša T, Beravs K, Čemazar M, Auersperg M, Swartz HM. Reduced tumor oxygenation by treatment with vinblastine. Cancer Res 2001; 61: 4266–4271.
  • Čemažar M, Serša G, Wilson J, Tozer GM, Hart SL, Grošel A, Dachs G. Effective gene transfer to solid tumours using different non-viral gene delivery techniques: electroporation, liposomes and integrin-targeted vector. Cancer Gene Ther 2002; 9: 399–406.
  • Serša G, Čemažar M, Rudolf Z. Electrochemotherapy: advantages and drawbacks in treatment of cancer patients (review article) Cancer Therapy 2003; 1: 133–42.
  • Čemažar M, Wilsom I, Dachs GU, Tozer G, Serša G. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution. BMC Cancer 2004; 4: 81. doi: 10.1186/1471-2407-4-81.
  • Snoj M, Rudolf Z, Čemažar M, Jančar B, Serša G. Successful sphincter-saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anti-Cancer Drugs 2005; 16(3):345-8.
  • Tozon N, Kodre V, Serša G, Čemažar M. Effective treatment of perianal tumours in dogs with electrochemotherapy. Anticancer Res 2005; 25: 839-846.
  • Čemažar M, Wilson I, Prise VE, Bell KM, Hill SA, Tozer GM. The endothelin B (ETB) receptor agonist IRL 1620 is highly vasoconstrictive in two syngeneic rat tumour lines: potential for selective tumour blood flow modification. Brit J Cancer 2005; 93: 98-106.
  • Grabner S, Modec B, Čemažar M, Bukovec N. Crystal structures and cytotoxicity of isopropylamine Pt(II) complexes: a trinuclear squarato-bridges [Pt3(2-C4O4)3(H2NPri)6]x3H2O and a mononuclear cis-[Pt(NO3)2(H2NPri)2]. J Inorg Biochem 2005; 99:1465-71.
  • Kranjc S, Čemažar M, Grošel A, Šentjurc M, Serša G. Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice. BMC Cancer. 2005; 5: 115.
  • Čemažar M, Golzio M, Rols MP, Serša G, Teissie J. Electrically-assisted nucleic acid delivery in vivo: Where do we stand? Review. Current Pharmaceutical Design 2006; 12: 3817-3825.
  • Čemazar M, Pipan Z, Grabner S, Bukovec N, Serša G. Cytotoxicity of Different Platinum (II) Analogues to Human Tumour Cell Lines In Vitro and Murine Tumour In Vivo Alone or Combined with Electroporation. Anticancer Res 2006; 3: 1997-2002.
  • Čemažar M, Golzio M, Escoffre JM, Couderc B, Serša G, Teissie J. In vivo imaging of tumour growth after electrochemotherapy with cisplatin. Biochem, Biophys Res Commun, 2006, 348: 997-1002.
  • Grabner S, Čemažar M, Bukovec N, Serša G. Syntheses and cytotoxicity of Pt(II) complexes with Acyclovir. Acta Chim Slov 2006; 51: 153-6.
  • Pavlin D, Tozon N, Serša G, Pogačnik A, Čemažar M. Electrogene therapy in cancer treatment. Slov Vet Res 2006; 43: 77-84.
  • Serša G, Čemažar M, Miklavčič D, Rudolf Z. Electrochemotherapy of tumours. Radiol Oncol 2006; 40: 163-74.
  • Snoj M, Rudolf Z, Paulin-Košir S, Čemažar M, Snoj R, Serša G. Long lasting complete response in melanoma treated by electrochemotherapy. EJC Suppl 2006; 4: 26-8.
  • Serša G. The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical uses. EJC Suppl 2006; 4: 52-9.
  • Mir L M, Gehl J, Serša G, Collins CG, Garbay JR, Billard V, Geertsen P, Rudolf Z, O’Sullivan GC, Marty M. Standard Operating Procedures of the Electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by Cliniporator ™ by means of invasive or non-invasive electrodes. EJC Suppl 2006; 4: 14-25.
  • Marty M, SERŠA G, Garbay JR, Gehl J, Collins CG, Snoj M, Billard V, Geertsen PF, Larkin JO, Miklavčič D, Pavlović I, Paulin-Kosir SM, Čemažar M, Morsli N, Soden DM, Rudolf Z, Robert C, O’Sullivan GC, Mir LM. Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl 2006; 4: 3-13.
  • Kanthou C, Kranjc S, Serša G, Tozer GM, Zupanic A, Čemažar M. The endothelial cytoskeleton as a target of electroporation based therapies. Molecular Cancer Therapeutics, in press.
  • Grošel A, Serša G, Kranjc S, Čemažar M. Electrogene therapy with p53 of murine sarcomas alone or combined with electrochemotherapy using cisplatin. DNA Cell Biol 2006, in press.

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