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DEPARTMENT OF CELL BIOLOGY. Head: Dr. Jacek Bigda, Associate Professor. Research Staff: Dr. Małgorzata Doszczak Dr. Patrycja Koszałka Dr. Zuzanna Dobrzańska. Ph.D. Students: Marcin Okrój Arkadiusz Pierzchalski. MAIN TOPIC. Mechanism of action of
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DEPARTMENT OF CELL BIOLOGY Head:Dr. Jacek Bigda, Associate Professor Research Staff: Dr. Małgorzata Doszczak Dr. Patrycja Koszałka Dr. Zuzanna Dobrzańska Ph.D. Students: Marcin Okrój Arkadiusz Pierzchalski
MAIN TOPIC Mechanism of action of tumor necrosis factor (TNF) in vitro & in vivo TEACHING cell biology, histology, immunology
DEPARTMENT OF CELL BIOLOGYresearch interests: • mechanism of IL-1-induced cytotoxicity; • intracellular signaling of tumor necrosis factor; • mechanism of toxicity of theanti-angiogenic fumagillin derivative, TNP-470; • mechanism of anti-tumor action of poly-RGD peptides; • mechanism of accelerated growth of hamster melanoma following LPS application.
m m N N N N N N T T T T T T F F F F F F U 937 – human histiocytic lymphoma TNF-R55 TNF-R75 Response
Cycloheximide(CHX) U937 cell variants
U 937G U 937ATCC U 937M
140 120 100 80 Cell viabiltiy (%) 60 40 20 0 1 2 3 4 10 10 10 10 10 0 IL-1 (U/ml) IL-1/CHX IL-1/CHX/pAb anty-TNF 140 120 100 80 Cell viability (%) 60 40 20 10 0 10 1 10 2 10 3 10 4 0 IL-1/CHX IL-1/CHX/mAb anty-TNF IL-1 (U/ml) IL-1 cytotoxicity
120 100 120 80 100 80 60 Cell viability (%) 60 40 Cell viability (%) 40 20 20 0 0 4 0 1:4 1:2 1:1 1 0 1:8 1:4 1:2 1 supernatant dilution supernatant dilution sup IL-1/CHX sup IL-1/CHX + pAb anty-TNF sup IL-1/CHX sup IL-1 sup kontr. sup CHX IL-1 cytotoxicity
IL-1 cytotoxicity 500 control control 400 0,5 h CHX 1 h IL-1 2 h 300 4 h TNF [pg/ml] IL-1/CHX 200 100 0
Isotype control Untreated IL-1/CHX
DEPARTMENT OF CELL BIOLOGYfinancial support: • Analysis of mechanism regulating secretion of TNF following application of interleukin 1 and cycloheximide; State Committee for Scientific Research, Poland (2002-2005); • Mechanism of synergistic anti-tumor action of tumor necrosis factor (TNF) and angiogenesis inhibitor TNP-470; State Committee for Scientific Research, Poland (2001-2004); • Analysis of TNF sensitivity of variants of the U937 cell line; Intramural grant, Medical University of Gdańsk (2002-2003); • Modulation of tumor growth by means of cytokines; Core fund, Intercollegiate Faculty of Biotechnology UG-MUG;
DEPARTMENT OF CELL BIOLOGYselected previous grants: • Significance of tumor necrosis factor and its receptors for growth and dissemination of Bomirski melanoma; State Committee for Scientific Research, Poland (1994-1997); • Immunomodulatory and anti-tumor activity of cloned and purified rat tumor necrosis factor; State Committee for Scientific Research, Poland(1997-2000); • Influence of receptors of tumor necrosis factor for apoptosis of cancer cells; State Committee for Scientific Research, Poland (1997-2000); • Mechanism of cytotoxic action of interleukin 1; State Committee for Scientific Research, Poland (1999-2002); • TNF gene polymorphism and humoral reactivity against p53 protein in patients suffering from non-small cell lung cancer; State Committee for Scientific Research, Poland(1999-2002).
Tri-City Central Animal Laboratory, Medical University of Gdańsk
Tri-CityCentral Animal Laboratory, Medical University of Gdańsk