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DEPARTMENT OF CELL BIOLOGYDEPARTMENT 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 TOPICMAIN TOPIC
Mechanism of action of tumor necrosis factor (TNF)
in vitro & in vivo
TEACHINGTEACHING
cell biology, histology, immunology
DEPARTMENT OF CELL BIOLOGYDEPARTMENT OF CELL BIOLOGYresearch interestsresearch interests::
mechanism of IL-1-induced cytotoxicity;
intracellular signaling of tumor necrosis factor;
mechanism of toxicity of the anti-angiogenic fumagillin derivative, TNP-470;
mechanism of anti-tumor action of poly-RGD peptides;
mechanism of accelerated growth of hamster melanoma following LPS application.
U 937U 937 – – human histiocytic lymphomahuman histiocytic lymphoma
TNF-R55
F
N
TF
N
T F
N
T
TNF-R75
F
N
T
m
F
N
T
m
F
N
T
0
20
40
60
80
100
120
0 0,1 1 10 100 1000TNF (U/mL)
Żyw
otn
ość
kom
óre
k (
%)
U937 ATCC U937 M U937 G
Cycloheximide (CHX)
0
20
40
60
80
100
120
0 1 10 100 1000TNF (U/mL)
Żyw
otn
ość
ko
mó
rek (
%)
U937 ATCC U937 M U937 G
U937 cell variantsU937 cell variants
U 937MU 937G U 937ATCC
0
20
40
60
80
100
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Żyw
otn
ość
ko
móre
k (
%)
mTNF Kontrola
0
20
40
60
80
100
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Ży
wo
tno
ść k
om
óre
k (
%)
mTNF Kontrola
0
20
40
60
80
100
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Ży
wotn
ość
kom
óre
k (
%)
mTNF Kontrola
0
20
40
60
80
100
120
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Żyw
otn
ość
ko
mó
rek
(%)
Kontrola m/sTNF + CHX mTNF + CHX
0
20
40
60
80
100
120
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Żyw
otn
ość
ko
mó
rek
(%)
Kontrola m/sTNF + CHX mTNF + CHX
0
20
40
60
80
100
120
140
1,25 2,5 5
I lość mTNF (tys. komórek CHO)
Żyw
otn
ość
ko
mó
rek
(%)
Kontrola m/sTNF + CHX mTNF + CHX
IL-1 (U/ml)
0
20
40
60
80
100
120
140
C
ell
viab
ilti
y (%
)
IL-1/CHX IL-1/CHX/pAb anty-TNF
10 10 10 2 10 3 10 4 1 0
IL-1 (U/ml)
0
20
40
60
80
100
120
140
IL-1/CHX IL-1/CHX/mAb anty-TNF
C
ell
viab
ilit
y (%
)10 10 10 10 10 0 1 2 3 4
IL-1 cytotoxicityIL-1 cytotoxicity
supernatant dilutionsup IL-1/CHX
sup kontr.
sup IL-1
sup CHX
Cel
l via
bilit
y (%
) 4 0 1:4 1:2 1:1 1
0
20
40
60
80
100
120
C
ell v
iabi
lity
(%)
0 1:8 1:4 1:2 1
supernatant dilution
0
20
40
60
80
100
120
sup IL-1/CHX sup IL-1/CHX + pAb anty-TNF
IL-1 cytotoxicityIL-1 cytotoxicity
control
4 h
2 h
0,5 h
1 h
0
100
200
300
400
500
TN
F [
pg
/ml]
control
CHX
IL-1
IL-1/CHX
IL-1 cytotoxicityIL-1 cytotoxicity
Isotype control
Untreated
IL-1/CHX
Survival time of tumor-bearing hamsters
Time [days]
% cumulated survival
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
0 10 20 30 40 50 60 70 80 90 100 110
Ab
Ab-RGD
Ab-LPS
Ab-LPS-RGD
DEPARTMENT OF CELL BIOLOGYDEPARTMENT OF CELL BIOLOGYfinancial supportfinancial 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 BIOLOGYDEPARTMENT OF CELL BIOLOGYselectedselected p previous grantsrevious 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 Tri-City Central Animal LaboratoryCentral Animal Laboratory, , Medical University of GdańskMedical University of Gdańsk
Tri-CityTri-City Central Animal LaboratoryCentral Animal Laboratory, , Medical University of GdańskMedical University of Gdańsk