Volume 49 (2003) No. 5
Avian Endogenous Retroviruses
L. BORISENKO...............................................................177
Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Kiev, Ukraine
Corresponding author: Leonid Borisenko, Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences,
150 Zabolotnogo str., 03143 Kiev, Ukraine. Tel.: 038-044-2663498; fax: 038-04402663498; e-mail:rynditch@imbg.org.ua.
Abstract.
Full text. 177-182
Original Articles
Efficacy and Safety of Inhaled Recombinant Interleukin-2 in High-Risk Renal Cell Cancer Patients Compared
with Systemic Interleukin-2: an Outcome Study
E. Huland1, A. Burger2, J. Fleischer3, P. Fornara4, E. Hatzmann10 A. Heidenreich5, H. Heinzer1, H. Heynemann4, L. Hoffmann6, R. Hofmann5, H. Huland1, I. Kämpfer6, M. Kindler2, H. Kirchner7, G. Mehlhorn8, T. h. Moniak8, U. Rebmann8, J. Roigas9, T. h. Schneider4, D. Schnorr9, H. J. Schmitz3, R. Wenisch3, Z. Varga5, J. Vinke10 .................................................183
1Department of Urology, University Hospital Hamburg-Eppendorf, Germany; 2Onkologische Schwerpunktpraxis, Berlin, Germany;
3St.Carolus Krankenhaus, Görlitz, Germany; 4Martin-Luther-Universität Halle-Wittenberg, Halle, Germany;
5Philipps-Universität Marburg, Marburg, Germany; 6Waldklinikum GmbH, Gera, Germany;
7Klinikum Siloah Germany; 8Diakonissenkrankenhaus, Dessau, Germany; 9Department of Urology, Charite,
Humboldt Universität Berlin, Germany; 10Chiron BV, Amsterdam
Corresponding author: Edith Huland, Department of Urology, and University of Hamburg, Martinistr. 52, 20246 Hamburg, Germany.
Tel: +49 40 42803 4424; Fax: +49 40 42803 4603; e-mail: Huland(zavináč)uke.uni-hamburg.de.
Abstract.
Full text. 183-190
Gamma Irradiation Results in Phosphorylation of p53 at Serine-392 in Human T-Lymphocyte
Leukaemia Cell Line MOLT-4
S. Szkanderová1, J. Vávrová1, M. Řezáčová2, D. Vokurková3, Š. Pavlová4,
J. Šmardová4, J. Stulík
1Institute of Radiobiology and Molecular Pathology, Purkyne Military Medical Academy, Hradec Králové, Czech Republic
Department
2Department of Medical Biochemistry, Faculty of Medicine Hradec Králové, Czech Republic
3Institute of Clinical Immunology and Allergology, University Hospital, Hradec Králové, Czech Republic
4Masaryk Memorial Cancer Institute, Brno, Czech Republic
Corresponding author:Sylva Szkanderová, Institute of Radiobiology and Molecular Pathology, Purkyne Military Medical Academy,
Třebešská 1575, Hradec Králové 500 01, The Czech Republic. Tel: +420 973 25 15 38; Fax: +420 49 551 24 51; e-mail: skanderova@pmfhk.cz.
Abstract.
Full text. 191-196
UVC-Protective Effect of Caffeic Acid on Normal and Transformed Human Skin Cells in Vitro
J. NERADIL1, R. VESELSKÁ1, J. SLANINA2.......................................197
1Cell Culture Laboratory, Department of Biology, Medical Faculty, Masaryk University in Brno, Czech Republic
2Department of Biochemistry, Medical Faculty, Masaryk University in Brno, Czech Republic
Corresponding author: Jakub Neradil, Cell Culture Laboratory, Department of Biology, Medical Faculty,
Masaryk University in Brno, Joštova 10, 662 43 Brno, Czech Republic. Tel.: +420 542 126 386; e-mail: jneradil@med.muni.cz.
Abstract.
Full text. 197-202
Short Communications
Immunotherapy of HPV 16-Associated Tumours with Tumour Cell Line/Dendritic Cell Line (TC-1/DC2.4)
Hybrid Vaccines
J. ŠÍMOVÁ, J. BIEBLOVÁ, T. JANDLOVÁ, J. BUBENÍK.....................203
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Praue, Czech Republic
Corresponding author: Jana Šímová, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic,
Flemingovo nám. 2, 166 37 Praha 6, Czech Republic.
Abstract.
Full text. 203-206
Effects of Adenosine on the Growth of Murine G:5:113 Fibrosarcoma Cells in Vitro
M. HOFER1, Z. HOFEROVÁ1, M. POSPÍŠIL1, V. ZNOJIL2, K. CHRAMOSTOVÁ1........................207
1Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
2Institute of Pathological Physiology, Medical Faculty, Masaryk University, Brno, Czech Republic
Corresponding author: Michal Hofer, Institute of Biophysics, Academy of Sciences of the Czech Republic,
Královopolská 135, CZ-612 65 Brno, Czech Republic.
Abstract.
Full text. 207-210
M. HOFER1, Z. HOFEROVÁ1, M. POSPÍŠIL1, V. ZNOJIL2, K. CHRAMOSTOVÁ1........................207
1Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
2Institute of Pathological Physiology, Medical Faculty, Masaryk University, Brno, Czech Republic
Corresponding author: Michal Hofer, Institute of Biophysics, Academy of Sciences of the Czech Republic,
Královopolská 135, CZ-612 65 Brno, Czech Republic.
Abstract.
Full text. 207-210
Review
Avian Endogenous Retroviruses
L. BORISENKO
Avian Endogenous Retroviruses
L. BORISENKO
Recent data about the diversity of AER, their structure, expression and possible ways of evolution are summarized and analysed
in the present review. Additionally, the role of endogenous retroviruses in ontogenesis and pathology is discussed.
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in the present review. Additionally, the role of endogenous retroviruses in ontogenesis and pathology is discussed.
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Original Articles
Efficacy and Safety of Inhaled Recombinant Interleukin-2 in High-Risk Renal Cell Cancer Patients Compared
with Systemic Interleukin-2: an Outcome Study
E. Huland, A. Burger, J. Fleischer, P. Fornara, E. Hatzmann, A. Heidenreich, H. Heinzer,
H. Heynemann, L. Hoffmann, R. Hofmann, H. Huland, I. Kämpfer, M. Kindler, H. Kirchner,
G. Mehlhorn, T. h. Moniak, U. Rebmann, J. Roigas, T. h. Schneider, D. Schnorr, H. J. Schmitz,
R. Wenisch, Z. Varga, J. Vinke
Efficacy and Safety of Inhaled Recombinant Interleukin-2 in High-Risk Renal Cell Cancer Patients Compared
with Systemic Interleukin-2: an Outcome Study
E. Huland, A. Burger, J. Fleischer, P. Fornara, E. Hatzmann, A. Heidenreich, H. Heinzer,
H. Heynemann, L. Hoffmann, R. Hofmann, H. Huland, I. Kämpfer, M. Kindler, H. Kirchner,
G. Mehlhorn, T. h. Moniak, U. Rebmann, J. Roigas, T. h. Schneider, D. Schnorr, H. J. Schmitz,
R. Wenisch, Z. Varga, J. Vinke
Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases.
Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary
metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were
compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls.
In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily.
The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection
of 3.6‑18.0 MIU rhIL-2. Some patients in both groups also received a-interferon. Mean treatment durations were 43 weeks
rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed
in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years
in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30–0.63; P < 0.0001). The data suggested an association between
the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated.
This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.
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Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary
metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were
compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls.
In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily.
The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection
of 3.6‑18.0 MIU rhIL-2. Some patients in both groups also received a-interferon. Mean treatment durations were 43 weeks
rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed
in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years
in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30–0.63; P < 0.0001). The data suggested an association between
the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated.
This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.
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Gamma Irradiation Results in Phosphorylation of p53 at Serine-392 in Human T-Lymphocyte
Leukaemia Cell Line MOLT-4
S. Szkanderová, J. Vávrová, M. Řezáčová, D. Vokurková, Š. Pavlová,
J. Šmardová, J. Stulík
Exposure of human leukaemia MOLT-4 cells to ionizing irradiation led to apoptosis, which was detected by flow cytometric analysis and degradation of the nuclear lamina. The multiple signalling pathways triggered by either membrane or DNA damage play a critical role in radiation-induced apoptosis. The response to DNA damage is typically associated with the p53 protein accumulation. In this study, we
proved that the transcriptionally active p53 variant occurs in the MOLT-4 cells and its abundance alteration is triggered in the γ-irradiated
cell population concomitantly with phosphorylation at both the serine-392 and serine-15 residues. The p21 upregulation followed the p53 phosphorylation process in irradiated MOLT-4 cells.
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Leukaemia Cell Line MOLT-4
S. Szkanderová, J. Vávrová, M. Řezáčová, D. Vokurková, Š. Pavlová,
J. Šmardová, J. Stulík
Exposure of human leukaemia MOLT-4 cells to ionizing irradiation led to apoptosis, which was detected by flow cytometric analysis and degradation of the nuclear lamina. The multiple signalling pathways triggered by either membrane or DNA damage play a critical role in radiation-induced apoptosis. The response to DNA damage is typically associated with the p53 protein accumulation. In this study, we
proved that the transcriptionally active p53 variant occurs in the MOLT-4 cells and its abundance alteration is triggered in the γ-irradiated
cell population concomitantly with phosphorylation at both the serine-392 and serine-15 residues. The p21 upregulation followed the p53 phosphorylation process in irradiated MOLT-4 cells.
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UVC-Protective Effect of Caffeic Acid on Normal and Transformed Human Skin Cells in Vitro
J. NERADIL, R. VESELSKÁ, J. SLANINA, J. NERADIL, R. VESELSKÁ, J. SLANINA
RecentExposure of human leukaemia MOLT-4 cells to ionizing irradiation led to apoptosis, which was detected by flow cytometric
analysis and degradation of the nucleaPossible UVC-protective properties of CA, a plant phenolic compound with antioxidant activity,
were investigated on human KF1 diploid fibroblast and A431 epidermoid carcinoma cell lines. Cell populations, untreated and treated by antioxidants (CA and α-tocopherol), were irradiated by UVC at the wavelength of 254 nm and their proliferation activity was determined
by the MTT assay. The results show a strong protective effect of CA at both concentrations used (55.5 and 166.5 μM): a significant increase
of proliferation activity after UVC irradiation was detected in both cell populations growing in the presence of CA in comparison with cells in DMEM only. The described protective effect of CA was more obvious in transformed cells than in normal diploid cells. This protective ability
is probably based on the antioxidant and scavenging activities of CA, which seems to be more efficient than α-tocopherol in protection
against the cytotoxic effect caused by UVC irradiation.
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J. NERADIL, R. VESELSKÁ, J. SLANINA, J. NERADIL, R. VESELSKÁ, J. SLANINA
RecentExposure of human leukaemia MOLT-4 cells to ionizing irradiation led to apoptosis, which was detected by flow cytometric
analysis and degradation of the nucleaPossible UVC-protective properties of CA, a plant phenolic compound with antioxidant activity,
were investigated on human KF1 diploid fibroblast and A431 epidermoid carcinoma cell lines. Cell populations, untreated and treated by antioxidants (CA and α-tocopherol), were irradiated by UVC at the wavelength of 254 nm and their proliferation activity was determined
by the MTT assay. The results show a strong protective effect of CA at both concentrations used (55.5 and 166.5 μM): a significant increase
of proliferation activity after UVC irradiation was detected in both cell populations growing in the presence of CA in comparison with cells in DMEM only. The described protective effect of CA was more obvious in transformed cells than in normal diploid cells. This protective ability
is probably based on the antioxidant and scavenging activities of CA, which seems to be more efficient than α-tocopherol in protection
against the cytotoxic effect caused by UVC irradiation.
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Short Communications
Immunotherapy of HPV 16-Associated Tumours with Tumour Cell Line/Dendritic Cell Line (TC-1/DC2.4)
Hybrid Vaccines
J. ŠÍMOVÁ, J. BIEBLOVÁ, T. JANDLOVÁ, J. BUBENÍK
Immunotherapy of HPV 16-Associated Tumours with Tumour Cell Line/Dendritic Cell Line (TC-1/DC2.4)
Hybrid Vaccines
J. ŠÍMOVÁ, J. BIEBLOVÁ, T. JANDLOVÁ, J. BUBENÍK
Hybridization of established dendritic cell lines with tumour cells represents a prospective technology for the construction
of antitumour vaccines. Experiments were designed to examine whether administration of cell populations prepared by fusion of HPV 16-associated tumour TC-1 cells with dendritic cell line DC2.4 could be used for treatment of TC-1 tumours growing in syngeneic mice.
The therapeutic potency of TC-1/DC2.4 fusion vaccine administered 24 h after fusion and that of TC-1/DC2.4 hybrid cells selected
for 3 weeks in HAT?containing medium was tested. It has been found that administration of both types of fusion vaccines at the site
of growing TC-1 tumour transplants significantly inhibited tumour growth with regard to the percentage of tumour-bearing mice
and to the size of the transplanted tumours. Peritumoral administration of the DC2.4 cells alone also reduced the size of growing
TC-1 tumours, but not the percentage of the tumour-bearing mice. Although in the groups of mice treated with fusion vaccines the size of the tumours was reproducibly smaller than that in the mice treated with parental DC2.4 cells, the difference was not statistically significant.
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of antitumour vaccines. Experiments were designed to examine whether administration of cell populations prepared by fusion of HPV 16-associated tumour TC-1 cells with dendritic cell line DC2.4 could be used for treatment of TC-1 tumours growing in syngeneic mice.
The therapeutic potency of TC-1/DC2.4 fusion vaccine administered 24 h after fusion and that of TC-1/DC2.4 hybrid cells selected
for 3 weeks in HAT?containing medium was tested. It has been found that administration of both types of fusion vaccines at the site
of growing TC-1 tumour transplants significantly inhibited tumour growth with regard to the percentage of tumour-bearing mice
and to the size of the transplanted tumours. Peritumoral administration of the DC2.4 cells alone also reduced the size of growing
TC-1 tumours, but not the percentage of the tumour-bearing mice. Although in the groups of mice treated with fusion vaccines the size of the tumours was reproducibly smaller than that in the mice treated with parental DC2.4 cells, the difference was not statistically significant.
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Effects of Adenosine on the Growth of Murine G:5:113 Fibrosarcoma Cells in Vitro
M. HOFER, Z. HOFEROVÁ, M. POSPÍŠIL, V. ZNOJIL, K. CHRAMOSTOVÁ
It has been observed that adenosine suppresses the growth of G:5:113 murine fibrosarcoma cells in vitro with EC50 of 178 mM.
Changes in the cell cycle including decreased percentage of cells in S-phase, increased portion of cells in G0/G1-phase, as well as prolonged generation time were found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, enhanced the growth suppression induced with adenosine in concentrations of 100 and 200 mM. It follows from these results that the action
of adenosine on the G:5:113 cells is extracellular, mediated by adenosine receptors. Elevation of extracellular adenosine might serve
potentially as an anticancer therapeutic agent.
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M. HOFER, Z. HOFEROVÁ, M. POSPÍŠIL, V. ZNOJIL, K. CHRAMOSTOVÁ
It has been observed that adenosine suppresses the growth of G:5:113 murine fibrosarcoma cells in vitro with EC50 of 178 mM.
Changes in the cell cycle including decreased percentage of cells in S-phase, increased portion of cells in G0/G1-phase, as well as prolonged generation time were found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, enhanced the growth suppression induced with adenosine in concentrations of 100 and 200 mM. It follows from these results that the action
of adenosine on the G:5:113 cells is extracellular, mediated by adenosine receptors. Elevation of extracellular adenosine might serve
potentially as an anticancer therapeutic agent.
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