Treatment of tumour cell with 5-aza-2-deoxycytidine (DAC) for immune tumour therapy of Glioma in Fischer-344 rats
Author
Summary, in English
Fisher 344 rats with implanted N29 glioma tumours were treated with Pulsed
Electric Fields (PEF) in combination with immunization using either IFN-gamma-gene-transfected syngeneic tumour cells or IFN-gamma transfected N29 cells
treated with 10 micro-M 5-aza-2-deoxycytidine (DAC).
Tumours (N29) were inoculated subcutaneously on both thighs of female F-
344 syngeneic rats. The left tumour was treated once with 16 exponential
pulses with an electric field strength of 1400 V/cm, and 1.0 ms duration (time constant). No anticancer drugs were given at any time. The following day and then once weekly for three weeks, the animals were given intra-peritoneal
injections of irradiated, modified N29 tumour cells.
The results were evaluated by daily measuring the size of tumour on both
sides of the animals. Treatment with solely PEF in 32 animals resulted in a
specific growth rate decrease of 20±6 % on the PEF exposed tumour. The
effect at the non targeted tumour was negligible (0±4 %). Treatment with
IFN-gamma secreting tumour cells resulted in a significant decrease of tumour
growth rate on the right tumour of 20± 2 % (p< 0.05) and no significant
effect (3±0.3% ) was observed on the left tumour. Immunization with DAC
treated IFN-gamma secreting cells in 12 animals showed no significant decreased
growth rate, on neither the left nor the right tumours.
By combining PEF+IFN-gamma no significant decrease in growth rate was achieved.
But in the combination of PEF and IFN-gamma secreting cells grown in DAC medium
the tumour growth rate decreased by about 50 % at the PEF treated tumour
and there was a decrease of about 20% in tumour growth at the non-PEF
treated tumour rate which is about the same as for PEF treatment alone.
Immune therapy of rats with intracranial N32 tumours by immunization with
IFN-gamma secreting syngeneic cells treated with DAC resulted in a slight (3%) but
not significant increase in survival time. With a single RT fraction of 15 Gy
there was, however, a significant increase of 32% in the length of survival
time of the rats with N32 tumours (p<0.02). Radiation therapy with a single
fraction of 15 Gy combined with immunization with IFN-gamma secreting syngeneic
cells treated with DAC resulted in significant (p<0.01) 34% increased length
of survival time for the N32 tumours although there were no complete
remissions.
Electric Fields (PEF) in combination with immunization using either IFN-gamma-gene-transfected syngeneic tumour cells or IFN-gamma transfected N29 cells
treated with 10 micro-M 5-aza-2-deoxycytidine (DAC).
Tumours (N29) were inoculated subcutaneously on both thighs of female F-
344 syngeneic rats. The left tumour was treated once with 16 exponential
pulses with an electric field strength of 1400 V/cm, and 1.0 ms duration (time constant). No anticancer drugs were given at any time. The following day and then once weekly for three weeks, the animals were given intra-peritoneal
injections of irradiated, modified N29 tumour cells.
The results were evaluated by daily measuring the size of tumour on both
sides of the animals. Treatment with solely PEF in 32 animals resulted in a
specific growth rate decrease of 20±6 % on the PEF exposed tumour. The
effect at the non targeted tumour was negligible (0±4 %). Treatment with
IFN-gamma secreting tumour cells resulted in a significant decrease of tumour
growth rate on the right tumour of 20± 2 % (p< 0.05) and no significant
effect (3±0.3% ) was observed on the left tumour. Immunization with DAC
treated IFN-gamma secreting cells in 12 animals showed no significant decreased
growth rate, on neither the left nor the right tumours.
By combining PEF+IFN-gamma no significant decrease in growth rate was achieved.
But in the combination of PEF and IFN-gamma secreting cells grown in DAC medium
the tumour growth rate decreased by about 50 % at the PEF treated tumour
and there was a decrease of about 20% in tumour growth at the non-PEF
treated tumour rate which is about the same as for PEF treatment alone.
Immune therapy of rats with intracranial N32 tumours by immunization with
IFN-gamma secreting syngeneic cells treated with DAC resulted in a slight (3%) but
not significant increase in survival time. With a single RT fraction of 15 Gy
there was, however, a significant increase of 32% in the length of survival
time of the rats with N32 tumours (p<0.02). Radiation therapy with a single
fraction of 15 Gy combined with immunization with IFN-gamma secreting syngeneic
cells treated with DAC resulted in significant (p<0.01) 34% increased length
of survival time for the N32 tumours although there were no complete
remissions.
Publishing year
2012
Language
English
Pages
1-21
Publication/Series
Acta Scientiarum Lundensia
Volume
2012
Issue
007
Document type
Journal article
Publisher
Bertil RR Persson, Medical Radiation Physics, 22185 Lund, Sweden
Topic
- Radiology, Nuclear Medicine and Medical Imaging
Keywords
- RT
- radiation therapy
- glioma
- Fischer rat
- Abscopal
- non-target
- Tumor growth rate
- TGR
- Immunization
- syngeneic tumor cells
- interferon-gamma
- IFNg.
Status
Published
ISBN/ISSN/Other
- ISSN: 1651-5013