Page 372 - 2014 Printable Abstract Book
P. 372
underlying the protective effects of MSC therapy may allow to design new therapeutic strategies to
abrogate the tumor-promoting effects of irradiated stroma.
(PS7-34) Parthenolide as a radioprotector of non-tumoral tissue in the treatment of prostate cancer.
2
1
1
3
1
Katherine L. Morel ; Rebecca J. Ormsby ; Eva Bezak ; Wayne D. Tilley ; and Pamela J. Sykes , Molecular
Medicine and Pathology, Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre,
2
1
Adelaide, Australia ; Department of Medical Physics, Royal Adelaide Hospital, Adelaide, Australia ; and
Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research Centre, School
of Medicine, University of Adelaide and Hanson Institute, Adelaide, Australia
3
Current radiotherapy protocols for prostate cancer can be associated with undesirable side
effects, such as impotence and incontinence due to damage to normal tissues. Improvements or new
approaches for treatment are required. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumour
properties and also selectively exhibits a radiosensitisation effect on prostate cancer cell lines, while
inducing radioresistance in primary prostate epithelial cell lines in vitro. These properties of PTL could be
utilised to improve radiotherapy by killing more tumour cells and less normal cells. Low doses of radiation
prior to high dose irradiation have demonstrated protection from cell death and DNA damage. We aimed
to study the effect of PTL treatment and low dose radiation on radiosensitivity in normal animals and in a
prostate tumour model, the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). Tumour
development is confined to prostate tissues in the TRAMP model, allowing observation of both tumour
and healthy tissues within the same animal. In pilot studies investigating the effect of PTL in normal tissues
in mice, male C57BL/6 mice were treated with either 40 mg/kg PTL or 10% Ethanol/Saline vehicle thrice
weekly for one week prior to 6 Gy whole-body X-irradiation. Six hours post-irradiation the apoptosis
frequency was analysed. PTL caused significant protection of normal tissue from high dose radiation
induced apoptosis in normal dorsolateral prostate (34.5% reduction, p = 0.002) and spleen (17.3%
reduction, p = 0.041) of C57BL/6 mice compared to mice treated with vehicle control. Similar
radioprotection from apoptosis was observed in TRAMP spleen. When a low dose (10 mGy) of whole body
X-irradiation was delivered 3 hours prior to the high dose (6 Gy), apoptosis in C57BL/6 prostate was again
reduced in the presence of PTL with a trend towards increased radioprotection in tissues receiving a
priming low X-ray dose. These results suggest that PTL may be a useful radioprotector of normal tissues
during radiotherapy and that the addition of 10 mGy prior to a high X-radiation exposure may enhance
this effect. Ongoing studies are aimed at determining if PTL and low dose radiation protect from cell death
in rectum and bladder tissues, with PLT also exhibiting tumour-specific radiosensitisation of prostate
tumour tissue.
(PS7-35) The thioredoxin mimetic R-910 inhibits radiation-induced lung apoptosis when delivered either
1
1
1
1
prophylactically or therapeutically. Julie A. Wilder ; Katherine M. Gott ; Yuanyuan Shi ; Glenda D'Egidio ;
2
1
2
2
1
Garry J. Southan ; Prakash Jagtap ; Jacob M. McDonald ; Andrew Salzman ; and Ivan O. Rosas
2
1
Lovelace Respiratory Research Institute, Albuquerque, NM and Radikal Therapeutics, Inc., Beverly, MA
Rationale: Previous studies have shown that radiation-induced pulmonary fibrosis is preceded by
lung cell apoptosis in a murine model of the disease. Apoptosis develops within one week of whole thorax
radiation exposure, whereas fibrosis development is not readily evident until week 16 post-radiation. In
370 | P a g e
abrogate the tumor-promoting effects of irradiated stroma.
(PS7-34) Parthenolide as a radioprotector of non-tumoral tissue in the treatment of prostate cancer.
2
1
1
3
1
Katherine L. Morel ; Rebecca J. Ormsby ; Eva Bezak ; Wayne D. Tilley ; and Pamela J. Sykes , Molecular
Medicine and Pathology, Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre,
2
1
Adelaide, Australia ; Department of Medical Physics, Royal Adelaide Hospital, Adelaide, Australia ; and
Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research Centre, School
of Medicine, University of Adelaide and Hanson Institute, Adelaide, Australia
3
Current radiotherapy protocols for prostate cancer can be associated with undesirable side
effects, such as impotence and incontinence due to damage to normal tissues. Improvements or new
approaches for treatment are required. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumour
properties and also selectively exhibits a radiosensitisation effect on prostate cancer cell lines, while
inducing radioresistance in primary prostate epithelial cell lines in vitro. These properties of PTL could be
utilised to improve radiotherapy by killing more tumour cells and less normal cells. Low doses of radiation
prior to high dose irradiation have demonstrated protection from cell death and DNA damage. We aimed
to study the effect of PTL treatment and low dose radiation on radiosensitivity in normal animals and in a
prostate tumour model, the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). Tumour
development is confined to prostate tissues in the TRAMP model, allowing observation of both tumour
and healthy tissues within the same animal. In pilot studies investigating the effect of PTL in normal tissues
in mice, male C57BL/6 mice were treated with either 40 mg/kg PTL or 10% Ethanol/Saline vehicle thrice
weekly for one week prior to 6 Gy whole-body X-irradiation. Six hours post-irradiation the apoptosis
frequency was analysed. PTL caused significant protection of normal tissue from high dose radiation
induced apoptosis in normal dorsolateral prostate (34.5% reduction, p = 0.002) and spleen (17.3%
reduction, p = 0.041) of C57BL/6 mice compared to mice treated with vehicle control. Similar
radioprotection from apoptosis was observed in TRAMP spleen. When a low dose (10 mGy) of whole body
X-irradiation was delivered 3 hours prior to the high dose (6 Gy), apoptosis in C57BL/6 prostate was again
reduced in the presence of PTL with a trend towards increased radioprotection in tissues receiving a
priming low X-ray dose. These results suggest that PTL may be a useful radioprotector of normal tissues
during radiotherapy and that the addition of 10 mGy prior to a high X-radiation exposure may enhance
this effect. Ongoing studies are aimed at determining if PTL and low dose radiation protect from cell death
in rectum and bladder tissues, with PLT also exhibiting tumour-specific radiosensitisation of prostate
tumour tissue.
(PS7-35) The thioredoxin mimetic R-910 inhibits radiation-induced lung apoptosis when delivered either
1
1
1
1
prophylactically or therapeutically. Julie A. Wilder ; Katherine M. Gott ; Yuanyuan Shi ; Glenda D'Egidio ;
2
1
2
2
1
Garry J. Southan ; Prakash Jagtap ; Jacob M. McDonald ; Andrew Salzman ; and Ivan O. Rosas
2
1
Lovelace Respiratory Research Institute, Albuquerque, NM and Radikal Therapeutics, Inc., Beverly, MA
Rationale: Previous studies have shown that radiation-induced pulmonary fibrosis is preceded by
lung cell apoptosis in a murine model of the disease. Apoptosis develops within one week of whole thorax
radiation exposure, whereas fibrosis development is not readily evident until week 16 post-radiation. In
370 | P a g e
