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Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice.

Henke G, Meier V, Lindner LH, Eibl H, Bamberg M, Belka C, Budach W, Jendrossek V - Radiat Oncol (2012)

Bottom Line: Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice.Further studies are needed to evaluate efficacy of extended drug treatment schedules.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiooncology, University Hospital Tübingen, Hoppe-Seyler-Str, 3, Tübingen 72076, Germany.

ABSTRACT

Background: Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods: In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.

Results: We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions: We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

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Related in: MedlinePlus

Effects of combination treatment on relative tumour volume. Animals received no irradiation combined with 8 injections of vehicle (open black circles, n=18) or 40 mg/kg BW Erufosine (red circles, n=21). Alternatively, animals received fractionated irradiation (5 × 3.3 Gy) combined with 8 injections of vehicle (open white squares, n=14) or 40 mg/kg BW Erufosine (red squares, n=20). Erufosine was given daily before the onset of radiotherapy and every 48h during the course of fractionated irradiation. Grey bar notifies treatment time. * indicates p<0.05 vs. control, # indicates p<0.05 vs. irradiation alone. Median relative tumour volume is given with upper and lower 95% confidence intervals.
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Figure 3: Effects of combination treatment on relative tumour volume. Animals received no irradiation combined with 8 injections of vehicle (open black circles, n=18) or 40 mg/kg BW Erufosine (red circles, n=21). Alternatively, animals received fractionated irradiation (5 × 3.3 Gy) combined with 8 injections of vehicle (open white squares, n=14) or 40 mg/kg BW Erufosine (red squares, n=20). Erufosine was given daily before the onset of radiotherapy and every 48h during the course of fractionated irradiation. Grey bar notifies treatment time. * indicates p<0.05 vs. control, # indicates p<0.05 vs. irradiation alone. Median relative tumour volume is given with upper and lower 95% confidence intervals.

Mentions: The course of the median tumour volume in the four treatment groups is depicted in Figure 3. As expected, fractionated irradiation with 5 × 3.3 Gy led to a transient decrease in median tumour volume and a delay in tumour growth which became significant after 14 days. However, the transient early growth delay observed during short-term treatment with Erufosine alone was not maintained upon discontinuation of drug treatment in the longer follow-up and no decrease in tumour volume was detected upon Erufosine treatment without irradiation. Nevertheless, the addition of Erufosine qualitatively enhanced the decrease in tumour volume induced by radiotherapy alone, yielding significant differences when the irradiation groups were compared (Figure 3).


Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice.

Henke G, Meier V, Lindner LH, Eibl H, Bamberg M, Belka C, Budach W, Jendrossek V - Radiat Oncol (2012)

Effects of combination treatment on relative tumour volume. Animals received no irradiation combined with 8 injections of vehicle (open black circles, n=18) or 40 mg/kg BW Erufosine (red circles, n=21). Alternatively, animals received fractionated irradiation (5 × 3.3 Gy) combined with 8 injections of vehicle (open white squares, n=14) or 40 mg/kg BW Erufosine (red squares, n=20). Erufosine was given daily before the onset of radiotherapy and every 48h during the course of fractionated irradiation. Grey bar notifies treatment time. * indicates p<0.05 vs. control, # indicates p<0.05 vs. irradiation alone. Median relative tumour volume is given with upper and lower 95% confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539870&req=5

Figure 3: Effects of combination treatment on relative tumour volume. Animals received no irradiation combined with 8 injections of vehicle (open black circles, n=18) or 40 mg/kg BW Erufosine (red circles, n=21). Alternatively, animals received fractionated irradiation (5 × 3.3 Gy) combined with 8 injections of vehicle (open white squares, n=14) or 40 mg/kg BW Erufosine (red squares, n=20). Erufosine was given daily before the onset of radiotherapy and every 48h during the course of fractionated irradiation. Grey bar notifies treatment time. * indicates p<0.05 vs. control, # indicates p<0.05 vs. irradiation alone. Median relative tumour volume is given with upper and lower 95% confidence intervals.
Mentions: The course of the median tumour volume in the four treatment groups is depicted in Figure 3. As expected, fractionated irradiation with 5 × 3.3 Gy led to a transient decrease in median tumour volume and a delay in tumour growth which became significant after 14 days. However, the transient early growth delay observed during short-term treatment with Erufosine alone was not maintained upon discontinuation of drug treatment in the longer follow-up and no decrease in tumour volume was detected upon Erufosine treatment without irradiation. Nevertheless, the addition of Erufosine qualitatively enhanced the decrease in tumour volume induced by radiotherapy alone, yielding significant differences when the irradiation groups were compared (Figure 3).

Bottom Line: Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice.Further studies are needed to evaluate efficacy of extended drug treatment schedules.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiooncology, University Hospital Tübingen, Hoppe-Seyler-Str, 3, Tübingen 72076, Germany.

ABSTRACT

Background: Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods: In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.

Results: We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions: We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

Show MeSH
Related in: MedlinePlus