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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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Effects of single radiation treatment on tumour growth.A Modified growth delay to four-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamonds, control; grey diamonds, 5 x 2 Gy; dark grey diamonds, 5 × 3.5 Gy; black diamonds, 5 × 4.5 Gy). B Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control. C Modified growth delay to eight-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamond, control; grey diamond, 5 × 2 Gy; dark grey diamond, 5 × 3.5 Gy; black diamond 5 × 4.5 Gy). D Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control.
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Figure 2: Effects of single radiation treatment on tumour growth.A Modified growth delay to four-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamonds, control; grey diamonds, 5 x 2 Gy; dark grey diamonds, 5 × 3.5 Gy; black diamonds, 5 × 4.5 Gy). B Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control. C Modified growth delay to eight-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamond, control; grey diamond, 5 × 2 Gy; dark grey diamond, 5 × 3.5 Gy; black diamond 5 × 4.5 Gy). D Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control.

Mentions: We first established the appropriate doses of fractionated radiotherapy for the combination experiments (Figure 1A). Fractionated irradiation of the tumours led to a dose-dependent delay in tumour growth. Growth delay to the 4-fold initial tumour volume was 16, 24, 49 and 76 days for untreated controls or 5 fractions of 2 Gy, 3.5 Gy and 4.5 Gy, respectively (Figure 2A/B). The median growth delay to the 8-fold initial tumour volume was 29, 40, 59 and 139 days for the same treatment groups (Figure 2C/D). The growth delay was significant for treatment with 5 × 3.5 Gy and 5 × 4.5 Gy compared to untreated control tumours. In one out of seven animals the tumour was controlled locally upon treatment with 5 × 4.5 Gy after 120 days, whereas all other tumours recurred.


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 single radiation treatment on tumour growth.A Modified growth delay to four-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamonds, control; grey diamonds, 5 x 2 Gy; dark grey diamonds, 5 × 3.5 Gy; black diamonds, 5 × 4.5 Gy). B Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control. C Modified growth delay to eight-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamond, control; grey diamond, 5 × 2 Gy; dark grey diamond, 5 × 3.5 Gy; black diamond 5 × 4.5 Gy). D Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effects of single radiation treatment on tumour growth.A Modified growth delay to four-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamonds, control; grey diamonds, 5 x 2 Gy; dark grey diamonds, 5 × 3.5 Gy; black diamonds, 5 × 4.5 Gy). B Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control. C Modified growth delay to eight-fold of starting volume after fractionated irradiation. Given are Kaplan-Meier-plots of tumours after treatment with increasing doses of fractionated irradiation (open diamond, control; grey diamond, 5 × 2 Gy; dark grey diamond, 5 × 3.5 Gy; black diamond 5 × 4.5 Gy). D Respective computed median growth delay with 95%-confidence interval (n=7-8), * indicates p<0.05 vs. control.
Mentions: We first established the appropriate doses of fractionated radiotherapy for the combination experiments (Figure 1A). Fractionated irradiation of the tumours led to a dose-dependent delay in tumour growth. Growth delay to the 4-fold initial tumour volume was 16, 24, 49 and 76 days for untreated controls or 5 fractions of 2 Gy, 3.5 Gy and 4.5 Gy, respectively (Figure 2A/B). The median growth delay to the 8-fold initial tumour volume was 29, 40, 59 and 139 days for the same treatment groups (Figure 2C/D). The growth delay was significant for treatment with 5 × 3.5 Gy and 5 × 4.5 Gy compared to untreated control tumours. In one out of seven animals the tumour was controlled locally upon treatment with 5 × 4.5 Gy after 120 days, whereas all other tumours recurred.

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