Limits...
Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

Sharpe MA, Livingston AD, Gist TL, Ghosh P, Han J, Baskin DS - EBioMedicine (2015)

Bottom Line: Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone.MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB.We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Kenneth R. Peak Brain and Pituitary Tumor Center, Houston Methodist Hospital, 6565 Fannin, Suite 944, Houston, TX 77030, United States.

ABSTRACT
The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

No MeSH data available.


Related in: MedlinePlus

MP-MUS is a chemotherapeutic in a flank glioblastoma model.(A) Three treatments of 8 mg/kg of MP-MUS were able to halt tumor growth compared with saline controls.(B) A single treatment of 8 mg/kg MP-MUS was able to shrink tumor volume by 50% in 24 h.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4588367&req=5

f0025: MP-MUS is a chemotherapeutic in a flank glioblastoma model.(A) Three treatments of 8 mg/kg of MP-MUS were able to halt tumor growth compared with saline controls.(B) A single treatment of 8 mg/kg MP-MUS was able to shrink tumor volume by 50% in 24 h.

Mentions: We examined the effects of two MP-MUS treatment regimens on primary human glioma xenografts in a Nu/Nu nude mouse model (Fig. 5). Saline or 0.2 mg MP-MUS in saline was injected into the tail veins of mice (≈ 25 g), 8 mg/kg, on days 0, 12, and 23 with seven mice per group (Fig. 5A). None of the mice exhibited adverse symptoms or weight loss during the study period. Tumor volumes shrank in the MP-MUS treatment group after the first injection, whereas tumors in the saline controls grew steadily throughout the study. Tumor volumes were significantly different between groups (p < 0.0005) from day 22 onward.


Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

Sharpe MA, Livingston AD, Gist TL, Ghosh P, Han J, Baskin DS - EBioMedicine (2015)

MP-MUS is a chemotherapeutic in a flank glioblastoma model.(A) Three treatments of 8 mg/kg of MP-MUS were able to halt tumor growth compared with saline controls.(B) A single treatment of 8 mg/kg MP-MUS was able to shrink tumor volume by 50% in 24 h.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588367&req=5

f0025: MP-MUS is a chemotherapeutic in a flank glioblastoma model.(A) Three treatments of 8 mg/kg of MP-MUS were able to halt tumor growth compared with saline controls.(B) A single treatment of 8 mg/kg MP-MUS was able to shrink tumor volume by 50% in 24 h.
Mentions: We examined the effects of two MP-MUS treatment regimens on primary human glioma xenografts in a Nu/Nu nude mouse model (Fig. 5). Saline or 0.2 mg MP-MUS in saline was injected into the tail veins of mice (≈ 25 g), 8 mg/kg, on days 0, 12, and 23 with seven mice per group (Fig. 5A). None of the mice exhibited adverse symptoms or weight loss during the study period. Tumor volumes shrank in the MP-MUS treatment group after the first injection, whereas tumors in the saline controls grew steadily throughout the study. Tumor volumes were significantly different between groups (p < 0.0005) from day 22 onward.

Bottom Line: Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone.MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB.We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Kenneth R. Peak Brain and Pituitary Tumor Center, Houston Methodist Hospital, 6565 Fannin, Suite 944, Houston, TX 77030, United States.

ABSTRACT
The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

No MeSH data available.


Related in: MedlinePlus