Abstract
Despite various therapeutic interventions, glioblastoma multiforme (GBM) is one of the most highly vascularized neoplasms in humans with poor prognosis. In this study, we show that a single i.m. injection of an adeno-associated viral (AAV) vector expressing angiostatin, a potent angiogenic inhibitor, effectively suppresses human glioma growth in the brain of nude mice. Approximately 40% of the tumor-bearing mice treated with AAV-angiostatin vector survived for >10 months (the duration of the experiments). In contrast, 100% of the tumor-bearing mice in the control groups, with or without i.m. injection of a control vector AAV-GFP, died because of excessive tumor burden by 6 weeks. High levels of angiostatin produced by the AAV vector were detected in blood circulation for >250 days after the one-time vector injection. The secreted angiostatin specifically targeted neovessels in the brain tumors, as evidenced by the diminished vessel densities and increased apoptosis of tumor cells surrounding these neovessels. Our study thus demonstrates that AAV-mediated antiangiogenesis gene therapy offers efficient and sustained systemic delivery of the therapeutic product, which in turn effectively suppresses glioma growth in the brain.
| Original language | English |
|---|---|
| Pages (from-to) | 756-763 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 62 |
| Issue number | 3 |
| Publication status | Published - Feb 1 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. / Ma, Hsin I.; Guo, Ping; Li, Juan; Lin, Shinn Zong; Chiang, Yung Hsiao; Xiao, Xiao; Cheng, Shi Yuan.
In: Cancer Research, Vol. 62, No. 3, 01.02.2002, p. 756-763.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin
AU - Ma, Hsin I.
AU - Guo, Ping
AU - Li, Juan
AU - Lin, Shinn Zong
AU - Chiang, Yung Hsiao
AU - Xiao, Xiao
AU - Cheng, Shi Yuan
PY - 2002/2/1
Y1 - 2002/2/1
N2 - Despite various therapeutic interventions, glioblastoma multiforme (GBM) is one of the most highly vascularized neoplasms in humans with poor prognosis. In this study, we show that a single i.m. injection of an adeno-associated viral (AAV) vector expressing angiostatin, a potent angiogenic inhibitor, effectively suppresses human glioma growth in the brain of nude mice. Approximately 40% of the tumor-bearing mice treated with AAV-angiostatin vector survived for >10 months (the duration of the experiments). In contrast, 100% of the tumor-bearing mice in the control groups, with or without i.m. injection of a control vector AAV-GFP, died because of excessive tumor burden by 6 weeks. High levels of angiostatin produced by the AAV vector were detected in blood circulation for >250 days after the one-time vector injection. The secreted angiostatin specifically targeted neovessels in the brain tumors, as evidenced by the diminished vessel densities and increased apoptosis of tumor cells surrounding these neovessels. Our study thus demonstrates that AAV-mediated antiangiogenesis gene therapy offers efficient and sustained systemic delivery of the therapeutic product, which in turn effectively suppresses glioma growth in the brain.
AB - Despite various therapeutic interventions, glioblastoma multiforme (GBM) is one of the most highly vascularized neoplasms in humans with poor prognosis. In this study, we show that a single i.m. injection of an adeno-associated viral (AAV) vector expressing angiostatin, a potent angiogenic inhibitor, effectively suppresses human glioma growth in the brain of nude mice. Approximately 40% of the tumor-bearing mice treated with AAV-angiostatin vector survived for >10 months (the duration of the experiments). In contrast, 100% of the tumor-bearing mice in the control groups, with or without i.m. injection of a control vector AAV-GFP, died because of excessive tumor burden by 6 weeks. High levels of angiostatin produced by the AAV vector were detected in blood circulation for >250 days after the one-time vector injection. The secreted angiostatin specifically targeted neovessels in the brain tumors, as evidenced by the diminished vessel densities and increased apoptosis of tumor cells surrounding these neovessels. Our study thus demonstrates that AAV-mediated antiangiogenesis gene therapy offers efficient and sustained systemic delivery of the therapeutic product, which in turn effectively suppresses glioma growth in the brain.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036468564&partnerID=8YFLogxK
M3 - Article
C2 - 11830530
AN - SCOPUS:0036468564
VL - 62
SP - 756
EP - 763
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 3
ER -