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Study of the mechanism of sonodynamic therapy in a rat glioma model.

Song D, Yue W, Li Z, Li J, Zhao J, Zhang N - Onco Targets Ther (2014)

Bottom Line: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo.In contrast, the effect of SDT could last at least 2 weeks.Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.

ABSTRACT

Purpose: The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains.

Methods: Two weeks after inoculation, glioma development was evaluated by measuring tumor volume using a 1.5 T magnetic resonance imager. Rats that had a well-developed C6 glioma (usually when the tumor diameter reached 3-5 mm) were used to test SDT, ultrasound-alone, and HMME-alone treatments. Rats both administered and not administered intravenous HMME 10 μg/mL were insonated by a 1 MHz ultrasound at a dose of 0.5 W/cm(2).

Results: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo. The treatment with ultrasound alone could inhibit glioma growth within 1 week; however, 1 week later, the tumor started growing again. In contrast, the effect of SDT could last at least 2 weeks. Injection of HMME alone had no effects on inhibiting glioma growth, suggesting the sonosensitizer HMME has no antitumor effect. Both SDT and ultrasound-alone treatment could extend the survival of rats implanted with a C6 glioma. Pathological and electron microscopic examinations suggested SDT and ultrasound-alone treatment could induce glioma necrosis by way of triggering glioma-cell apoptosis, which was confirmed by immunohistological examination with cytochrome-c and caspase-3 antibodies. Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.

Conclusion: This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.

No MeSH data available.


Related in: MedlinePlus

Effect of sonodynamic therapy (SDT) treatment on glioma angiogenesis. Immunohistochemical staining with CD34 antibody at 24 hours (A), 3 days (B), and 7 days (C) after treatment with SDT. Summary of the effect of SDT, US and HMME on microvessel density (MVD) evaluated by counting CD34-positive microvessels (D). Immunohistochemical staining with vascular endothelial growth factor (VEGF) antibody at 24 hours (E), 3 days (F), and 7 days (G) after treatment with SDT. Summary of the effect of SDT, US and HMME on VEGF levels (H).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control.Abbreviations: US, ultrasound; HMME, hematoporphyrin monomethyl ether.
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f6-ott-7-1801: Effect of sonodynamic therapy (SDT) treatment on glioma angiogenesis. Immunohistochemical staining with CD34 antibody at 24 hours (A), 3 days (B), and 7 days (C) after treatment with SDT. Summary of the effect of SDT, US and HMME on microvessel density (MVD) evaluated by counting CD34-positive microvessels (D). Immunohistochemical staining with vascular endothelial growth factor (VEGF) antibody at 24 hours (E), 3 days (F), and 7 days (G) after treatment with SDT. Summary of the effect of SDT, US and HMME on VEGF levels (H).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control.Abbreviations: US, ultrasound; HMME, hematoporphyrin monomethyl ether.

Mentions: The MVD and VEGF protein expression level were similar in rats treated with HMME alone and control rats at each of the examined time points (Figure 6). At 24 hours after treatment, MVD and VEGF protein expression showed a decreased trend in the US treatment alone group compared with in control rats and those treated with HMME alone; however, there was no statistical difference between these groups at 3 and 7 days after treatment. At 24 hours after SDT, the MVD and VEGF protein expression was much lower than at the same time point with any other treatment. The lamellar necrosis or sporadic punctiform necrosis cells were found in slices. By 3 days after treatment, the protein expression level of VEGF with SDT increased a little, but was still lower than with other treatments. At the same time, the size of the area of lamellar necrosis was observed to be clearly smaller than that at 24 hours after treatment, and the number of necrosis cells also decreased substantially. At 7 days after treatment, no statistical difference in the expression level of VEGF or MVD was found between each treatment group.


Study of the mechanism of sonodynamic therapy in a rat glioma model.

Song D, Yue W, Li Z, Li J, Zhao J, Zhang N - Onco Targets Ther (2014)

Effect of sonodynamic therapy (SDT) treatment on glioma angiogenesis. Immunohistochemical staining with CD34 antibody at 24 hours (A), 3 days (B), and 7 days (C) after treatment with SDT. Summary of the effect of SDT, US and HMME on microvessel density (MVD) evaluated by counting CD34-positive microvessels (D). Immunohistochemical staining with vascular endothelial growth factor (VEGF) antibody at 24 hours (E), 3 days (F), and 7 days (G) after treatment with SDT. Summary of the effect of SDT, US and HMME on VEGF levels (H).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control.Abbreviations: US, ultrasound; HMME, hematoporphyrin monomethyl ether.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199795&req=5

f6-ott-7-1801: Effect of sonodynamic therapy (SDT) treatment on glioma angiogenesis. Immunohistochemical staining with CD34 antibody at 24 hours (A), 3 days (B), and 7 days (C) after treatment with SDT. Summary of the effect of SDT, US and HMME on microvessel density (MVD) evaluated by counting CD34-positive microvessels (D). Immunohistochemical staining with vascular endothelial growth factor (VEGF) antibody at 24 hours (E), 3 days (F), and 7 days (G) after treatment with SDT. Summary of the effect of SDT, US and HMME on VEGF levels (H).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control.Abbreviations: US, ultrasound; HMME, hematoporphyrin monomethyl ether.
Mentions: The MVD and VEGF protein expression level were similar in rats treated with HMME alone and control rats at each of the examined time points (Figure 6). At 24 hours after treatment, MVD and VEGF protein expression showed a decreased trend in the US treatment alone group compared with in control rats and those treated with HMME alone; however, there was no statistical difference between these groups at 3 and 7 days after treatment. At 24 hours after SDT, the MVD and VEGF protein expression was much lower than at the same time point with any other treatment. The lamellar necrosis or sporadic punctiform necrosis cells were found in slices. By 3 days after treatment, the protein expression level of VEGF with SDT increased a little, but was still lower than with other treatments. At the same time, the size of the area of lamellar necrosis was observed to be clearly smaller than that at 24 hours after treatment, and the number of necrosis cells also decreased substantially. At 7 days after treatment, no statistical difference in the expression level of VEGF or MVD was found between each treatment group.

Bottom Line: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo.In contrast, the effect of SDT could last at least 2 weeks.Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.

ABSTRACT

Purpose: The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains.

Methods: Two weeks after inoculation, glioma development was evaluated by measuring tumor volume using a 1.5 T magnetic resonance imager. Rats that had a well-developed C6 glioma (usually when the tumor diameter reached 3-5 mm) were used to test SDT, ultrasound-alone, and HMME-alone treatments. Rats both administered and not administered intravenous HMME 10 μg/mL were insonated by a 1 MHz ultrasound at a dose of 0.5 W/cm(2).

Results: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo. The treatment with ultrasound alone could inhibit glioma growth within 1 week; however, 1 week later, the tumor started growing again. In contrast, the effect of SDT could last at least 2 weeks. Injection of HMME alone had no effects on inhibiting glioma growth, suggesting the sonosensitizer HMME has no antitumor effect. Both SDT and ultrasound-alone treatment could extend the survival of rats implanted with a C6 glioma. Pathological and electron microscopic examinations suggested SDT and ultrasound-alone treatment could induce glioma necrosis by way of triggering glioma-cell apoptosis, which was confirmed by immunohistological examination with cytochrome-c and caspase-3 antibodies. Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.

Conclusion: This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.

No MeSH data available.


Related in: MedlinePlus