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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 the expression of protein cytochrome-c (Cyto-C) and protein caspase-3. Immunohistochemical staining with Cyto-C antibody at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of the effect of SDT on protein Cyto-C (E). Immunohistochemical staining with caspase-3 antibody at 24 hours after treatment with SDT (G), US (H), and HMME (I), or no treatment (J). Summary of the effect of SDT on protein caspase-3 (F).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Positively stained cells are indicated by arrow.
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f5-ott-7-1801: Effect of sonodynamic therapy (SDT) treatment on the expression of protein cytochrome-c (Cyto-C) and protein caspase-3. Immunohistochemical staining with Cyto-C antibody at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of the effect of SDT on protein Cyto-C (E). Immunohistochemical staining with caspase-3 antibody at 24 hours after treatment with SDT (G), US (H), and HMME (I), or no treatment (J). Summary of the effect of SDT on protein caspase-3 (F).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Positively stained cells are indicated by arrow.

Mentions: Twenty-four hours after treatment (Figure 5), the expression rate of both Cyto-C protein and caspase-3 protein was much higher in rats treated with SDT than in those treated with any of the other treatments. However, at this time point, the protein expression rate in rats treated with US alone was also higher than that of rats treated with HMME alone and control rats. Few cells expressed Cyto-C and Caspase-3 in the HMME-alone and control groups at different time points, and no difference in the expression rate of Cyto-C and caspase-3 protein was found between the two groups. At 3 and 7 days after treatment, the protein expression rate was obviously decreased with all treatments. No statistical difference in protein expression rate was found between each of the treatments. This suggests that both SDT and US alone can trigger apoptosis, although SDT can prolong this initiating effect much longer. HMME treatment alone had no effect on initiating apoptosis.


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 the expression of protein cytochrome-c (Cyto-C) and protein caspase-3. Immunohistochemical staining with Cyto-C antibody at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of the effect of SDT on protein Cyto-C (E). Immunohistochemical staining with caspase-3 antibody at 24 hours after treatment with SDT (G), US (H), and HMME (I), or no treatment (J). Summary of the effect of SDT on protein caspase-3 (F).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Positively stained cells are indicated by arrow.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ott-7-1801: Effect of sonodynamic therapy (SDT) treatment on the expression of protein cytochrome-c (Cyto-C) and protein caspase-3. Immunohistochemical staining with Cyto-C antibody at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of the effect of SDT on protein Cyto-C (E). Immunohistochemical staining with caspase-3 antibody at 24 hours after treatment with SDT (G), US (H), and HMME (I), or no treatment (J). Summary of the effect of SDT on protein caspase-3 (F).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Positively stained cells are indicated by arrow.
Mentions: Twenty-four hours after treatment (Figure 5), the expression rate of both Cyto-C protein and caspase-3 protein was much higher in rats treated with SDT than in those treated with any of the other treatments. However, at this time point, the protein expression rate in rats treated with US alone was also higher than that of rats treated with HMME alone and control rats. Few cells expressed Cyto-C and Caspase-3 in the HMME-alone and control groups at different time points, and no difference in the expression rate of Cyto-C and caspase-3 protein was found between the two groups. At 3 and 7 days after treatment, the protein expression rate was obviously decreased with all treatments. No statistical difference in protein expression rate was found between each of the treatments. This suggests that both SDT and US alone can trigger apoptosis, although SDT can prolong this initiating effect much longer. HMME treatment alone had no effect on initiating apoptosis.

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