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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) on apoptosis detected by TUNEL assay. The images were taken at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of in situ apoptosis assay at different times (24 hours, 3 days, and 7 days) after the indicated treatments (E).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Apoptotic cells are indicated by the arrows.Abbreviation: TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
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f4-ott-7-1801: Effect of sonodynamic therapy (SDT) on apoptosis detected by TUNEL assay. The images were taken at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of in situ apoptosis assay at different times (24 hours, 3 days, and 7 days) after the indicated treatments (E).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Apoptotic cells are indicated by the arrows.Abbreviation: TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Mentions: At 24 hours after treatment with SDT, in situ apoptosis assay showed a marked increase in the cell apoptosis rate. The apoptotic rate of glioma cells with SDT was much higher than that with the other treatments (Figure 4), which strongly suggests that SDT can induce apoptosis. TUNEL results showed that there were few apoptotic cells in the HMME treatment group and in the control rats. Further, there was no statistical difference in apoptotic rate between each time point in these two groups. At 24 hours after treatment, the apoptotic rate in rats treated with US alone was higher than that of rats that received HMME treatment alone and control rats. However, there was no statistical difference in apoptotic rate between the mentioned groups at 3 or 7 days after treatment.


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) on apoptosis detected by TUNEL assay. The images were taken at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of in situ apoptosis assay at different times (24 hours, 3 days, and 7 days) after the indicated treatments (E).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Apoptotic cells are indicated by the arrows.Abbreviation: TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4199795&req=5

f4-ott-7-1801: Effect of sonodynamic therapy (SDT) on apoptosis detected by TUNEL assay. The images were taken at 24 hours after treatment with SDT (A), ultrasound (US) (B), and hematoporphyrin monomethyl ether (HMME) (C), or after no treatment (D). Summary of in situ apoptosis assay at different times (24 hours, 3 days, and 7 days) after the indicated treatments (E).Notes: Data are presented as the mean ± standard deviation (n=8); *P<0.01 versus control. Apoptotic cells are indicated by the arrows.Abbreviation: TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
Mentions: At 24 hours after treatment with SDT, in situ apoptosis assay showed a marked increase in the cell apoptosis rate. The apoptotic rate of glioma cells with SDT was much higher than that with the other treatments (Figure 4), which strongly suggests that SDT can induce apoptosis. TUNEL results showed that there were few apoptotic cells in the HMME treatment group and in the control rats. Further, there was no statistical difference in apoptotic rate between each time point in these two groups. At 24 hours after treatment, the apoptotic rate in rats treated with US alone was higher than that of rats that received HMME treatment alone and control rats. However, there was no statistical difference in apoptotic rate between the mentioned groups at 3 or 7 days after treatment.

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