Document Detail

Mechanism of photofrin-enhanced ultrasound-induced human glioma cell death.
MedLine Citation:
PMID:  19414325     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Low-intensity ultrasound showed tumor cell killing by a non-thermal effect in human leukemia cells. The aim of our study was to investigate the efficacy of low-intensity ultrasound on malignant astrocytic tumor cells with the photosensitizer, Photofrin, which is taken up by the cell surface receptor, low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR). MATERIALS AND METHODS: Cells were sonicated with continuous wave ultrasound with or without the presence of Photofrin (75 mg/ml) at an intensity of 0.3 W/cm(2) for a duration of 5, 15, or 30 s. RESULTS: Ultrasound alone induced instant cell killing immediately after sonication in both U251MG and U105MG malignant gliomas cells. In U251MG cells, which expressed LRP/alpha2MR, significant enhancement of cell killing was observed following Photofrin pretreatment, 52.7+/-17.5%, 13.0+/-4.6% and 3.9+/-0.9% for 5, 15, and 30 s respectively (p<0.05). This enhancement of cell killing was abolished by preincubation with receptor-associated protein (RAP) which binds specifically to LRP/alpha2MR. This enhancement by Photofrin was not achieved in U105MG which did not express LRP/alpha2MR. U251MG cells accumulated 2.43+/-0.25 Photofrin mg/mg protein, which significantly decreased with RAP pretreatment (1.38+/-0.22 Photofrin mg/mg protein) (p<0.05). U105MG cells accumulated 1.31+/-0.16 Photofrin mg/mg protein, which was significantly less than in U251MG cells. Photofrin uptake was not altered by RAP pretreatment in U105MG cells. U251MG cells exposed to ultrasound in the presence of Photofrin showed multiple surface pores and dimple-like craters. CONCLUSION: This is the first report to demonstrate the usefulness of low-intensity ultrasound for the cell killing of malignant glioma cells. Antitumor activity might be enhanced by combination with photosensitizer, which is transported by cell surface LRP/alpha2-MR to some degree.
Shuji Hayashi; Masaki Yamamoto; Katsuhiro Tachibana; Yushi Ueno; Guojun Bu; Takeo Fukushima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-06-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  897-905     Citation Subset:  IM    
Department of Neurosurgery, Fukuoka University School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan.
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MeSH Terms
Brain Neoplasms / pathology,  therapy*
Cell Survival / drug effects*
Combined Modality Therapy
Dihematoporphyrin Ether / therapeutic use*
Glioma / pathology,  therapy*
LDL-Receptor Related Protein 1 / genetics,  metabolism
Photosensitizing Agents / therapeutic use*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Ultrasonic Therapy*
alpha-Macroglobulins / genetics,  metabolism
Reg. No./Substance:
0/LDL-Receptor Related Protein 1; 0/Photosensitizing Agents; 0/RNA, Messenger; 0/alpha-Macroglobulins; 97067-70-4/Dihematoporphyrin Ether

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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