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5-Aminolevulinic acid-induced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo
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5-Aminolevulinic acid-induced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo
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5-Aminolevulinic acid-induced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo
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Journal Article
5-Aminolevulinic acid-induced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo
2015
Overview
Ionizing irradiation is a well-established therapeutic modality for malignant gliomas. Due to its high cellular uptake, 5-aminolevulinic acid (ALA) is used for fluorescence-guided resection of malignant gliomas. We have previously shown that 5-ALA sensitizes glioma cells to irradiation in vitro. The aim of the present study was to assess whether 5-ALA acts as a radiosensitizer in experimental glioma in vivo. Rats were subcutaneously injected with 9L gliosarcoma cells and administered 5-ALA. The accumulation of 5-ALA-induced protoporphyrin IX was confirmed by high-performance liquid chromatography (HPLC) analysis. Subcutaneous (s.c.) tumors were subsequently irradiated with 2 Gy/day for five consecutive days. In the experimental glioma model, high-performance liquid chromatography analysis revealed a high level of accumulation of 5-ALA-induced protoporphyrin IX in s.c. tumors 3 h after 5-ALA administration. Multi-dose ionizing irradiation induced greater inhibition of tumor growth in rats that were administered 5-ALA than in the non-5-ALA-treated animals. Immunohistochemical analysis of the s.c. tumors revealed that numerous ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages gathered at the surface of and within the s.c. tumors following multi-dose ionizing irradiation in combination with 5-ALA administration. By contrast, the s.c. tumors in the control group scarcely showed aggregation of Iba1-positive macrophages. These results suggested that multi-dose ionizing irradiation with 5-ALA induced not only a direct cytotoxic effect but also enhanced the host antitumor immune response and thus caused high inhibition of tumor growth in experimental glioma.
Publisher
D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
Subject
/ Aminolevulinic Acid - pharmacology
/ Animals
/ Calcium
/ Cancer
/ Chromatography, High Pressure Liquid
/ Cytotoxicity, Immunologic - drug effects
/ Cytotoxicity, Immunologic - radiation effects
/ Glioma
/ Gliomas
/ High-performance liquid chromatography
/ ionized calcium-binding adapter molecule 1
/ Male
/ Necrosis
/ Protoporphyrins - biosynthesis
/ Radiation-Sensitizing Agents - pharmacology
/ Rats
/ Rodents
/ Skin
/ Solvents
/ Tumor Burden - radiation effects
/ Tumors
