Nakano Yoshiteru
   Department   School of Medicine  Neurosurgery, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title 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.
Journal Formal name:Molecular medicine reports
Abbreviation:Mol Med Rep
ISSN code:17913004/17912997
Volume, Issue, Page 11(3),1813-9頁
Author and coauthor Yamamoto Junkoh, Ogura Shun-Ichiro, Shimajiri Shohei, Nakano Yoshiteru, Akiba Daisuke, Kitagawa Takehiro, Ueta Kunihiro, Tanaka Tohru, Nishizawa Shigeru
Publication date 2015/03
Summary 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.
DOI 10.3892/mmr.2014.2991
PMID 25420581