Development of photodynamic therapy to early stage oral cancer using drug delivery system
| Project/Area Number |
11470438
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TORATANI Shigeaki Hospital of Dental School, HIROSHIMA UNIVERSITY, Assistant Professor, 歯学部・附属病院, 講師 (90172220)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Tetsuji Faculty of Dentistry, HIROSHIMA UNIVERSITY, Professor, 歯学部, 教授 (00169153)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | photodynamic therapy / liposome / hematoporphyrin derivative / active oxigen / lipid composition of membrane / squamous cell carcinoma / adenocarcinoma from salivary gland / 光照射 / 扁平上皮癌 |
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| Research Abstract |
Photodynamic therapy (PDT) using both hematoporphyrin derivative (HPD) and photoradiation has had a high rate of effectiveness in combatting early stage cancers. We have studied, to apply this therapy to treatment of oral cancer, on verious type of cultured carcinoma cells derived from oral cancers.
It has been revealed that squamous cell carcinoma cells (SCC) exhibited high sensitivity to PDT in comparison with salivary gland-derived adenocarcinoma cells (SAC). It became clear that SAC exhibited an increased level of reduced glutathion and glutathion peroxidase activity in comparison to those of SCC.The SCC which showed decreased sensitivity to PDT, exhibited a extremerly high level of glutathion S-transferase activity. Consequenly, the function of glutathion cascade were factors determining photosensitivity of the cells. In addition, the SCC demonstrated an increased intracellular level of drug compare to that SAC.So we have investigated lipid composition of cell-membrane of both cells under serum-free culture. It became evident that 60% of membrane lipids of SCC was phospholipids (PL) and 80% of those of SAC was neutral lipids (NL). The NL/PL ratio indicated that SCC showed low levels but SAC showed remarkably high levels. These result indicated that the cytotoxity of PDT correlated with the intracellular levels of drug resulted from the difference of membrane hydrophobicity.
Thus, we have designed liposome which is comparable to the lipid composition of SCC cell membrane, constructed the liposome-entrapped anti-cancer drugs and examined sensitivity to this liposome of both SCC and SAC by growth assay. As the result, the liposome-entrapped drug exhibited enhanced cytotoxicity on SCC compare to either drug alone or drug-liposome mixture.
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Report
(3 results)
Research Products
(4 results)
