1993 Fiscal Year Final Research Report Summary
New drug delivery system for cancer chemotherapy using lipid commpositions characteristic of cancer cell membrane
| Project/Area Number |
04807145
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima Univ., Scho. of Dent., Assistant Prof., 歯学部・附属病院, 講師 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
TAKADA Kazuaki Hiroshima Univ., Scho. of Dent. Prof., 歯学部, 教授 (30029970)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Squamous carcinoma / Adenocarcinoma / Anti cancer drug / Lipid composition / Photodynamic therapy / Liposome / drug delivery system / Serum-free culture |
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| Research Abstract |
It has been known that the effects of anti cancer drug is dependent of histological typing of the target cancer cells. We have speculated that the heterogeneity of the frug effect is resulted from the defference of membrane hydrophobicity of the target cancer cells. One of major factors determine membrace hydrophobicity membrane lipid compositions.
On the first research year, we have studied lipid metabolism and lipid compositions of several oral squamous cell carcinoma cells(SCC) and salibary gland derived adenocarcinoma cells(SAC) in serum-free cell culture. We have found that 80% of total SCC membrane lipid is phosphokipid and 20% is free cholesterol. On the other hand, 80% of total SAC membrane lipid is meutral lipid such as trigriceride and eaterified cholesterol, and 20% is phospholipid, these results apparently revealed that the lipid composition of SCC membrane is defferent from that of SAC and suggest that hydrophobicith of SCC membrane is higher than that of SAC membrane.
On the second research year, we have studied the effects of bleomycin (BLM), peplomycin(PLM), cis-platinum(CDDP) and carboplatin(CDBCA) on the growth of weveral SCC and SAC in werum-free cell culture, the cytotoxic activities of BLM and PLM on SCC are stronger than these on SAC.On the other hand, the activities of CDDp and CDBCA on SAC are stronger than these on SCC.Furthermore, these activities are dependent on the intra-cellular concentration of the drugs. These results strongly suggest that cytotoxic effect of anticancer drug are dependent on the hydrophobicity of the cancer cell membrane. We are currently planning to study the effect of lipisome that is complexed anticancer drug with membrane lipid which is the same as lipid composition of target cell membrane.
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