1992 Fiscal Year Final Research Report Summary
Inhibitors of cytotoxic T cell activities produced by cultured tumor cells.
| Project/Area Number |
03454466
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 |
TAKADA Kazuaki Hiroshima Univ. Sch of Dent., Professor, 歯学部, 教授 (30029970)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Tetsuzi Hiroshima Univ. Dental Hospital, Assistant Professor, 歯学部・附属病院, 講師 (00169153)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Patients with malignant tumor / Cellular-immune response / Interleukin-2 / Lymphokine-activated killer cells / Serum-free medium / Insulin / Transforming growth factor-beta / Heparin-binding factors |
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| Research Abstract |
It has been reported that patients with malignant tumors have a defective cellularimmune status. We have speculated that this defect was resulted from the production of soluble immuno-suppressive factors produced by tumor cells.
We have established serum-free culture system to induce highly cytotoxic lymphokine activated killer (LAK)cells. Using this system, we have studied several growth factors, hormons and medium conditioned by several tumor cells on the growth and cytotoxic activities of LAK cells. Following results were obtained.
1. The LAK cells induced in RD medium supplemented with interleukin-2, human transferrin, 2-mercaptoethanol, 2-aminoethanol and sodium selenite had 3 to 4 times higher cytotoxic activities against tumor cells than the LAK cells in human serum supplemented medium.
2. Insulin or insulin like growth factor-I(IGF-I) which has been produced by many tumor cells as an autocrine or a paracrine growth factor inhibited cytotoxic activities of LAK cells.
3. Transforming growth factor-beta (TGF-beta) inhibited both of the growth and cytotoxic activities of LAK cells.
4. The medium conditioned by cultured squamous carcinoma cells (SCC) and malignant melanoma cells(MM) derived from oral region inhibited both of the growth and cytotoxic activities of LAK cells.
5. Physical and chemical analysis revealed that the suppressive activities of SCC were heat- and acid-resistant but those of MM were heat- and acid-labile. These results suggest that the activities of SCC were different from those of MM.
6. We have fractionated SCC derived activities by heparin-sepharose affinity chromatography. It has been revealed that the fractions which were eluted with 0.9-1.2M NaCl exhibited significant activities which were different from TGF-beta and insulin.
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