| Project/Area Number |
03454385
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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 |
Urology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOSHIDA Osamu Kyoto Univesity, Faculty of Medicine, Professor, 医学部, 教授 (70025584)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Youichi Kyoto University, Faculty of Medicine, Instructor, 医学部, 助手 (10243031)
TERACHI Toshiro Kyoto University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50207487)
HASHIMURA Takayuki Kyoto University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (40189478)
OISHI Kenji Kyoto University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10152042)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Urological tumor / Cytotoxic Lymphocyte / BCG / CK-432 / CDDP / PSK / TNF / BSO |
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| Research Abstract |
We demonstrate the following results :
1. Protein-bound polysaccharide Kreha ( PSK ) augments cytotoxic activity of peripheral blood lymphocytes ( PBL ) against urinary bladder tumor cells in vitro and in vivo in patients with urinary bladder tumor. The PSK-mediated enhancement of cytotoxicity of PBL may be largely due to an alpha-1, 4-glucan of less than 50 kd.
2. Bacillus Calmette-Guerin ( BCG ) activates the tumor killing system through stimulation of effector cells and elevation of target cell susceptibility to lysis by cytotoxic lymphocytes in patients with urinary bladder tumor. Furthermore, BCG-augmented cytotoxicity may be specifically oriented to urinary bladder tumor cells.
3. Combination treatment of MBT-2 murine urinary bladder tumor cell line transplanted into C3H/He mice with BCG and exogenous fibrinogen prolongs accumulation of BCG by trapping BCG in fibrin meshwork, and induces marked infiltration of inflammatory cells into tumor stroma, causing marked regression of the tu
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mor.
4. Like BCG, OK-432 activates the autologous tumor killing system through stimulation of effector cells and enhancement of target cell susceptibility to lysis by effector cells in patients with urinary bladder tumor. Moreover, the OK-432-augmented target sensitivity to lysis by cytotoxic lymphocytes may be oriented specifically to urinary bladder tumor cells.
5. Cis-diamminedichloroplatinum ( II ) ( CDDP ) has an augmenting effect on the susceptibility of urinary bladder tumor cells to the cell-mediated cytotoxicity partly through a modification of cell membrane and inhibition of DNA synthesis.
6. Cytotoxic lymphocytes activated by tumor cells produce various kinds of cytokines such as tumor necrosis factor-alpha ( TNF-alpha ) which exert cytotoxic activity against tumor cells. TNF-alpha in combination with CDDP, buthionine sulfoximine ( BSO ) or pentoxifylline ( PTX ) overcomes the TNF-alpha-resistance of renal cell carcinoma cells. Downregulation of TNF-alpha mRNA by CDDP, BSO or PTX may play a role in the enhanced cytotoxicity seen with TNF-alpha in combination with CDDP, BSO or PTX. Less
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