| Project/Area Number |
63480357
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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 | Akita University |
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Principal Investigator |
KATO Tetsuro Akita University Urology Assistant Professor, 医学部, 助教授 (40004642)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Masahiro Akita University, Pathology, Assistant, 医学部, 助手 (70162229)
WATANUKI Tsutomu Akita University, Pathology, Professor, 医学部, 教授 (30004550)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1989: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | urinary bladder cancer / transitional cell carcinoma / c-erbB-2 / multidrug resistant gene / immunohistological analysis / oncogene / epidermal growth factor / epidermal growth factor receptor / 免疫組織化学 / 予後因子 / 遺伝子増幅 / 尿路上皮癌 / P-glycoprotein / multidrug-resistance / MDR-1 / urinary bladder cancer / kidney cancer / c-erbB-2 / EGF-receptor / cancer family syndrome / 組織異型 / DNA合成細胞 / 遺伝子 / 分化 |
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| Research Abstract |
1. The c-erbB-2 gene product was demonstrated immunoelectron microscopically in human transitional cell carcinomas of the urinary tract. The immune reaction with the monoclonal antibody was confined to cell membranes with a linear pattern. Amorphous deposits in the intercellular spaces were also immunoreactive with the monoclonal antibody directed to an extracellular epitope, suggesting that a part of the c-erbB-2 gene product may be released from the cancer cell membranes into the extracellular space.
2. Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in human bladder cancer immunohistologically and by Western blot analysis. The c-erbB-2 gene product was more frequently expressed in high grade tumors and in high stage tumors. while the expression of EGF-R was independent of these two parameters. These results suggest that c-erbB-2 may play a different role from EGF-R to control some specific reaction of cancer cell, also it may
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be used as a tumor maker for the malignant potential.
3. Expression of cerbB-2 gene product could be detected immunohistologically in paraffin-embeddedtissue specimen of transitional cell carcinoma. Positive rate of this staining was 26%. Five year survival rate of patients with cerbB-2 positive cancer was significantly shorter than that of patients with cerbB-2 negative cancer (p<0.05). Dot blot hybridization analysis using genomic DNA extracted from the cerbB-2 positive specimen demonstrated that the gene was not amplified in all patients with cerbB-2 positive cancer.
These results suggest that cerbB-2 expression may be applicable as a tumor marker of malignant potential and prognostic factor of human transitional carcinoma.
4. Localization of product of the human mdr1 standing for multidrug resistant gene was investigated with monoclonal antibody MRK-16 in normal kidney. Renal cell cancer and urinary bladder cancer. The mdr1 gene product was localized on cell membrane and there was no correlation between its expression rate and histological grading.
5. Oncogene amplication in siblings of cancer family syndrome. In which 4 of 7 sidlings developed 1 to 3 primary carcinomas from the gastrointestinal and/or genitourinary organs before 50-year old. Was surveyed using DNA prepared from paraffin- embedded block. Of 8 tumors from 3 siblings H-ras was amplified in 1, c-myc in 6 and c-erbB-2 in 1. The oncogene amplification in this cancer family would be a consequence of hereditary predisposition and may have promote the early manifestation of these tumors. Less
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