| Project/Area Number |
63570648
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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 |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
YOSHINO Keiichi Keio University School of Medicine, Department of Surgery, assistant professor, 医学部, 専任講師 (10101982)
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| Co-Investigator(Kenkyū-buntansha) |
FUKASE Tatsu Keio University School of Medicine, resident, 医学部, 助手 (90199159)
SUZUKI Fumio Keio University School of Medicine, resident, 医学部, 助手 (50179248)
KATAI Hitoshi Keio University School of medicine, resident, 医学部, 助手 (20169460)
OTANI Yoshihide Keio University School of medicine, resident, 医学部, 助手 (20168983)
KUBOUCHI Kiyoshi Keio University School of Medicine, resident, 医学部, 助手 (10146607)
SHIMADA Atsushi Keio University School of Medicine, resident (30216056)
MATSUI Hideo Keio University School of medicine, resident (50209483)
AIZAWA Kenichiro Keio University School of medicine, resident (20202442)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Cancer / Degree of Biological Malignancy / Collagen / Prolylhydroxylase / Interstitial Collagenase / Type IV Collagen Degrading Enzyme / 3-Hydroxyproline / TIMP / 癌の進展 / 蛋白分解酵素 / IV型コラゲナ-ゼ / 癌の転移 / 胃癌 / I型コラゲナーゼ / IV型コラゲナーゼ / 基底膜 / IV型コラーゲン / 尿中3ーhydroxyproline |
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| Research Abstract |
Activities of tissue prolylhydroxylase, a key enzyme in collagen synthesis, interstitial collagenase (Iase) and type IV collagen (main component of basement membrane) degrading enzyme (IV ase) were revealed to be more intense in the tissue of the central region and advancing front of gastric cancer than in adjacent and distal noncancerous gastric epithelium. Enzyme activities were determined by 3H release assay, fibril assay and solution assay, respectively.
The activity of IV ase in the advancing front was revealed to be more intense in cases of marked lymph node metastases.
Amino acid analyzer was used to study 3-hydroxyproline in urine, which is regarded as a metabolite of type IV collagen, the main component of basement membrane. The value was corrected for renal function, i. e. divided by the value of creatinine in urine. 3-hydroxyproline was revealed to be increased in patients with advanced gastric cancer compared with patients with early gastric cancer and healthy persons.
Cocultu
… More
re studies of various established human gastric cancer cell lines and established human fibroblast cell lines were performed. Under phase contrast microscopy, the fibroblasts showed atrophic changes in the coculture with well differentiated adenocarcinoma cells. Zymographies of supernatant obtained from the culture soup using SDS-polyacryl-amide gel-added gelatin revealed that Iase activity was more intense in the coculture of well differentiated adenocarcinoma cells and that the activity of TIMP was lower in the coculture of signet ring cell.
These results suggest that Iase and IV ase contribute to advancement of cancer, expansive development and lymph node metastasis, respectively, there is close relationship between cancerous advancement and basement membrane, TIMP plays some role at formation of scirrhous cancer of signet ring cell and following clinical applications are seemed to be possible : the activity of prolylhydroxylase shows degree of cancer stage, the activity of IV ase shows degree of biological malignancy of cancer, determination of 3-hydroxypoline in urine is applied for cancer screening of mass population. Less
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