1995 Fiscal Year Final Research Report Summary
Experimental study of prevention of liver metastases from gastrointestinal cancer by locoregional chemotherapy
| Project/Area Number |
05671096
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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 | St.Marianna University |
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Principal Investigator |
YAMAMURA Takuya St.Marianna University, Faculty of Medicine, assistant professor, 医学部, 助教授 (90114701)
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| Co-Investigator(Kenkyū-buntansha) |
SEO Keisuke St.Marianna University, Faculty of Medicine, instructor, 医学部, 助手 (00247363)
AKAISHI Osamu St.Marianna University, Faculty of Medicine, instructor, 医学部, 助手 (30231799)
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| Project Period (FY) |
1993 – 1995
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| Keywords | gastrointestinal cancer / liver metastasis / continuous intraportal chemotherapy / 5-fluorouracil / cancer suppressor gene |
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| Research Abstract |
Efficacy of prevention of liver metastases by continuous intraportal chemotherapy (CIPC) was studied pharmacokinetically and clinically. Relationship between cancer suppressor gene and liver metastases was also studied. Results were as follows : 1) Experimental studies regarding prevention of liver metastases by CIPC of Adriamycin ; regarding difference of commencement of treatment, inhibition of liver metastases was more effective in the group in which treatment starts immediately after inoculationo f tumor cells. Complete inhibition of liver metastases was obtained in case small number oftumor cells was inoculated. Relationship between concentration of Adriamycin and efficacy of inhibition was positive. These results showed that effective prevention of liver metastases was obtained by CIPC in case number of tumor cells was small in portal vein and high concentration of drug was administered in early stage of metastasis formation. 2) Pharmacokinetics of CIPC of 5-fluorouracil (5FU) ;
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concentratino of 5FU in portal vein, concentration of FdUMP and TS inhibition rate in liver were kept high with continuous intraportal infusion of 5FU.TS inhibition rate, concentration of 5FU and FdUMP in liver was increased in proportion to administration dose of 5FU.However, TS inhibition rate showed low level in the extreme high dose administration of 5FU.3) Clinical results of CIPC of 5FU for prevention of liver metastases after resection of colorectal cancer ; Recurrence rate was decreaed 70% by CIPC of 5FU compared with control group. 4) Relationship between overexpression of cancer suppressor gene in colorectal cancer and liver metastases showed positive.
These results showed that CIPC of 5FU was effective for prevention of liver metastases after resection of colorectal cancer clinically and pharmacokinetically. Clinical studies regarding optimal administration dose of 5FU or combination of other drugs with 5FU,relationship between expression of suppressor gene and efficacy of chemotherapy are necessary. Less
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