Linked Life Data

8653704

Source:http://linkedlifedata.com/resource/pubmed/id/8653704

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1996-7-30
pubmed:abstractText
The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2602-6
pubmed:dateRevised
2006-4-24
pubmed:meshHeading
pubmed-meshheading:8653704-Adenocarcinoma, pubmed-meshheading:8653704-Animals, pubmed-meshheading:8653704-Antineoplastic Agents, pubmed-meshheading:8653704-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:8653704-Cell Division, pubmed-meshheading:8653704-Colonic Neoplasms, pubmed-meshheading:8653704-Drug Combinations, pubmed-meshheading:8653704-Fluorouracil, pubmed-meshheading:8653704-Humans, pubmed-meshheading:8653704-Neoplasm Metastasis, pubmed-meshheading:8653704-Neoplasm Transplantation, pubmed-meshheading:8653704-Oxonic Acid, pubmed-meshheading:8653704-Prodrugs, pubmed-meshheading:8653704-Pyridines, pubmed-meshheading:8653704-RNA, pubmed-meshheading:8653704-Rats, pubmed-meshheading:8653704-Rats, Nude, pubmed-meshheading:8653704-Tegafur, pubmed-meshheading:8653704-Transplantation, Heterologous
pubmed:year
1996
pubmed:articleTitle
Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.
pubmed:affiliation
Institute for Pathogenic Biochemistry in Medicine, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.
pubmed:publicationType
Journal Article