Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with alpha-difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or
Bleomycin
(
Bleo
). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in
ornithine decarboxylase
(
ODC
), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in
ODC
and polyamine values in these cells were similar to those produced in the more sensitive parental line.
...
PMID:Schedule dependent potentiation of antitumor drug effects by alpha-difluoromethylornithine in human gastric carcinoma cells in vitro. 169 47
Polyamines are essential for normal and neoplastic growth.
Ornithine decarboxylase
(
ODC
) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of
ODC
, and a known anti-neoplastic agent. The purpose of this study was to examine the susceptibility of various human cancers to inhibition by DFMO in vivo. We have studied three human pancreatic adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas (LS-180 and WIDR), and three metastatic cell lines of a human gastric adenocarcinoma (BHM, BMM,
BLM
) that were growing in congenitally athymic (nude) Balb/c mice. Mice bearing each tumor were divided into two groups; one group served as controls and the other group received DFMO 3% in drinking water. Tumor growth and weight, and content of DNA, RNA, protein and polyamines were determined and correlated. DFMO significantly inhibited the growth of three of the three gastric tumors, two of the three pancreatic tumors and neither of the two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern that was parallel to tumor growth. The tumor polyamine concentration did not correlate with sensitivity to DFMO. These findings provide clear evidence for important differences in the sensitivity of various human cancers to growth inhibition by DFMO and indicate that endogenous polyamine levels alone do not predict the sensitivity of the tumors to DFMO.
...
PMID:Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo. 198 77
