14 結果
Medaka, Oryzias latipes, were exposed in ovo to the polyamine (PA) biosynthesis inhibitors alpha-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG). In an additional group, spermine, the end product of the PA pathway, was added with DFMO and MGBG for a "rescue" treatment.
Both DFMO and methyl-GAG inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells, we initiated a phase-I study of these agents in patients with advanced cancer. DFMO was given by mouth at a constant
OBJECTIVE
To determine the activity and tolerability of SAM496A, an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma who had not received prior chemotherapy. Selected patients were offered participation in two sub-studies examining early changes in tumor
Purpose: Polyamines are essential for the sustained proliferation and biomass required by tumor cells. Bis-alkylated polyamine analogs are nonfunctional competitors of natural polyamines. Of these, PG-11047, a second-generation unsaturated analog of the polyamine
OBJECTIVE
The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.
METHODS
Patients with advanced
Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme
OBJECTIVE
SAM486A is a novel inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC). This study was performed to characterize the toxicity profile and the pharmacological behavior and to determine the maximum tolerated dose (MTD) of SAM486A administered by a 1-h
Both alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells and DFMO combined with MGBG has shown synergistic
A microcapsule suspension, a substitute for animal blood in hemolysis tests, has been developed for evaluation of the absolute hemolytic properties of circulatory artificial organs. The microcapsule suspension was made by dispersing microcapsule slurry into an ethylene glycol sodium chloride
RNA and protein synthesis is noticeably depressed in the brain of swimming rats. Repeated oral administration of phosphothreonine, phosphoserine or arginine is susceptible of improving brain macromolecular synthesis. A parallel induction is observed on spermine and spermidine accumulation,
Interferon (IFN) and conventional cytotoxic chemotherapeutic agents have been successfully combined in various studies. Alpha difluoromethylornithine (DFMO) is a novel antitumor agent which is an inhibitor of polyamine metabolism. A phase I study of IFN 24 x 10(6) U/m2/day IM (days 3-7), DFMO 9
OBJECTIVE
N(1),N(11)-diethylnorspermine (DENSPM), a synthetic analog of the naturally occurring polyamine spermine, can induce polyamine depletion and inhibit tumor cell growth. The objectives of this phase I study were to assess the safety, maximum-tolerated dose (MTD), pharmacokinetics, and
Interferons alpha and beta have been reported to cause tumor regression in a small proportion of patients with recurrent glioma. Eflornithine, an irreversible inhibitor of ornithine decarboxylase, reduces cellular polyamine levels and has also been reported to cause tumor regression in patients with
To identify mechanisms of anabolic androgen action in muscle, we generated male and female genomic androgen receptor (AR) knockout (ARKO) mice, and characterized muscle mass, contractile function, and gene expression. Muscle mass is decreased in ARKO males, but normal in ARKO females. The levator