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Early life-stage effects in medaka (Oryzias latipes) following in ovo exposure to polyamine biosynthetic inhibitors.

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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.

Sequential inhibition of polyamine synthesis. A phase I trial of DFMO (alpha-difluoromethylornithine) and methyl-GAG [methylglyoxal-bis(guanylhydrazone)].

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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

Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A (CGP48664) in patients with metastatic melanoma.

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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

A Phase I Dose-Escalation Study of the Polyamine Analog PG-11047 in Patients With Advanced Solid Tumors

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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

Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer.

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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

A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours.

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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

A phase I and pharmacokinetic study of SAM486A, a novel polyamine biosynthesis inhibitor, administered on a daily-times-five every-three-week schedule in patients with Advanced solid malignancies.

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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

Phase I trial of alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer.

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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 preliminary study of microcapsule suspension for hemolysis evaluation of artificial organs.

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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 in rat brain during exercise. Effect of arginine and some phosphorylated amino acids.

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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,

Phase I study of combined alpha interferon, alpha difluoromethylornithine (DFMO), and doxorubicin in advanced malignancy.

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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

Phase 1 study of N(1),N(11)‑diethylnorspermine (DENSPM) in patients with advanced hepatocellular carcinoma.

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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

Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients with recurrent glioma.

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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

Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice.

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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

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