Disease relevance of acivicin

• These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL [1].
• Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin [1].
• We conclude that cotreatment with Aminosyn or a mixture of large neutral amino acids could protect cancer patients from acivicin-induced CNS toxicity without ablating antitumor efficacy [2].
• Effects of acivicin and dipyridamole on hepatoma 3924A cells [3].
• We have developed a variant of P388 leukemia resistant to acivicin (P388/ACIA) and compared its properties with those of the parent line (P388/S) [4].

Psychiatry related information on acivicin

• In humans acivicin causes reversible, dose-limiting central nervous system (CNS) effects including somnolence, ataxia, personality changes, and hallucinations [2].

High impact information on acivicin

• The pig enzyme, which has Ala-523 in place of Thr-523, is inhibited by acivicin with esterification at Ser-405 [5].
• Basal CD14 and CD11b expression were slightly reduced by DEX and PTX, but neither drug modified the acivicin-induced increases [6].
• Thus, DEX and PTX effectively block the acivicin-induced expression of TNF-alpha and IL-1 beta, but they have little influence on the acivicin-induced differentiation process.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• DEX and PTX did not alter cell growth, and did not block the acivicin-induced block in growth [6].
• DEX and PTX reduced the acivicin-induced increases in TNF-alpha and IL-1 beta mRNA expression, but they had little or no effect on the acivicin-induced decreases in expression of mRNA for c-myc and c-myb [6].

Chemical compound and disease context of acivicin

• Enhancement of the sensitivity of human colon cancer cells to growth inhibition by acivicin achieved through inhibition of nucleic acid precursor salvage by dipyridamole [7].
• Inhibition of gamma-glutamyl transpeptidase activity by acivicin in vivo protects the kidney from cisplatin-induced toxicity [8].
• Collateral sensitivity to N-(phosphonacetyl)-L-aspartic acid in a line of P388 leukemia cells selected for resistance to L-(alpha S, 5S)-alpha-amino-3- chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) [9].
• Pretreatment of rats with acivicin prevents hydroquinone-mediated nephrotoxicity, indicating that toxicity is dependent on the formation of metabolites that require processing by gamma-GT [10].
• Phase II trials of 5-day vinblastine infusion (NSC 49842), L-alanosine (NSC 153353), acivicin (NSC 163501), and aminothiadiazole (NSC 4728) in patients with recurrent or metastatic renal cell carcinoma [11].

Biological context of acivicin

• In ECV304 cells and human umbilical venous endothelial cells, acivicin favored Hcy plus Cu2+-induced apoptosis whereas dexamethasone counteracted the apoptotic process [12].
• Acivicin pharmacokinetics were studied in Phase I patients receiving i.v. treatment on single-dose or daily x5 (daily times five doses) regimens repeated every 3 weeks [13].
• Acivicin kinetics appeared to be dose-independent over the range of 8.5-150 mg/m2/day [13].
• Based on previous reports of the biochemical mechanisms of Acivicin actions, several additives to the tissue culture medium were tested for their ability to protect MiaPaCa-2 cells from inhibition of cell cycle progression [14].
• This study was designed to determine the effects of acivicin on the levels of HL-60 cell mRNA transcripts of several cytokines, growth factors, and protooncogenes implicated in the control of hematopoietic cell proliferation and differentiation [15].

Anatomical context of acivicin

• The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL) [1].
• Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells [1].
• Acivicin given to one patient at 8.5 mg/m2/day on the daily x5 schedule caused a 70% reduction in leukocyte CPS II activity within 5 h after therapy was initiated [13].
• Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture [2].
• Rapid efflux of Acivicin occurred with both cell lines at 37 degrees, but efflux from 3T3 cells was greatly diminished at 0 degrees [16].

Associations of acivicin with other chemical compounds

• Enhancement of antitumor activity of glutamine antagonists 6-diazo-5-oxo-L-norleucine and acivicin in cell culture by glutaminase-asparaginase [16].
• Phase I clinical trial of a combination of dipyridamole and acivicin based upon inhibition of nucleoside salvage [17].
• The primary metabolic effect of acivicin was depletion of the cytidine triphosphate and guanosine triphosphate pools [7].
• Control HL-60 cells did not express mRNA for granulocyte-colony-stimulating factor, granulocyte-macrophage-colony-stimulating factor, interleukin 3, or interleukin 6, and acivicin or phorbol myristate acetate did not induce their expression [15].
• Blood urea nitrogen and serum creatinine levels confirmed the protective effect of acivicin [8].

Gene context of acivicin

• Acivicin treatment also caused the cells to have diminished steady-state expression of messenger RNA (mRNA) for c-myc and c-myb, and increased expression of mRNA for TNF-alpha and IL-1 beta [6].
• Acivicin, which inhibits GSH breakdown by gamma-glutamyl transpeptidase (GGT), had no effect on the enhanced uptake seen during the respiratory burst [18].
• The activity is membrane-bound and is inhibited by acivicin, a known inhibitor of GGT [19].
• Acivicin inhibits GMP synthetase irreversibly by covalent modification [20].
• Furthermore, we report on the detailed characterization of the inhibition of the glutaminase domain, and thus PLP synthesis, by the glutamine analog acivicin [21].

Analytical, diagnostic and therapeutic context of acivicin

• Pharmacokinetic and biochemical studies on acivicin in phase I clinical trials [13].
• Acivicin is an investigational amino acid antitumor antibiotic currently being evaluated in Phase II clinical trials [2].
• Biochemical assessment of the effects of acivicin and dipyridamole given as a continuous 72-hour intravenous infusion [22].
• In lumen-to-bath experiments, the perfusion solution contained 4.6 microM (3)H-GSH with or without 1.0 mM acivicin [23].
• The equilibration of GSH among GSH-depleted cells and nondepleted cells in coculture was not inhibitable by acivicin, suggesting that this form of intercellular sharing of GSH does not rely on gamma-glutamyltransferase-mediated extracellular transport of GSH [24].

References