Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral effects of 6-diazo-5-oxo-L-norleucine (L-DON) on the replication of human parainfluenza virus type 2 (HPIV-2), mumps and vesicular stomatitis viruses were studied. L-DON suppressed growth of these viruses and, in particular, HPIV-2 in four cell types. L-DON was not toxic to the cells at the active dose and did not significantly inhibit cellular macromolecular synthesis. The L-DON-sensitive step of HPIV-2 replication was considered to be relatively early. The NP, P and M proteins were, although at a low level, clearly detectable in HPIV-2-infected Vero cells treated with L-DON, whereas the HN and F proteins were scarcely detected by either immunostaining or immunoprecipitation, indicating that L-DON mainly decreased the amounts of viral glycoproteins. Furthermore, Northern blot hybridization showed that secondary transcription of virus RNA was also inhibited.
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PMID:Antiviral effect of 6-diazo-5-oxo-L-norleucine, antagonist of gamma-glutamyl transpeptidase, on replication of human parainfluenza virus type 2. 196 85

Ninety-eight patients with previously-treated advanced soft tissue sarcoma, bone sarcoma, or mesothelioma were randomly assigned to one of two intravenous single-agent treatment regimens, either 6-diazo-5-oxo-l-norleucine (DON; brief infusions of 50 mg/m2/day for 5 consecutive days every 4 weeks) or aclacinomycin-A (ACM-A, as 30-min infusions of 100 mg/m2 or 85 mg/m2, administered every 3 weeks). Of 43 patients who were evaluable for response, survival and toxicity, there were two responses (5%) produced by ACM-A; one in a male with mesothelioma, and one in a female with malignant fibrous histiocytoma. None of the 36 evaluable patients treated with DON developed an objective tumor response. Median survival was 4.8 months in the DON treatment arm, and 6.8 months in the ACM-A treatment arm. No patients on the DON arm experienced lethal or life-threatening toxicities, and severe toxicities resulting from this treatment included nausea and emesis (10%), stomatitis (2%), gastrointestinal toxicity (2%), and anemia (2%). Moderate toxicities included vomiting (24%), hematologic toxicity (24%), neurologic toxicity (7%), diarrhea (7%), mucositis (5%), fever (5%), palpitations (2%), hepatotoxicity (2%), bleeding (2%) and edema (2%). Fifteen percent experienced at least one severe reaction, and 63% experienced at least one moderate or greater toxicity. ACM-A was associated with four cases of life-threatening myelosuppression (7%); severe toxicities included myelosuppression (11%), neurologic toxicity (4%), diarrhea (2%), respiratory toxicity (2%), pain and muscle spasms (2%), edema (2%), and ulceration following extravasation (2%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas. 218 26

The effects of 6-diazo-5-oxo-L-norleucine (DON), 2-deoxy-D-glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined. During a 48-hr replication period, TM, DON, and DOG inhibit VSV plaque formation in HEp-2 cells by 99.9%, 99.8%, and 99.9% respectively. Inhibition of VSV by DON is reversed with glutamine. Although all three agents are known to affect glycoprotein synthesis, DON and DOG also inhibit plaque formation of viruses devoid of structural glycoproteins. Thus, plaque formation of PV types 1 and 3 and Coxsackie B3 virus is delayed in HEp-2 and Buffalo green monkey kidney cells during exposure to these agents. Since these viruses do not contain glycoproteins and since concentrations up to 10 micrograms TM/ml cause no significant inhibition of PV, DON and DOG are affecting another viral or cellular process. Inhibition of PV replication by DON is reversed by addition of 25 mM glutamine or marginally by exposure to a combination of 5 mM concentrations of cytidine, uridine, adenosine monophosphate, and guanosine monophosphate. Inhibition of PV replication by DOG is reversed with 5 mM uridine alone. During DON exposure of HEp-2 cells infected with PV, the amount of 3H-uridine incorporation at 5.5 hr postinfection (pi) is reduced to 53% of untreated controls, an amount 11% greater than incorporation in cultures infected with PV but not treated with DON. These data indicate that the inhibition of PV replication by DON or DOG occurs at the level of viral RNA synthesis, while the primary target of these agents during VSV replication is probably glycosylation.
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PMID:Poliovirus and vesicular stomatitis virus replication in the presence of 6-diazo-5-oxo-L-norleucine or 2-deoxy-D-glucose. 620 20

6-Diazo-5-oxo-L-norleucine (DON), an L-glutamine antagonist, was administered to 25 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 58 evaluable courses of five daily iv injections every 3-4 weeks were given, at doses ranging from 7.5 to 90 mg/m2/day. The major dose-limiting toxicity was a syndrome of nausea, vomiting, malaise, and anorexia, which became severe at doses greater than 52.5 mg/m2/day. Diarrhea and stomatitis were less frequent. Hematologic toxicity included mild leukopenia with nadir on Day 6-8 and mild thrombocytopenia with nadir on Day 7-12. Transient decreases in serum calcium to 8.5--8.9 mg/dl were seen in seven of 12 patients receiving greater than or equal to 67.5 mg/m2/day. Dose reduction was required for all patients who received a course of DON at greater than 67.5 mg/m2/day, and a maximum tolerated total dose of 250 mg/m2 (50 mg/m2/day x 5) is suggested for this schedule. Mixed responses were seen in one patient with bladder carcinoma and in one with pulmonary adenocarcinoma.
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PMID:Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses. 708 23

An L-glutamine antagonist, 6-diazo-5-oxo-L-norleucin (L-DON), inhibits replication of vesicular stomatitis virus, poliovirus and paramyxoviruses in cultured cells. We tested the antiviral activity of L-DON against different strains of herpes simplex virus type 1 (HSV-1) in Vero cells. In the presence of a physiological plasma concentration of L-glutamine (0.5mM) L-Don inhibited 50% production of virus plaques at concentrations ranging from 7.9 to 16 microM. At concentrations of 40 microM L-Don inhibited infectious virus yield by 99%. The antiviral activity of L-DON decreased with increasing L-glutamine concentrations. A concentration of 5000 microM of L-Don had no significant effects on the viability of Vero cells. Transmission electron microscopical investigations showed that L-DON prevented mainly envelopment of viral nucleocapsids in the cytoplasm. The immunoprecipitation experiments demonstrated selective inhibition of synthesis of HSV-1 glycoproteins in L-DON treated cells. The results showed that L-DON inhibits HSV-1 replication at a late stage in the virus replication cycle, probably the cytoplasmic maturation of virions and subsequent virion egress from the cells.
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PMID:Antiviral effects of 6-diazo-5-oxo-L-norleucin on replication of herpes simplex virus type 1. 903 73