Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Published reports indicate that normal rodent cells can grow in medium containing either L-methionine or L-homocysteine, whereas malignant rodent cells have an absolute requirement for L-methionine. Our studies with two normal human cell lines (fetal lung fibroblasts and bladder epithelial cells) exhibit equal growth in media containing either L-methionine or L-homocysteine. The same is true for five malignant human cell lines (carcinoma of the cervix [HeLa], adenocarcinoma of the breast [AlAb], acute lymphoblastic leukemia [MOLT-3], Wilms' tumor [SK-NEP-1], and reticulum cell sarcoma [T-77], whereas four other malignant cell lines (adenocarcinoma of the breast [SK-BR-2-III], the two lymphoblastic leukemias [CCRF-HSB-2 and CCRF-SB], and a neuroblastoma [SK-N-MC]) have absolute requirements for L-methionine. Two malignant cell lines, an adenocarcinoma of the lung (A549) and an adenocarcinoma of the pancreas (Capan-1), showed restricted growth under the experimental conditions used. L-Methionlinase (L-methionine-alpha-deamino-gamma-mercaptomethane-lyase, EC 4.4.1.11) at a concentration of 0.1 unit/ml leads to complete growth inhibition of cell cultures of both the normal human fetal lung fibroblasts (F-136-35-56) and the acute lymphoblastic leukemia (CCRF-HSB-2). L-Homocysteine-thiolactone in medium containing L-methioninase could partly "rescue" the normal but not the malignant cells.
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PMID:Tumor therapy by deprivation of L-methionine: rationale and results. 46 46

Methionine starvation can modulate gene methylation, cell cycle transition and pathways related to survival following DNA damage. Methionine depletion by recombinant methioninase (rMETase) may have in vitro and in vivo efficacy against neuroblastoma (NB), especially when combined with chemotherapeutic drugs. rMETase from Pseudomonas putida was produced in Escherichia coli and purified by ion-exchange chromatography. rMETase alone inhibited the proliferation of 15/15 NB cell lines in vitro. Among these 15 cell lines, only 66N demonstrated rMETase-induced apoptosis. rMETase alone suppressed LAN-1 and NMB-7 xenografts (p < 0.01) and no toxicities were noted other than reversible weight loss. In vitro efficacy experiments combining rMETase and chemotherapeutic agents were carried out using SK-N-LD and SK-N-BE (1)N established at diagnosis, as well as LAN-1, SK-N-BE (2)C and NMB-7 established at relapse. Microtubule depolymerization agents including vincristine, vinorelbine, vinblatine and mebendazole showed synergism when tested in combination with rMETase in all 5 cell lines. Among DNA damaging agents, synergy with rMETase was observed only in cell lines established at diagnosis and not at relapse. Cell cycle analysis showed that rMETase arrested G2 phase and not M phase. In vivo efficacy experiments using LAN-1 and NMB-7 xenografts showed that rMETase rendered vincristine more effective than vincristine alone in tumor growth suppression (p < 0.001). In conclusion, methionine depletion inhibited NB proliferation and arrested tumor cells at G2 phase. rMETase synergized with microtubule depolymerization agents. Moreover, synergism between rMETase and DNA damaging agents was dependent on whether cell lines were established at diagnosis or at relapse.
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PMID:Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drugs. 1908 15