Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Methionine
(
Met
) deprivation stress (
MDS
) is proposed in association with chemotherapy in the treatment of some cancers. A synergistic effect of this combination is generally acknowledged. However, little is known on the mechanism of the response to this therapeutic strategy. A model of B16 melanoma tumor in vivo was treated by
MDS
alone and in combination with chloroethylnitrosourea (CENU). It was applied recent developments in proton-NMR spectroscopy-based metabolomics for providing information on the metabolic response of tumors to
MDS
and combination with chemotherapy.
MDS
inhibited tumor growth during the deprivation period and growth resumption thereafter. The combination of
MDS
with CENU induced an effective time-dependent synergy on growth inhibition. Metabolite profiling during
MDS
showed a decreased
Met
content (P < 0.01) despite the preservation of the protein content, disorders in sulfur-containing amino acids, glutamine/proline, and phospholipid metabolism [increase of glycerophosphorylcholine (P < 0.01), decrease in phosphocholine (P < 0.05)]. The metabolic profile of
MDS
combined with CENU and ANOVA analysis revealed the implication of
Met
and phospholipid metabolism in the observed synergy, which may be interpreted as a
Met
-sparing metabolic reprogramming of tumors. It follows that combination therapy of
MDS
with CENU seems to intensify adaptive processes, which may set limitations to this therapeutic strategy.
...
PMID:Combined methionine deprivation and chloroethylnitrosourea have time-dependent therapeutic synergy on melanoma tumors that NMR spectroscopy-based metabolomics explains by methionine and phospholipid metabolism reprogramming. 1983 24
