Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two anorectic, emaciated infants with central nervous system (CNS) neoplasms are reported. Diagnosis in each case was delayed, because computed tomography of the head was initially falsely negative, and because primary gastroenterologic illness was suggested by the presence of mild inflammation and villous atrophy of the small intestine. This experience indicates that the diagnosis of CNS neoplasm must be aggressively pursued in cachectic infants who refuse to eat, regardless of the results of the initial radiologic studies. Mild histologic abnormalities of the small intestine that may be present in infants with brain tumors probably represent a nonspecific response to starvation and, if unassociated with malabsorption, should not be considered the cause of illness.
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PMID:Intestinal abnormalities with central nervous system malignancy. 373 19

Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.
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PMID:Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma. 2332 65