Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunohistochemical detection of multidrug resistance (MDR1) gene products and their mRNA within brain tumor cells has already been described by Fojo et al. 1987. 63 specimens of astrocytomas and glioblastomas were analysed in the present study (Grading type 1 to 4) by means of the monoclonal antibody JSB1. The endothelial cells were positive only in astrocytic tumors with a grading of 1. Increasing tumor grading resulted in more positive immunological reactions in tumor cells. The most impressive reaction could be found in anaplastic astrocytoma and glioblastoma (G3 and G4). Overexpression of this P-glycoprotein, a plasma membrane component of a relative molecular mass of 170 kDa was not only found in tumor cells of anaplastic astrocytomas, but also in endothelial cells and some non-neoplastic brain diseases. Positive immunological reactions in protoplasmatic astrocytes could be demonstrated in cases of phenylketonuria (1/1), tuberculous leptomeningitis (2/2), SSPE (3/4), X-ray necrosis (1/1) and necrotizing viral encephalitis (1/4). According to this, it seems that astrocytes are able to express P-glycoprotein under the influence of some special metabolic conditions. This underlines the detoxicating function of reactive astrocytes within the total number of cells in the CNS.
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PMID:[Expression of P-glycoprotein as a multidrug resistance gene product in human reactive astrocytes and astrocytoma]. 794 20

Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal tissues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host. The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well.
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PMID:Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. 831 77