desmosterol and Glioma

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Desmosterol; Glioma; Humans; Radioimmunoassay

The hypocholesterolemic agent 3 beta-(2-diethylaminoethoxy)androst-5-en-17-one . HCl (U18666A) is known to induce experimental epilepsy. The possibility that this drug interferes with cholesteryl ester formation in glioblastoma cells was examined. The incorporation of radioactive oleic acid into cellular cholesteryl ester was drastically and specifically inhibited by U18666A. The inhibitory effect of U18666A persisted in different oleic acid concentrations. Kinetic studies revealed the rapidity of U18666A action. U18666A was found to be ineffective in inhibiting acyl-CoA:cholesterol acyltransferase activity when it was added directly to the cell homogenates. In contrast, the acyltransferase activity was greatly diminished in homogenates derived from U18666A-treated cells. Thus, U18666A appeared to block cellular cholesteryl ester biosynthesis by indirectly inactivating acyl-CoA:cholesterol acyltransferase activity in a cell-dependent manner. The potent inhibition of cholesteryl ester formation by U18666A represents one unique aspect of the drug which might contribute to its ability to induce chronic epileptiform activity.

Topics: Androstenes; Animals; Anticholesteremic Agents; Cell Line; Cholesterol Esters; Desmosterol; Glioma; Ketocholesterols; Neuroglia; Oleic Acid; Oleic Acids; Rats; Squalene; Sterol O-Acyltransferase; Time Factors

Topics: Astrocytoma; Brain Neoplasms; Carmustine; Cholesterol; Chromatography, Gas; Desmosterol; Diagnosis, Differential; Ependymoma; Glioma; Humans; Lomustine; Medulloblastoma; Oligodendroglioma; Triparanol

This study was an effort to obtain a marker indicative of the biologic activity of human gliomas. Sterol levels in the cerebrospinal fluid (CSF) were evaluated. Studies were conducted longitudinally during the course of tumor therapy. The evidence indicated that desmosterol levels in the CSF may reflect the growth potential of these neoplasms.

Topics: Adult; Aged; Brain Neoplasms; Cholesterol; Desmosterol; Glioma; Humans; Male; Middle Aged; Triparanol

Topics: Blood-Brain Barrier; Brain Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Desmosterol; Female; Glioma; Humans; Muramidase; Neoplasm Metastasis; Pregnancy

Topics: Adult; Astrocytoma; Brain Neoplasms; Carmustine; Cholesterol; Desmosterol; Female; Glioma; Humans; Infant; Lomustine; Male; Middle Aged; Nitrosourea Compounds; Oligodendroglioma

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Topics: Animals; Astrocytoma; Brain Neoplasms; Cells, Cultured; Cholesterol; Desmosterol; Fibroblasts; Glioma; Humans; L Cells; Neoplasms, Experimental; Neurilemmoma; Rats

Desmosterol (5, 24-cholestadien-3beta-ol; delta 24-cholesterol; 24-dehydrocholesterol), an immediate precursor of brain cholesterol, increased in malignant intracranial tumors induced in rats by nitrosourea derivatives. The average increase in desmosterol was higher in intracerebral gliomas than in neurinomas of the trigeminal nerve. Similarly, desmosterol increased only slightly in developing normal trigeminal nerve compared to the high levels observed in developing cerebrum. The differences may have been partly related to the predominantly growing cell type, i.e., glial (central nervous system) or Schwann (peripheral nervous system) cells seen at the time of study.

Topics: Age Factors; Animals; Brain Neoplasms; Carcinogens; Cholesterol; Desmosterol; Female; Fetal Diseases; Gestational Age; Glioma; Neoplasms, Experimental; Neurilemmoma; Nitrosourea Compounds; Peripheral Nervous System Neoplasms; Pregnancy; Rats; Rats, Inbred Strains; Trigeminal Nerve

Topics: Animals; Astrocytoma; Brain Neoplasms; Cholesterol; Chromatography, Gas; Culture Techniques; Desmosterol; Glioblastoma; Glioma; Humans; Methotrexate; Oligodendroglioma; Rats; Sterols; Triparanol

Topics: Animals; Brain; Brain Neoplasms; Desmosterol; DNA; DNA, Neoplasm; Ependymoma; Female; Glioma; Neurilemmoma; Nitrosourea Compounds; Oligodendroglioma; Rats; RNA; RNA, Neoplasm; Sarcoma; Spinal Cord Neoplasms; Thymidine