desmosterol and Brain-Neoplasms

In clinical practice, the examination of cerebrospinal fluid from patients with primary or metastatic brain tumors is commonly limited to cytomorphologic and routine chemistry analysis. The relative lack of sensitivity and specificity of these tests has led to a search for markers that can detect nervous system involvement by neoplasms at an earlier stage and even predict the site of origin of the neoplasms. This article summarizes recent investigators of biochemical tumor markers and cytoplasmic and cell surface markers in cerebrospinal fluid from patients with nervous system tumors.

Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, Neoplasm; beta 2-Microglobulin; Brain Neoplasms; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Desmosterol; Glial Fibrillary Acidic Protein; Glucuronidase; Humans; Immunoglobulins; L-Lactate Dehydrogenase; Lymphocytes; Neoplasm Proteins; Peptide Fragments; Pituitary Hormones; Polyamines

The concept of tumor markers was reviewed, and the potential uses of markers of central nervous system (CNS) tumors and methods for their evaluation were discussed. Markers examined included lactate dehydrogenase, aspartate aminotransferase, fructose-bisphosphate aldolase, the polyamines, desmosterol, and several other enzymatic, nonenzymatic, and immunologic markers. Data collated from the clinical studies surveyed showed isocitrate dehydrogenase, desmosterol, and the polyamines to have the greatest potential utility in the diagnosis of CNS tumors.

Topics: Antigens, Neoplasm; Aspartate Aminotransferases; Brain Neoplasms; Desmosterol; Fructose-Bisphosphate Aldolase; Humans; L-Lactate Dehydrogenase; Polyamines; Research Design

Topics: Animals; Anticholesteremic Agents; Brain; Brain Neoplasms; Cholesterol; Desmosterol; Glycolipids; Humans; Lipid Metabolism; Lipids; Mevalonic Acid; Nerve Tissue; Peripheral Nerves; Peripheral Nervous System Neoplasms; Pharmacology; Phospholipids; Sterols; Time Factors; Triparanol

The desmosterol test for the diagnosis of central nervous system (CNS) tumors is proposed in a simplified form. The procedure is based upon the analysis of sterol profile in cerebrospinal fluid (CSF) by selected ion monitoring (SIM) technique. Applied to 55 patients with tumoral and non tumoral CNS disease, the new test detects average levels of CSF desmosterol in tumor bearing patients that are tenfold higher than in the absence of CNS neoplasia. On an individual basis, a concentration of CSF desmosterol equal to or higher than the mean plus twice the standard deviation for the reference group of patients with no CNS tumor, is considered a positive result. Based on this criterion, a correct diagnosis was made in 73% of cases vs 77% of the former test, which required a 5-day treatment period with a desmosterol-reductase inhibitor in order to increase CSF desmosterol concentration. With this revised procedure CSF desmosterol can be detected in smaller volumes of CSF without any drug pretreatment, thus making the test more suitable for clinical application.

Topics: Brain Neoplasms; Chromatography, Gas; Desmosterol; Evaluation Studies as Topic; Humans; Ions; Mass Spectrometry; Methods

Biological markers of tumors are compounds or enzymatic activities measurable in body fluids. Their presence or concentration must be linked to tumoral growth. The markers of the central nervous system tumors are detected in CSF. Alpha-feto-protein, carcinoembryonic antigen, human chorionic gonadotropin, adenohypophyseal peptide hormones, enzymes, etc., have found some application in the early diagnosis of leptomeningeal metastasis. Other applications involve the early detection and recurrency of primary brain tumors, as well as the evaluation of efficacy of their therapy. The tests based on the CSF content of desmosterol and polyamines have been studied extensively. Their rationale is discussed and specificity, sensitivity, efficiency and predictive value are considered. Experimental results concerning a new possible biochemical marker, based on CSF concentration of cyclic adenosine monophosphate, are reported.

Topics: alpha-Fetoproteins; Brain Neoplasms; Carcinoembryonic Antigen; Cerebrospinal Fluid; Desmosterol; Diagnostic Errors; Humans; Nucleotides, Cyclic; Polyamines

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

The cerebrospinal fluid levels of cholesterol, desmosterol, and the ratio 100 D:C taken from a study of 59 patients are reported. The patients, who had tumors of the nervous system, underwent neurosurgery, radiotherapy, and chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea or 1-(2-chlororethyl)-3-cyclohexyl-1-nitrosourea. The relationships among the levels of these three parameters and the clinical and neuroradiologic evolution are discussed.

Topics: Adult; Antineoplastic Agents; Brain Neoplasms; Carmustine; Cholesterol; Desmosterol; Female; Humans; Lomustine; Male; Middle Aged

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

The composition and distribution of steryl esters in human diseased or developing brain tissue has been studied. The abnormal brain conditions included sudanophilic leukodystrophy, multiple sclerosis plaque, subacute sclerosing panencephalitis, and an old cerebral infarction and two types of brain-derived tumors. In addition to the above abnormal tissue, steryl esters were also examined in developing and normal adult human brain. It was found upon subcellular fractionation that the steryl ester was localized mainly in the soluble nonparticulate material. A cholesteryl ester-rich fraction, floating on top of distilled water after centrifugation, was recovered only in the developing brain or in instances where there was myelin damage. The sterol portion of the steryl ester was largely cholesterol. The fatty acid moiety was mainly composed of C(16), C(18), and C(20) fatty acids. The dominant fatty acid was oleic acid, and the proportion of this fatty acid increased in demyelination. Although there were great differences in the quantities of steryl ester found, the fatty acid profiles of normal developing and adult brain were quite similar. As has been noted by others, the fatty acid composition of brain steryl esters most closely resembles that of brain phosphatidylcholine.

Topics: Adult; Brain; Brain Neoplasms; Cholesterol; Chromatography; Chromatography, Gas; Corpus Callosum; Desmosterol; Esters; Fatty Acids; Humans; Infant; Infant, Newborn; Infarction; Lanosterol; Leukodystrophy, Metachromatic; Multiple Sclerosis; Neurilemmoma; Oligodendroglioma; Silicon Dioxide; Sterols; Subacute Sclerosing Panencephalitis; Subcellular Fractions

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

Topics: Acute Disease; Astrocytoma; Autoanalysis; Brain Neoplasms; Cholestanes; Cholesterol; Chromatography, Gas; Desmosterol; Esters; Evaluation Studies as Topic; Follow-Up Studies; Glioblastoma; Humans; Methods; 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