1. Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children
- Author
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Lili Mikecin, Miroslav Gjurasin, Josipa Kern, Jasna Leniček Krleža, Ljiljana Popović, Jasminka Stepan Giljević, and Miljenko Križmarić
- Subjects
Male ,Brain and Mental Health ,medicine.medical_specialty ,Pathology ,Adolescent ,Central nervous system ,Biology ,Sensitivity and Specificity ,Central Nervous System Neoplasms ,White matter ,chemistry.chemical_compound ,Cerebrospinal fluid ,Internal medicine ,Glioma ,Biomarkers, Tumor ,medicine ,Humans ,Child ,Pseudocholinesterase ,central nervous system tumors ,cerebrospinal fluid ,child ,medicine.diagnostic_test ,Lumbar puncture ,General Medicine ,Spinal cord ,medicine.disease ,Acetylcholinesterase ,Endocrinology ,medicine.anatomical_structure ,ROC Curve ,chemistry ,Butyrylcholinesterase ,Case-Control Studies ,Child, Preschool ,Biomarker (medicine) ,Female - Abstract
Pediatric solid central nervous system (CNS) tumors are rarely detected at an early stage. The reasons for this include the tumor site, acute intracranial bleeding, unavailable imaging tests, inconsistent conduct of clinical diagnostic procedures, etc (1). CNS tumors account for 20% of all childhood cancers, and their incidence rates are rising (2). Treatment results are better if the disease is detected early, which requires sufficiently sensitive and specific diagnostic methods. This is why new biomarkers indicating the presence of CNS tumors are needed. One of the biological materials used for biomarker testing is cerebrospinal fluid (CSF) (3). CSF washes the structures of the CNS including the tumors present there, enabling the detection of tumor proteins in the CSF. PChE has a role in tumorogenesis and oncogenesis and has been proven to be a good indicator of the presence of tumors (4-6). PChE in serum has already been recognized and confirmed as a good diagnostic and prognostic marker for head and neck tumors (7). Studies of PChE in tumor tissue showed that its concentration in some tumor samples was high, eg, in glioma tissue samples (4). In tissue samples, PChE has higher activity levels in astrocytomas than in meduloblastomas, neuromas, or meningeomas (4). It is included in the myelin metabolism of, eg, the corpus callosum, nervus opticus, and spinal cord. Subcortical white matter has much greater PChE activity than gray matter (8) and PChE activity decreases as we descend from the cerebrum toward the spinal cord. After blood removal, PChE activity is present in the vessels of the brain and it is higher in arteries than in veins (4) PChE is an enzyme (EC 3.1.1.8) synthesized in the liver and distributed to body tissue and fluids. Cholinesterases (acetylcholinesterase – AChE and PChE) activity changes in an abnormal tissue metabolism and/or they become part of the oncogenic process (7). Cholinesterase genes are amplified, aberrant, and mutated in numerous types of human tumors. The PChE and AChE found in these tumors contain the peptide motif S/T-P-X-Z found in many cdc2 gene-dependent protein kinase substrates (5). Phosphorylation of cdc2-dependent protein kinases is a possible molecular mechanism that connects cholinesterases with tumor proliferation. Moreover, the inhibition or reduction of AChE, PChE, and some other enzymes especially with organophosphorous and perhaps carbamate poisons used as insecticides in home and local environment may result in the formation of brain tumors in children partially depending on the genetic polymorphisms that affect insecticide metabolism (9,10). PChE activity in CSF in healthy people is rarely investigated, most often as a part of studies on specific diseases or anesthetics (11-13). Lumbar puncture is an invasive procedure and for ethical reasons the number of healthy participants in studies is always small, especially in case of children. For this reason the information about the normal values of PChE activity in CSF in relation to age at all ages is scarce. In adults, PChE activity in CSF ranges from 1/20 to 1/100 of the value of serum (13). In children, the values are age-dependent (14). PChE activity in serum is low at birth, which is followed by a sudden increase in activity over the next three weeks, with values exceeding those in adulthood. This remains unchanged until the age of three. Between three and six years, PChE activity is 30% above the adult level and it begins to slowly drop between the age of five and puberty, when it reaches the adulthood value, which remains relatively stable (14). In this study, we tested whether PChE could be used as a potential biomarker for solid CNS tumors in children.
- Published
- 2013
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