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PubMed1986

Serum neuron-specific enolase as a marker useful for monitoring the effectiveness of therapy in patients with neuroblastoma--as compared with urinary catecholamine metabolites.

Neuron-specific enolase (NSE) in sera of 3 patients with neuroblastoma (Stage IV) were measured by radioimmunoassay, as compared with urinary catecholamine metabolites (vanillyl-mandelic acid (VMA) and homovanillic acid (HVA] during the course of chemotherapy, radiation, and second look operation. In Case 1 (Stage IV B) and Case 3 (Stage IV A), NSE-level on admission was found to be elevated to 51.0 ng/ml and 25.5 ng/ml, respectively. VMA and HVA were also elevated. In Case 2 (Stage IV A), NSE on admission was elevated to 128.0 ng/ml., HVA was high, but VMA was within normal range. From 1 to 3 weeks after chemotherapy and radiation, high levels of urinary VMA and/or HVA in patients promptly decreased within normal range. The size of primary tumor masses either showed no marked change or slightly decreased by radiological examinations. After intensive chemotherapy, high levels of serum NSE decreased within normal range. At that time, second look operations were carried out. The size of primary tumors was reduced (3.6 X 2.7 X 2.1 cm in average) and almost all masses had scarred over. These data suggest that serum NSE levels correlate very well with residual tumor burdens.

Catecholamines↗
PubMed2000

Neuron-specific enolase in hemophagocytic lymphohistiocytosis: a potential indicator for macrophage activation?

To determine the pathogenesis of hemophagocytic lymphohistiocytosis (HLH), serum levels of neuron-specific enolase (NSE) and cytokine profiles were investigated. Serum concentrations of NSE and several cytokines were measured by immunoassays, and the association was evaluated in 18 HLH patients. Serum NSE levels increased (> 10 ng/mL) in 27/29 samples (93%) during the active febrile phase, the mean level of which (35.9 ng/mL) was much higher than that during the remission phase (11.2 ng/mL) (P = .001). The peak levels of NSE in 11 patients who required cytotoxic agents were higher than those in 7 patients without chemotherapy, 64.6 +/- 49.4 and 17.9 +/- 12.9, respectively (P = .265). The NSE levels correlated positively with the levels of interferon (IFN)-gamma (Pearson's correlation coefficient [r] = 0.408, P = .044), soluble interleukin-2 receptor (sIL-2R) (r = 0.464, P = .048), lactate dehydrogenase (r = 0.830, P < .00001), aspartate aminotransferase (r = 0.531, P = .003), and ferritin (r = 0.715, P < .00001), and correlated negatively with platelet count (r = -0.422, P = .021), but not with other parameters, including tumor necrosis factor-alpha, IL-1 beta, IL-18, soluble Fas ligand and C-reactive protein. Multiple regression analysis indicated that the correlation of NSE with platelet count was independent of other correlations. Sequential NSE changes well reflected the clinical course of patients. Immunohistochemical staining revealed an appreciable number of NSE-positive histiocytes in bone marrow specimens with florid hemophagocytosis. These results suggest that the circulating NSE originated from macrophages stimulated with IFN-gamma/sIL-2R, and partly from the destruction of platelets. Serum NSE level may be a useful marker for predicting the disease progression of HLH.

Adolescent↗
PubMed2006

Blood metallothionein, neuron specific enolase, and protein S100B in patients with traumatic brain injury.

OBJECTIVES: The aim of this study was to evaluate the correlation of neuron specific enolase (NSE), protein S100B and time-profile of Glasgow Coma Score (GCS) development with metallothionein (MT) blood levels in patients with traumatic brain injury (TBI) during 10 days of hospitalization. Patients were divided into 2 groups with respect to NSE and S100B levels - with (group I) and without (group II) GCS improvement. METHODS: Serum NSE and S100B concentrations were measured by immunochemical methods; serum metallothionein concentration by electrochemical technique. Cortical biopsies were investigated immunohistochemically and by electron microscope. A cDNA microarray containing 700 gene probes was used to study the changes in gene expression in the ipsilateral cortex. RESULTS: Values of MT in the blood of group I showed a non-significant decrease compared to group II during 1-3 days after admission. There was an increase of MT during 4-8 days in comparison with values of 1-3 days. The highest value of MT during hospitalization was found in a patient with diffuse axonal injury (group II). The data of cDNA microarray suggested an increase in expression of gene transcripts for oxygen free radical scavenger proteins corresponding with the increase of MT during 4-8 days in both groups. CONCLUSIONS: The experimental data indicate that monitoring the content of MT in patients with trauma brain injury would be a suitable approach to evaluate the degree of injury or duration of prolonging unconsciousness, particularly in diagnosis of diffuse axonal injury.

Brain Injuries↗
PubMed1988

Neuron-specific enolase in the diagnosis of small-cell lung cancer with pleural effusion: a negative report.

We measured the concentration of neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) in the serum and pleural fluid of 53 patients with pleural effusions, including seven patients with small-cell lung cancer (SCLC). High levels (above 12.5 micrograms.l-1) of NSE in pleural fluid were observed in five patients with SCLC (sensitivity 71%). However, pleural fluid NSE levels were also increased in five patients with other types of cancer and in four patients with non-malignant inflammatory diseases (specificity 80%). We conclude that although SCLC with pleural effusion can be associated with elevated pleural fluid NSE activity, this increase in enzyme levels is not specific for malignancy.

Aged↗
PubMed1987

Doubling time of neuron-specific enolase and survival in small cell lung cancer patients. Results of a preliminary analysis.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Carcinoma, Small Cell↗
PubMed1995

A comparison of the prognostic value of neuron-specific enolase serum levels and somatosensory evoked potentials in 13 reanimated patients.

Thirteen patients resuscitated after circulatory arrest due to cardiopulmonary aetiologies were studied with regard to survival and outcome. Exclusion criteria were known central nervous system disorders or death secondary to cerebrovascular accident. The serum level of neuron-specific enolase (NSE), presumably a reliable marker of neuronal death, was measured by enzyme immunoassay in peripheral blood samples over the course of 4 days at 12 h intervals. On the first and third day post-resuscitation, median nerve somatosensory evoked potentials (SSEPs) were recorded and evaluated for the absence of the cortical potential--presently the standard approach for assessing prognosis in terms of post-resuscitation hypoxaemic brain damage. Absent cortical potentials were found in six patients with NSE levels above 140 micrograms l-1. Five of these patients died; one patient survived with loss of cortical functioning. Five patients had normal SSEP findings, and their NSE maximum levels were below 25 micrograms l-1. All five patients survived without neurological deficits. One patient with a peak NSE level of 36 micrograms l-1 on the second day developed a prolonged delirium (according to DSM III-R criteria) and one patient with a peak level of 76 micrograms l-1 on the fourth day developed an acute respiratory distress syndrome; both patients had preserved cortical potentials. In conclusion, pathological SSEPs and increased NSE levels are of comparable prognostic value. They may well be complementary investigations. The neuron-bound enzyme NSE is a biochemical marker which varies with the extent of neuronal damage, while absence of the cortical potentials may indicate neurophysiological loss of function.

Aged↗
PubMed1990

Development of a radioimmunoassay for neurone specific enolase (NSE) and its application in the study of patients receiving intra hepatic arterial streptozotocin and floxuridine.

A radioimmunoassay has been developed for neurone specific enolase (NSE) and used to measure serum NSE levels in patients with neuroendocrine and non-neuroendocrine tumours following intra hepatic arterial chemotherapy. Ten patients were studied, 7 receiving streptozotocin and floxuridine for neuroendocrine tumours and three receiving cisplatinum for non-neuroendocrine neoplasms. All ten patients had liver metastases. In patients with tumours of neuroendocrine origin, a significant increase in serum NSE was recorded within 24 h of therapy. Slight increases in serum NSE levels were also recorded in three patients with non neuroendocrine tumours. These increases may reflect lysis of neuroendocrine cells within the tumour. Raised levels in non-neuroendocrine tumour patients may reveal damage done to healthy neuronal and neuroendocrine cells during treatment. NSE may be a useful marker of the extent of cell death following chemotherapy.

Animals↗
PubMed1982

Neuron specific enolase: a marker for differential diagnosis of neuroblastoma and Wilms' tumor.

Thirteen human neuroblastoma and six Wilms' tumor biopsies have been analyzed for neuron specific enolase (NSE). THe relative activity of NSE in the neuroblastomas (including ganglioneuroblastoma and ganglioneuroma) ranged from 28% to 62.5% of total enolase activity. The corresponding figures for the Wilms' tumors were 1% to 4.5%. It appears that NSE can serve as a biochemical marker for neuroblastoma and be useful in the differential diagnosis of neuroblastoma and Wilms' tumor.

Child↗
PubMed1987

Localization of neuron-specific enolase (NSE) mRNA in human brain.

In situ hybridization with biotinylated DNA and RNA probes derived from the 3' untranslated region of human neuron-specific or gamma gamma-enolase (NSE) permits histochemical detection of NSE mRNA in autopsy samples of human brain. In both aged controls and Alzheimer's disease (AD) patients, NSE probe hybridized with variable intensity to nerve cells in visual cortex and cerebellum, but not to glial or liver cells. These results provide evidence that NSE mRNA is expressed in neurons in human brain tissue, pattern of NSE mRNA expression in unaffected brain regions in AD is qualitatively normal, and NSE mRNA expression may vary widely among different classes of neurons.

Adult↗
PubMed1995

Cerebrospinal fluid levels of S-100b protein and neuron-specific enolase in chronic inflammatory demyelinating polyneuropathy.

We measured the cerebrospinal fluid (CSF) concentrations of S-100b protein (S-100b) and neuron-specific enolase (NSE) using enzyme immunoassay methods in 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), other three patients with chronic neuropathy with demyelination, eight patients with various axonal neuropathies (AN), and 46 controls, to investigate the clinical usefulness of the determination of these two specific proteins in these neuropathies. S-100b levels were elevated (> the mean +/- 2 SD levels of controls) in the majority of patients with clinically progressing CIDP (9/11), but not in the patients with AN (0/8). In parallel with the clinical improvement, S-100b levels were normalized in patients with CIDP (10/10), though total protein levels in the CSF still remained high in some of these patients (5/10). Elevation of NSE levels were seldom seen in clinically worsening patients with CIDP (1/11) or AN (1/8). Thus our results indicated that the level of S-100b in the CSF may be useful to assess the activity of actual disease process in CIDP.

Adolescent↗
PubMed1990

Usefulness of immunocytochemical demonstration of neuron-specific enolase in the diagnosis of Hirschsprung's disease.

The work reported here was carried out to study the importance of immunocytochemical staining of neuron-specific enolase (NSE) in the diagnosis of Hirschsprung's disease and to compare its results with those obtained by hematoxylin-eosin (H&E) staining in consecutive sections. A retrospective study was made on 51 rectal mucosal biopsies and 19 colorectal surgical specimens from 52 patients clinically suspected of Hirschsprung's disease. Several consecutive sections from all cases were restained by H&E and for NSE demonstration. Sixteen (31%) patients had a histological diagnosis of Hirschsprung's disease, 9 (17%) had hypoganglionosis, 4 (8%) had neuronal intestinal dysplasia, and 2 (4%) had normal histology. In eight patients (15%) hypoganglionosis remained dubious, and in 10 (19%) the diagnosis was inconclusive. Although the NSE staining improved the identification of the nervous tissue of the colon, both H&E and NSE staining proved to be of equal value in the assessment of the presence of neurons in the rectal wall of people with clinically suspected cases of Hirschsprung's disease. Ten H&E-stained sections from different levels of the biopsy specimen would be enough to detect ganglion cells in most cases.

Adolescent↗
PubMed1982

Neuron specific in vitro cytotoxicity of sera from patients with amyotrophic lateral sclerosis.

Sera from patients with amyotrophic lateral sclerosis (ALS) were assayed for a neuron-specific cytotoxic effect on long-term organized cultures of neonatal mouse anterior horn segments. Blind studies show that ALS sera when incorporated into the culture media have a greater degree of antineuronal toxicity than sera from patients with other neurological diseases or from family members of ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter.

Adenoviruses are highly efficient vectors for gene transfer into brain cells. Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for gene therapy in the central nervous system. We targeted gene expression to neurons by constructing an adenoviral vector that expressed the E. coli LacZ reporter gene under the control of the rat neuron-specific enolase promoter (Ad-NSE). Expression from Ad-NSE was compared with that from an adenoviral vector encoding the same reporter gene under the control of the Rous sarcoma virus LTR promoter (Ad-RSV). Both recombinant adenoviruses were injected stereotactically into rat hippocampus, cerebellum and striatum. Anatomical and immunohistochemical analyses of the Ad-NSE-stained cells showed that neurons were preferentially transduced. More neurons were stained in the hippocampus following infection with Ad-NSE than with Ad-RSV. Cytotoxicity from Ad-NSE was lower than from Ad-RSV. beta-Galactosidase gene expression after Ad-NSE infection remained stable for 3(1/2) months, and was detectable for 6 months. Thus, the NSE-adenoviral vector can be used to transfer potentially therapeutic genes into neuronal cells. The use of a cell-specific promoter also resulted in high in vivo efficiency and long-term transgene expression.

Adenoviridae↗
PubMed1991

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase.

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.

Antibodies, Monoclonal↗
PubMed1993

Immunohistochemical demonstration of neuron specific antigen, HPC-1 in the enteric nervous system of the guinea-pig distal colon.

The HPC-1 antigen is a newly identified neuron specific membrane protein in the central nervous system. The HPC-1 antigen was revealed similarity to epimorphin. The presence of HPC-1 antigen in the enteric nervous system of guinea-pig distal colon was immunohistochemically demonstrated using the antibody against the HPC-1. Immunohistochemical study clearly revealed the topography and structure of the enteric nervous system of the guinea-pig distal colon. HPC-1 was present only in the nervous system and entirely distributed. HPC-1 antigen is present at the surfaces of ganglion cells, but not in the cytoplasm.

Animals↗
PubMed2000

[Radioimmunometric assay of neuron specific enolase in aqueous humor and serum in patients with retinoblastoma].

INTRODUCTION: Retinoblastomas (RB) are the most common malignant intraocular tumors in childhood. The neuron specific enolase (NSE) is used as a tumor marker in different malignant diseases (mainly in neuroblastomas and lung carcinoma of small cells). In this work we report our experience using NSE and the role we consider that it plays in the determination of this enzyme in RB cases. MATERIALS AND METHODS: NSE determinations in aqueous humor (AH) and serum were carried out in 17 RB by means of a radioimmunometric assay and were compared with those values obtained in a control group composed of 8 subjects in whom the RB diagnosis as well as other diseases that could alter its determination had been ruled out. The possible correlation between NSE levels and different tumor stages (Reese-Elsworth and histological-clinical), as well as the tumor type (exophytic and mixed) were also studied. RESULTS: NSE levels were increased in AH and serum in 88% of RB patients and were normal in all the subjects in the control group (when a sample which was considered to be non-valid due to the presence of red cells in AH was excluded). No correlation between NSE levels in AH and serum and the different tumor stages was found. Nevertheless, the RB group of mixed tumor type showed a significantly higher mean in AH (p<0.01) than the RB exophytic group. CONCLUSION: NSE determination in AH is of value in the differential diagnosis in patients in whom RB is suspected but difficult to diagnose as well as in the diagnosis of relapses. Serum determinations are mainly useful in the follow-up and in the early diagnosis of possible metastases.

Child, Preschool↗
PubMed1993

Expression of c-erbB-2 protein, neuron-specific enolase and DNA flow cytometry in locally advanced transitional cell carcinoma of the urinary bladder.

Expression of c-erbB-2 protein, neuron-specific enolase (NSE) and DNA ploidy was studied by immunohistochemistry and flow cytometry in formalin-fixed and paraffin-embedded specimens from 104 patients with locally advanced transitional cell carcinoma of the bladder. Positive membrane bound c-erbB-2 staining was found in 15% of the tumours, and 38% of the tumours were positive for NSE. Only one tumour stained positively for both NSE and c-erbB-2. Expression of c-erbB-2 protein and NSE was neither correlated to tumour stage nor to histopathological grade. The frequency of non-diploid tumours was 78% in 49 c-erbB-2/NSE negative tumours, 98% in 40 NSE positive tumours, and 100% in 16 c-erbB-2 positive tumours (P = 0.004). Whether the c-erbB-2 expression is a useful prognostic marker in addition to other conventional parameters, remains to be shown.

Antineoplastic Agents↗
PubMed2000

Serum neuron-specific enolase as a predictor of intracranial lesions in children with head trauma: a pilot study.

OBJECTIVE: To determine the reliability of serum neuron-specific enolase (NSE) levels in predicting intracranial lesions (ICL) in children with blunt head trauma (HT). METHODS: A prospective pilot study was conducted of patients 0 to 18 years of age presenting to a children's hospital emergency department (ED) between December 1997 and October 1998. Children presenting within 24 hours of injury who required head computed tomography (CT) were eligible. Blood samples were obtained to measure serum NSE level. Data collected included patient demographics, historical information, Glasgow Coma Scale score (GCS), physical examination, head CT results, and outcome. Patients were assigned to one of two groups based on the head CT results (PICL; presence of intracranial lesion, or NICL; no intracranial lesion). Data were analyzed using Student's t-test and chi-square. The 95% confidence interval (95% CI) was calculated when appropriate. A receiver operating characteristic curve was constructed to determine the NSE level that yielded the highest sensitivity and specificity for predicting ICL. RESULTS: Fifty patients were enrolled; 22 (45%) had abnormal head CT. No difference in demographics or mechanism of injury was observed between those with abnormal or normal CT scans. The mean GCS level was 11.9 +/- 4.2 for PICL and 13.9 +/- 2.6 for NICL (p = 0.045; 95% CI = -0.05 to -3.9). The mean NSE level was 26.7 +/- 21.4 for PICL and 17.7 +/- 7.8 for NICL (p = 0.048; 95% CI = 0.1 to 17.9). An NSE level > or = 15.3 ng/mL yielded a sensitivity of 77%, a specificity of 52%, and a negative predictive value of 74%. CONCLUSIONS: These results suggest that serum NSE may be a useful screening tool for predicting ICL in children with blunt head trauma. However, the NSE alone was neither sensitive nor specific in predicting all patients with ICL.

Adolescent↗