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PubMed1999

Neuron-specific enolase, thymidine kinase, and tissue polypeptide-specific antigen in diagnosis and response to chemotherapy of small-cell lung cancer.

The clinical usefulness of neuron-specific enolase (NSE), thymidine kinase (TK), and tissue polypeptide-specific antigen (TPS) was investigated in 41 patients (53-80 years old) with recently discovered small-cell lung cancer (SCLC). Eleven patients exhibited limited disease (LD) and 30 extensive disease (ED). Serum samples for NSE, TPS (immunoradiometric assay), and TK (radioenzymatic assay) evaluations were drawn from all patients at the time of diagnosis and before each cycle of chemotherapy in the treated patients. Therapy consisted of i.v. carboplatin 300 mg/m2 on the first day and i.v. etoposide 120 mg/m2 from the first to the third day every 3 weeks. Nine patients refused or were not eligible for chemotherapy. Five patients received only one course and showed no response (NR); 9 patients received two courses; 18 patients received three or more courses. In the last group, complete remission (CR) was obtained in 9 cases, partial remission (PR) in 18 cases. The tumor markers studied did not show any significant difference in distinguishing LD from ED. NSE and TPS were significantly more often abnormal than TK, either at the time of diagnosis (p < 0.05) or in PR or NR patients (p < 0.05). In relation to chemotherapy response, NSE and TPS serum patterns were shown to be more reliable than TK in PR (p < 0.05) and NR patients (computed error between 10% and 15%). No significant difference was observed between serum NSE and TPS patterns. Serum NSE and TPS seem to be more useful in the diagnosis and follow-up of SCLC patients undergoing chemotherapy. Further trials are necessary to ascertain whether the associated assessment of NSE and TPS can add useful information to that provided by the assessment of NSE alone.

Aged↗
PubMed1989

[Serum level of neuron-specific enolase: value as tumor marker of microcellular bronchial cancer].

This study analyses retrospectively the plasma level of neuron-specific enolase (NSE) performed in 236 patients presenting for the diagnosis of a bronchopulmonary disease. Taking a cut off on 15 micrograms/L, 61 (64%) of the 95 patients sharing a small cell lung cancer (SCLC) (45% of those with a limited disease and 90% with an extensive disease) but 8 (13%) of 60 with a non small cell lung cancer patients and 0% of those with a benign bronchopulmonary disease showed an abnormal value of NSE. Therefore in this group of patients, the diagnosis of SCLC could be assessed with a sensitivity of 64% and a specificity of 94% in patients with an NSE plasma level above 15 micrograms/L. In addition, the interest of sequential dosages of NSE for the monitoring of SCLC patients is also stressed.

Biomarkers, Tumor↗
PubMed1996

Do neuron-specific enolase levels discriminate between small-cell lung cancer and mediastinal tumors?

The capacity of pretherapeutically assessed neuron-specific enolase (NSE) to differentiate between small cell lung cancer (SCLC) and mediastinal tumors was investigated retrospectively in a series of 320 patients. NSE was found to be increased in 95/130 (73.1%) patients with SCLC, in 4/62 (6.5%) patients with Hodgkin's disease, in 10/58 (17.2%) patients with non-Hodgkin's lymphoma, in 5/16 (31.3%) patients with teratoma, and in 6/54 (11.1%) patients with thymoma. The cut-off value, defined as the 95% percentile of a reference population suffering from benign pulmonary disorders (n = 192), was set at 13.8 ng/ml. When this discrimination level was increased to 26.4 ng/ml, which corresponds to a 95% specificity versus the total group with mediastinal tumors, SCLC was recognized with a detection rate of only 49.2%. In conclusion, increased NSE concentrations in a patient with a hilar mass and/or mediastinal widening on X-ray are not always diagnostic of SCLC due to the high rate of elevated NSE values associated with mediastinal tumors. However, in a patient who presents with a hilar mass and a high NSE level, bronchoscopy is always indicated to obtain adequate specimens for histology in order to plan an appropriate therapeutic regimen.

Adolescent↗
PubMed1997

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part I--The effects of heparin, protamine and propofol.

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) (Sangtec Medical, Sweden) assays are designed for clotted samples, but when studying cerebral damage following cardiac surgery, perioperative samples will contain heparin and/or protamine. The lipid emulsion propofol is also frequently used during cardiac surgery and could affect the assays. We, therefore, studied the effects of heparin, protamine and propofol on the accuracy of NSE and S-100 assays in five healthy patients. Blood samples were taken and divided into four groups: normal saline was added to group A; heparin to group B; heparin followed by protamine to group C; and propofol to group D. NSE and S-100 concentrations were measured for all samples. Neither heparin, protamine nor propofol affected the accuracy of S-100 and NSE assays; therefore, samples can be taken throughout operations involving cardiopulmonary bypass without influencing the results.

Anesthetics, Intravenous↗
PubMed1985

Serum neuron-specific enolase. A marker for disease extent and response to therapy for small-cell lung cancer.

Serum neuron-specific enolase (S-NSE) levels in 43 newly diagnosed untreated patients with small-cell lung cancer (SCLC) were compared with levels in 35 adult controls, 14 patients with non-small cell lung cancer (N-SCLC), and nine patients with noncancerous lung disease (N-CLD). The S-NSE level was raised (greater than or equal to 16 ng/ml) in 28 of 43 patients with SCLC, six of 16 patients with limited stage SCLC, and 22 of 27 of those with extensive stage SCLC. Extensive stage patients with SCLC had a significantly higher mean S-NSE level (50 ng/ml) than did limited stage patients with SCLC (16 ng/ml). Mean S-NSE levels in patients with N-SCLC and in patients with N-CLD were respectively 11 and 7 ng/ml. Serial measurements performed on 19 patients between the three-day-courses of chemotherapy showed an excellent correlation between S-NSE and clinical evolution. In addition, S-NSE was measured during the first three-day course of chemotherapy in 13 other patients; among them, seven had S-NSE levels greater than or equal to 100 ng/ml (mean: 490 ng/ml); these seven patients were responders; the remaining six had S-NSE levels less than 100 ng/ml (mean 28 ng/ml): among them, only two were responders. Such S-NSE measurements during the first cytostatic course seem to reflect the importance of tumor burden and may be valuable as early indicators of the response rate to chemotherapy.

Antineoplastic Agents↗
PubMed2004

S-100B and neuron specific enolase in outcome prediction of severe head injury.

OBJECTIVE: To elucidate the role of S-100B and neuron specific enolase (NSE) in predicting the outcomes of patients with severe head injury. METHODS: Forty patients with severe head injury were included in this study. The serum concentrations of S-100B and NSE were measured within 12 hours after head injury to investigate the correlation between serum levels of S-100B and NSE and outcome. Validity of both S-100B and NSE in outcome prediction was assessed with Receiver Operator Characteristic (ROC) curve. RESULTS: The serum concentrations of S-100B and NSE of both groups, with favorable or unfavorable outcomes, were significantly higher than those of the normal group. The serum concentrations within 12 hours after head injury were closely correlated with the prognosis. Furthermore, according to the ROC curves of S-100B and NSE, S-100B was found better in predicting outcomes than NSE. CONCLUSIONS: S-100B and NSE may play important roles in outcome prediction after severe head injury. Moreover, S-100B is clearly superior to NSE in terms of predictive value and appears to be a more promising serum marker in outcome prediction after severe head injury.

Craniocerebral Trauma↗
PubMed1991

Carcinoembryonic antigen, neuron-specific enolase and creatine kinase-BB as tumor markers for carcinoma of the lung.

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and creatine kinase-BB (CK-BB) were estimated in blood serum of 75 patients with primary lung carcinoma and of 20 patients with nonmalignant lung diseases. CEA and NSE were determined by immunoenzymatic method using monoclonal antibodies (Abbott CEA-EIA and Roche NSE-EIA) and CK-BB was assayed using kits supplied by Boehringer-Mannheim (Monotest CK-NAC aktiviert). Enhanced levels of CEA were observed in 64% of patients with lung carcinoma, mainly with adenocarcinoma. Increased activities of NSE and CK-BB were obtained in 47% and 39% of patients, respectively, principally of those with small cell carcinoma. The CEA level was dependent on the stage of advanced NSCLC carcinoma and of NSE and CK-BB on the stage of advanced SCLC carcinoma. The complex analysis of the three markers has given 100% specificity of test.

Adult↗
PubMed1985

Radioimmunoassay development for human neuron-specific enolase: with some clinical results in lung cancers and neuroblastoma.

A double-antibody radioimmunoassay for human neuron-specific enolase (NSE) was developed, using rabbit antiserum against the gamma subunit of enolase purified from human brain. Intra-assay variance was 3.8-5.1% and inter-assay variance 4.3-7.3%, and recovery of NSE added to normal serum was 100.2% on average. Normal serum NSE levels for 451 adults ranged from 3.6 to 10.8 ng/ml (mean 6.6 ng/ml). Antibodies raised against the gamma gamma enolase isozyme did not cross-react with the alpha alpha and beta beta isozymes at concentrations of 1,000 ng/ml, but showed a cross-reactivity of 41.5% (theoretically 50%) with the alpha gamma isozyme. It was also shown that hemolysis of 160 mg/dl hemoglobin can add 5.73 ng/ml of NSE to the true level. The coefficient of correlation between the radioimmunoassay and the sandwich enzyme immunoassay [1] was 0.99 (n = 21), and values determined by the RIA were about twice those obtained by the EIA. Serum NSE was abnormally high in 42 of 52 patients (80.8%) with small cell lung carcinoma, and in all 38 children with neuroblastoma.

Adolescent↗
PubMed1984

Neuron-specific enolase as a marker for neuroblastoma and small-cell carcinoma of the lung.

The use of neuron-specific enolase (NSE, E.C. 4.2.1.11) as a clinical marker for neuroblastoma and small-cell carcinoma of lung (SCCL) is presented. Both tumors have a high content of NSE as demonstrated enzymatically or by immunocytochemistry. Other retroperitoneal tumors in children and other lung tumors had insignificant NSE concentrations. NSE can thus be used in the differential diagnosis of neuroblastoma and SCCL. 73% of patients with SCCL had elevated serum NSE levels. The corresponding figure for patients with other types of lung cancer was 3%. There was a good correlation between serum NSE levels and the clinical course of patients with SCCL.

Adult↗
PubMed1998

[Clinical significance of serum neuron-specific enolase in non-small cell lung cancer].

The present study was a retrospective analysis of serum neuron-specific enolase (NSE) assayed in 302 patients with non-small cell lung cancer (NSCLC) before treatment. Serum NSE ranged from 0.6 to 183.0 ng/ml, with a mean value of 12.2 ng/ml, and exceeded 10 ng/ml in 145 patients (48.0%). The mean levels and rate of NSE positivity in 177 patients whose tumors were categorized as small, medium and large (from the product of the maximum and perpendicular axis of the tumor on chest X-ray), were highest in the large group. There was no significant relationship between serum NSE and the response rate to anticancer chemotherapy. The survival period of the patients with elevated serum NSE (median, 5.7 months) was significantly shorter, than those with normal serum NSE levels (median, 12.1 months). Serum NSE is of prognostic significance in a multivariate analysis (p < 0.01), but not predictive of response to chemotherapy in NSCLC.

Aged↗
PubMed1998

A novel neuron-specific aminopeptidase in rat brain synaptosomes. Its identification, purification, and characterization.

A specific aminopeptidase localized exclusively in neurons of the central nervous system was identified with an automated continuous-flow aminopeptidase analyzer developed recently in this laboratory. The enzyme was purified from rat brain 4933-fold to homogeneity with 9.3% recovery by ammonium sulfate fractionation, followed by column chromatography successively on phenyl-Sepharose, Sephadex G-200, and twice on Mono Q FPLC. The purified single-chain enzyme was estimated to be 110 kDa in molecular mass. It has a pI of 5.25 and a pH optimum of 7.0. Only Mg(II) restores the activity of the apoenzyme. The neutral aminopeptidase hydrolyzes beta-naphthylamides of amino acids with aliphatic, polar uncharged, positively charged, or aromatic side chains. It has a Km of 95 microM and a kcat of 7.8 s-1 on methionine-enkephalin, releasing only the N-terminal tyrosine. The thiol-dependent metallo-enzyme is most sensitive to amastatin inhibition with a Ki of 0.04 microM, and is the aminopeptidase most sensitive to puromycin. Its properties are different from those of the ubiquitous puromycin-sensitive aminopeptidase obtained from the same enzyme preparation. The blocked N terminus, substrate and inhibitor specificity, hydrolytic coefficiency, metal effects, pI, molecular weight, and catalytic site show that this enzyme is distinct from all other known aminopeptidases. Its enrichment in the synaptosomes suggests that this first reported neuron-specific peptidase plays a role in neurotransmission and synaptic differentiation.

Amino Acid Sequence↗
PubMed1992

NeuN, a neuronal specific nuclear protein in vertebrates.

A battery of monoclonal antibodies (mAbs) against brain cell nuclei has been generated by repeated immunizations. One of these, mAb A60, recognizes a vertebrate nervous system- and neuron-specific nuclear protein that we have named NeuN (Neuronal Nuclei). The expression of NeuN is observed in most neuronal cell types throughout the nervous system of adult mice. However, some major cell types appear devoid of immunoreactivity including cerebellar Purkinje cells, olfactory bulb mitral cells, and retinal photoreceptor cells. NeuN can also be detected in neurons in primary cerebellar cultures and in retinoic acid-stimulated P19 embryonal carcinoma cells. Immunohistochemically detectable NeuN protein first appears at developmental timepoints which correspond with the withdrawal of the neuron from the cell cycle and/or with the initiation of terminal differentiation of the neuron. NeuN is a soluble nuclear protein, appears as 3 bands (46-48 x 10(3) M(r)) on immunoblots, and binds to DNA in vitro. The mAb crossreacts immunohistochemically with nervous tissue from rats, chicks, humans, and salamanders. This mAb and the protein recognized by it serve as an excellent marker for neurons in the central and peripheral nervous systems in both the embryo and adult, and the protein may be important in the determination of neuronal phenotype.

Animals↗
PubMed2003

F2-isoprostane and neuron-specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children.

It has been hypothesized that oxidative stress plays an important role in mediating secondary damage after traumatic brain injury (TBI). To study the relationship between lipid peroxidation, clinical variables, and neuronal damage in pediatric TBI, we measured levels of F2-isoprostane, a marker of lipid peroxidation, and neuron-specific enolase (NSE), a marker of neuronal damage, in serial cerebrospinal fluid (CSF) samples from 23 infants and children with severe TBI (Glasgow Coma Scale score <8). These were compared to CSF samples from 10 uninjured pediatric controls. On d1 after injury, F2-isoprostane was increased 6-fold vs. control (36.59+/-8.96 pg/ml vs. 5.64+/-8.08 pg/ml, p=0.0035) and NSE was increased 10-fold (100.62+/-17.34 ng/ml vs. 8.63+/-2.76 ng/ml, p=0.0002). Multivariate analysis of F2-isoprostane levels and selected clinical variables showed a trend toward an inverse association with time after injury (p=0.0708). Multivariate analysis of NSE levels and selected variables showed a positive association between d1 NSE and F2-isoprostane (p=0.0426). CSF F2-isoprostane increases early after TBI in infants and children and is correlated with NSE, supporting a role for oxidative stress in the evolution of secondary damage early after severe TBI in infants and children.

Adolescent↗
PubMed1996

Conditionally immortalized neural progenitor cells grafted to the striatum exhibit site-specific neuronal differentiation and establish connections with the host globus pallidus.

The cell line RN33B has been reported to differentiate into neurons in a site-specific manner when grafted to the cortex and hippocampus of adult rats. To investigate the fate of RN33B cells in a subcortical structure, we grafted RN33B cells into the intact or excitoxically lesioned striatum of adult or neonatal rats. The total number and phenotypic characteristics of the [3H]thymidine-labeled grafted cells were analyzed at different time points after transplantation. Transplanted RN33B cells were found to survive, integrate, and differentiate into both neurons and astrocytes, and a significant proportion of the cells (approx. 10%) were found to differentiate into cells with morphological and phenotypic characteristics of medium-sized striatal projection neurons. Retrograde tracing showed that at least some of the graft-derived neurons were capable of establishing connections with one of the primary striatal targets, the globus pallidus. These findings demonstrate a remarkable capacity of the RN33B cells for site-specific neuronal differentiation in both the adult and the developing striatum and suggest that the same differentiating factors that are operating during normal neurogenesis in brain development are retained, at least to some extent, also in the adult CNS.

Adult↗
PubMed1984

Immunostaining of neuron-specific enolase is a valuable aid to the cytological diagnosis of neuroendocrine tumours of the lung.

The neuroendocrine marker neuron-specific enolase (NSE) has been reported to be detectable by immunohistochemistry in paraffin sections of neuroendocrine neoplasms of the lung. There is no study of immunodetection of NSE in cytological smear preparations from these tumours. We have examined 10 cases of small cell carcinoma of the lung, using cells obtained from serous fluids or bronchial biopsies, and found all but one had NSE-like immunoreactivity. No such immunoreactivity was found in 26 serous fluids and 19 biopsies from non-small-cell carcinomas. It is suggested, therefore, that immunostaining for NSE is a valuable aid to the cytological diagnosis of small cell carcinoma of the lung.

Ascitic Fluid↗
PubMed2003

Are serum S100beta proteins and neuron-specific enolase predictors of cerebral damage in cardiovascular surgery?

OBJECTIVE: To examine whether serum concentrations of S100beta protein and neuron-specific enolase (NSE) are predictors of cerebral damage in cardiovascular surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Eighteen patients with conventional cardiopulmonary bypass (CPB), 7 with selective cerebral perfusion (SCP), and 3 volunteers (blood samples). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: S100beta and NSE were measured in the blood obtained at 7 time points during and after operation. The concentrations of these markers in the blood from the surgical field and the cell-saver device, and the influence of graded hemolysis (in vitro) on the concentrations of these proteins were also examined. The mean values of S100beta in the CPB group (2.08 +/- 2.00 ng/mL) and the SCP group (1.46 +/-0.77 ng/mL) were highest after aortic declamping and after termination of SCP, respectively. The mean values of NSE in the CPB group (29.1 +/- 14.0 ng/mL) and the SCP group (31.2 +/- 13.6 ng/mL) were highest after termination of CPB and at the end of the operation, respectively. Three patients suffered from cerebral complications, but the elevation of these markers during operation was indistinguishable from those in the other patients. Peak concentrations of S100beta protein in the CPB group and NSE in the SCP group were correlated with the duration of aortic cross-clamping and CPB, respectively. S100beta protein and NSE concentrations in the blood from the surgical field were significantly larger than those in arterial blood, whereas the concentrations in the blood in the cell-saving device were not elevated. The concentration of S100beta protein was not influenced by the extent of hemolysis, whereas NSE concentration was markedly elevated by hemolysis. CONCLUSION: A large part of the increases in S100beta protein and NSE during CPB and SCP is not attributed to neuronal damage, but to contamination with the blood from the surgical field. To determine whether these markers are useful to predict neurologic complications, it will be necessary to exclude contamination from the surgical field as observed in the present study.

Aged↗
PubMed2003

[Expression of neuron-specific enolase and olfactory marker protein in the developing olfactory mucosa of human fetuses].

OBJECTIVE: To study the expression of neuron-specific enolase (NSE) and olfactory marker protein (OMP) in the developing olfactory mucosa of human fetuses. METHOD: The expression of NSE and OMP in the olfactory mucosa of 6 human fetuses (12, 16, 20, 24, 28 and 34 weeks) was studied using the technique of immunohistochemistry. RESULTS: NSE immunological positive reactions were seen in all 6 fetal mucosa from gestational 12 (G12) to G34, with plenty of positive-stained dual-pole neuron cells. At G12, the positive cells aligned tightly, the cell bodies were localized in the lower portion of olfactory epithelium and the positive-stained area occupied upper 2/3 of fetal nasal mucosa. With the development, the positive cells gradually became multilayer, but the density and the relative area of positive-cells reduced. At G34, the positive cells were located only in upper 1/3 of nasal mucosa. OMP-positive reactions were localized in a few dual-pole neurons at G12, the number was much less than NSE-positive cells in the same fetus. With the development, the OMP-positive cells gradually increased with most of the cell bodies located in the upper portion of epithelium, but number still relatively less than the NSE-positive cells at the same age. CONCLUSION: At G12, there were lots of olfactory neuron in the olfactory mucosa and only a few olfactory neurons had became mature. With the development, the olfactory epithelial area reduced but the number of mature olfactory neurons increased. At the last trimester, fetal olfactory sensor was almost matured.

Female↗
PubMed2002

Clinical significance of serum neuron-specific enolase in patients with adult T-cell leukemia.

The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with adult T cell-leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type-1 (HTLV-1). Serum NSE values >10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV-1 carriers. Contrary to previous findings demonstrating that 20% of patients with non-Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin-2 receptor (sIL-2R) levels (P < 0.04 and P < 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log-rank test (P < 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL.

Aged↗