Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor markers are developmentally regulated proteins or carbohydrate molecules, which are expressed in specific tissues in the fetus during certain developmental periods. With malignant transformation, these molecules are reexpressed in neoplastic tissues. Some developmental or metabolic disorders can also lead to the expression of tumor marker genes, hereditary tyrosinaemia and ataxia teleangiectasia associating with elevated serum alpha-fetoprotein are examples of such conditions. In pediatric malignancies, the most common markers in clinical use are alpha-fetoprotein in liver and yolk sac tumors, chorionic gonadotropin in germ cell tumors, and catecholamines and neuron specific enolase in neuroblastoma. Several other molecules including carbohydrate antigens CA 19-9 and CA 125 may also have a role in the diagnosis and follow-up of distinct types of childhood malignancies. The non-specificity of several markers, such as tissue polypeptide antigen and sialic acid, greatly hampers their clinical use. In this review we will discuss the biology and current knowledge on the use of serum and urine tumor markers. We also highlight the putative future use of these molecules in cancer diagnosis and therapy, including the use of monoclonal antibodies directed against these antigens.
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PMID:Clinical use of tumor markers in childhood malignancies. 1245 76

Adrenal incidentalomas are a heterogeneous group of pathological entities, including benign or malignant adrenocortical or medullary tumors, hormonally active or inactive lesions, which are identified incidentally during the examination of nonadrenal-related abdominal complaints. About 1.5% to 23% of adrenal incidentalomas are pheochromocytomas. Composite pheochromocytoma is a rare tumour of adrenal medulla with divergente clinical course. This type of pheochromocytoma is designated "composite" or "mixed," depending on whether pheochromocytoma and nonpheochromocytoma components show the same embryologic origin. Nonpheochromocytoma components found in the composite pheochromocytoma include ganglioneuroma, ganglioneuroblastoma, neuroblastoma, and malignant schwannoma. The biologic behavior of composite pheochromocytomas may be as difficult to predict as more traditional pheochromocytomas; based on the number of cases reported to date the presence of areas resembling ganglioneuroblastoma or neuroblastoma does not necessary indicate a poor prognosis. Some may behave in a malignant fashion with metastasis by a component of the tumour which has neural features. Pheochromocytomas and paragangliomas are well-defined entities. Some of their nonsporadic associations and unusual morphological appearances are not universally appreciated. We report on a rare association of left adrenal CP, with typical right adrenal phochromocytoma and retroperitoneal paraganglioma, and a review of literature. We analyzed the clinical and immunohistochemical features in a 24-year-old woman with composite pheochromocytoma localized in the left adrenal gland and associated with blood pressure of 200/140 mmHg. Abdominal computed tomography and 131-J MIBG revealed a 65 x 60 mm mass in the right adrenal gland, but no revealed 45 x 40 mm retroperitoneal mass and 20 x 20 mm mass in the left adrenal region. Serum and urinary adrenaline levels were high, and catecholamine levels in the blood sample of the selective adrenal vein, were also high. Bilateral adrenalectomy and retroperitoneal mass were surgically removed without complications. Clinical symptoms were absent 6 years after surgery. After surgery the patient gave birth to two healthy babies. Immunohistochemical analyses revealed that tumour cells of right adrenal pheochromocytoma and retroperitoneal paraganglioma were strongly positive for neurone specific enolase, synaptophisin and chromogranin A. The left adrenal tumour showed pheochromocytoma, ganglioneuroma and neuroblastoma components. Immunoreactivity of this tumour added several features to the wide immunohistochemical spectrum. This case demonstrates the indolent behavior of sporadic-type CP and retroperitoneal paraganglioma in an adult patient. Unusual morphological features of CP occur in a substantial number of cases and may cause diagnostic problems.
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PMID:[Pheochromocytomas as adrenal gland incidentalomas]. 1258 98

The authors described three cases of intraabdominal desmoplastic small round cell tumour of the peritoneum (IDSRT). In one case the patient was a woman, and in the other two men. The age ranged from 20-29 years. Common of all the cases was a rapid onset of clinical symptoms during the period of twelve to eighteen months. In one case, a 22-year-old woman presented with a symptomless course of disease documented by medical examination one month ago. Intensive chemotherapy was applied but two patients died of generalisation. The 22-year-old woman is alive but with clinical evidence of generalisation in the abdominal cavity. The "classical" type of IDSRT was found in all the cases. Sharply demarcated groups of tumour cells of different size were surrounded by dense fibrous stroma. In some regions desmoplastic areas prevailed. In one case the tumour consisted of round and oval cells resembling a lymphoma. In the other two cases, the slightly elongated cells were present. Immunohistologically, the small round cells were positive for cytokeratins with antibody AE1-AE3. Membrane and dot-like paranuclear positivity were found. In 2 cases the reaction to desmin was seen in a dot-like paranuclear distribution, whereas the reaction to smooth muscle actin (MSA) was negative. In all the cases positivity to vimentin and neuron specific enolase (NSE) were apparent. Negative reactions were found for WT-1 antibody in all three cases. In one of the cases the RT PCR reaction for chimeric gene EWS/WT1 was performed, and found to be negative. Many different tumour types, such as lymphoma, Ewing sarcoma/PNET, neuroblastoma, alveolar rhabdomyosarcoma, malignant mesothelioma must be excluded. Cytogenetic examination should be performed on tumours with a "non-typical" histological pattern and uncommon immunohistological examinations.
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PMID:[Intra-abdominal desmoplastic small-cell tumor of the peritoneum]. 1287 4

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.
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PMID:MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening. 1667 Jul 17

A proteomic approach was used to identify 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) protein targets in human neuroblastoma SH-SY5Y cells. By using biotinylated 15d-PGJ2, beta-actin was found as the major adducted protein; at least 12 proteins were also identified as minor biotin-positive spots, falling in different functional classes, including glycolytic enzymes (enolase and lactate dehydrogenase), redox enzymes (biliverdin reductase), and a eukaryotic regulatory protein (14-3-3gamma). 15d-PGJ2 induced marked morphological changes in the actin filament network and in particular promoted F-actin depolymerization as confirmed by Western blot analysis. By using a mass spectrometric approach, we found that 15d-PGJ2 reacts with isolated G-actin in a 1:1 stoichiometric ratio and selectively binds the Cys374 site through a Michael adduction mechanism. Computational studies showed that the covalent binding of 15d-PGJ2 induces a significant unfolding of actin structure and in particular that 15d-PGJ2 distorts the actin subdomains 2 and 4, which define the nucleotide binding sites impeding the nucleotide exchange. The functional effect of 15d-PGJ2 on G-actin was studied by polymerization measurement: in the presence of 15d-PGJ2, a lower amount of F-actin forms, as followed by the increase in pyrenyl-actin fluorescence intensity, as the major effect of increasing 15d-PGJ2 concentrations occurs on the maximum extent of actin polymerization, whereas it is negligible on the initial rate of reaction. In summary, the results here reported give an insight into the role of 15d-PGJ2 as a cytotoxic compound in neuronal cell dysfunction. Actin is the main protein cellular target of 15d-PGJ2, which specifically binds through a Michael adduction to Cys374, leading to a protein conformational change that can explain the disruption of the actin cytoskeleton, F-actin depolymerization, and impairment of G-actin polymerization.
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PMID:Identification of actin as a 15-deoxy-Delta12,14-prostaglandin J2 target in neuroblastoma cells: mass spectrometric, computational, and functional approaches to investigate the effect on cytoskeletal derangement. 1729 18

The aim of the study was to isolate and characterize a population of neuronal progenitors in the human umbilical cord blood (HUCB) mononuclear cell (MNC) fraction, for in vitro manipulation towards neuronal differentiation. Selection of the HUCB neuronal progenitors (HUCBNPs) was based on the neuronal prerequisite for adherence to collagen. Populations of collagen-adherent, nestin-positive (94.8+/-2.9%) progenitors expressing alpha1/2 integrin receptors, as revealed by Western blot and adhesion assay using selective antagonists, were isolated and survived for more than 14 days. In vitro differentiation of the HUCBNPs was achieved by treatment with 10% human SH-SY5Y neuroblastoma cell-conditioning media (CM) supplemented with 10 ng/ml nerve growth factor (NGF). Some 83+/-8.2% of the surviving progenitors acquired a neuronal-like morphology, expressed by cellular outgrowths of different lengths. About 35+/-6% of the HUCBNPs had long outgrowths with a length/cell diameter ratio greater than 2, typical of developing neurons. The majority of these progenitors, analyzed by immunocytochemistry and/or RT-PCR, expressed common neuronal markers such as microtubule-associated protein 2 (MAP-2; 98.5+/-2%), neurotrophin receptor (TrkA; 98.5+/-0.06%), neurofillament-160 (NF-160; 94.2+/-1%), beta-tubulin III (89.8+/-4.2%) and neuron specific enolase (NSE). Combined CM and NGF treatment induced constitutive activation of the mitogen-activated protein kinases ERK2 (36-fold vs control), p38alpha (nine-fold vs control) and p38beta (23-fold vs control), most likely related to survival and/or differentiation. The results point to operationally defined conditions for activating neuronal differentiation of HUCBNPs ex vivo and emphasize the crucial role of neuronal CM and NGF in this process.
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PMID:Neuronal conditioning medium and nerve growth factor induce neuronal differentiation of collagen-adherent progenitors derived from human umbilical cord blood. 1787 63

Anaplastic large cell neuroblastomas (ALCNB) are a subset of undifferentiated neuroblastomas with marked pleomorphic and anaplastic features that render them diagnostically challenging. We reviewed the records of all patients diagnosed with ALCNB at Children's Healthcare of Atlanta (Egleston Children's Hospital) for their clinical, biologic, and pathologic characteristics and their treatment outcomes. From 1998 to 2006, 7 patients were diagnosed with ALCNB. All patients presented with abdominal-pelvic masses, 3 of them of adrenal origin and 2 with thoracic extension, with clinical stages 3 or 4, and were considered to have high-risk disease. The N-MYC oncogene was amplified in 3 cases and catecholamines were elevated in 5 of 6 patients tested. All pretreatment tumors demonstrate pleomorphic, anaplastic morphology with bizarre mitoses admixed with undifferentiated but monomorphic cells with minimal if any neuropil or neuro-ganglionic differentiation. Immunohistochemical markers for neuron specific enolase (NSE) and synaptophysin were strongly positive in all specimens and chromogranin in 4 of 5. Interestingly, all tumors showed strong Fli-1 nuclear positivity despite a negative CD-99 stain. However, reverse transcription polymerase chain reaction or fluorescent in-situ hybridization testing for Ewing sarcoma transcripts was negative in 4 available specimens. This same Fli-1 antibody had tested negative on 30 conventional neuroblastomas, indicating a peculiar cross reactivity with this subset of ALCNB. Posttreatment biopsies showed maturation changes to more conventional neuroblastoma histology in 5 of the 7 cases. Follow-up ranged from 9 months to 4 years from diagnosis (median: 25 months). Five patients are still alive after treatment, 1 died 9 months after diagnosis, and another patient refused high-risk therapy and progressed and died 9 months from diagnosis. Anaplastic large cell neuroblastomas are a subset of undifferentiated neuroblastomas characterized by the absence or marked paucity of histologic clues for the diagnosis of neuroblastoma. Although all these tumors are strongly positive for NSE and synaptophysin, they also show Fli-1 positivity. However, they are negative by molecular testing for EWS transcripts, and they are immunohistochemically negative for CD99. The true neuroblastic nature of these tumors is supported by the N-MYC oncogene amplification in some of them, catecholamine production, immunohistological reactivity, and their posttherapy maturation to a more recognizable neuroblastic morphology. Although follow-up is still somewhat limited, the response and survival of the patients in our institution is better than a previous European study that indicated an aggressive clinical behavior of these tumors, although treatment modalities were not described in that report. Further study of this variant of neuroblastoma with more patients is required to determine optimal therapy, more accurately predict outcome, and to ascertain if ALCNB are a distinct biologic group of neuroblastomas.
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PMID:Anaplastic large cell neuroblastoma. 1839 55

Neuroblastoma is the most common childhood cancer, which arises from sympathetic neural precursors. Because the prognosis of advanced neuroblastoma is known to be poor, developments of new anti-cancer drugs are desperately needed. For screening of therapeutic drugs for neuroblastoma, genetically engineered animal models would be useful. In an attempt to obtain transgenic mice carrying simian virus 40 T-antigen gene under control of tetracycline responsive elements with cytomegalovirus promoter, we found one line of mice exhibiting bilateral adrenal tumors by leakage expression of T-antigen in adrenal gland. These adrenal tumors contained small round tumor cells with increased N/C ratio, showing chromogranin A and neuron specific enolase-like immunoreactivity. By electron microscopy, tumor cells containing neuritic processes with synaptic vesicles surrounding them were observed. The plasma levels of dopamine were significantly elevated in these transgenic mice. MYCN expression levels were significantly elevated in these tumors. These findings indicated that the adrenal tumor was a neuroblastoma. This mouse model would be a useful tool for development of chemotherapeutic drugs and understanding the etiology of neuroblastoma.
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PMID:Establishment of a novel neuroblastoma mouse model. 1902 Jul 52

Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all-trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP+, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore, undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research.
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PMID:Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. 1989 43

Neurons of enteric nervous system (ENS) regulate intestinal epithelial cells (IEC) functions but whether IEC can impact upon the neurochemical coding and survival of enteric neurons remain unknown. Neuro-epithelial interactions were studied using a coculture model composed of IEC lines and primary culture of rat ENS or human neuroblastoma cells (SH-SY5Y). Neurochemical coding of enteric neurons was analysed by immunohistochemistry and quantitative PCR. Neuroprotective effects of IEC were tested by measuring neuron specific enolase (NSE) release or cell permeability to 7-amino-actinomycin D (7-AAD). Following coculture with IEC, the percentage of VIP-immunoreactive (IR) neurons but not NOS-IR and VIP mRNA expression were significantly increased. IEC significantly reduced dopamine-induced NSE release and 7-AAD permeability in culture of ENS and SH-SY5Y, respectively. Finally, we showed that NGF had neuroprotective effects but reduced VIP expression in enteric neurons. In conclusion, our study identified a novel role for IEC in the regulation of enteric neuronal properties.
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PMID:Neuroplasticity and neuroprotection in enteric neurons: role of epithelial cells. 1930 81


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