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)

Neuroblastoma is the second most common solid tumor in children. The prognosis is poor for approximately 70% of patients who have widespread disease at the time of diagnosis. The use of new strategies for classification and therapy has raised expectations for cure in advanced neuroblastoma. We summarise results and experiences reached during the last decade.
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PMID:[Advances in the diagnosis and treatment of neuroblastoma]. 965 Mar 46

Direct experimental evidence shows that tumor growth and metastases are angiogenesis-dependent. Neuroblastoma (NB) is the most common extracranial malignant solid tumor of childhood. In this study, we investigated 2 human NB cell lines, LAN-5 and GI-LI-N, for their capacity to secrete 2 extracellular matrix-degrading enzymes, MMP-2 and MMP-9, and to induce in vitro human microvascular endothelial cells (EC) to proliferate and in vivo angiogenesis in the chick embryo chorio-allantoic membrane (CAM) assay. Conditioned medium (CM) from both cell lines stimulated in vitro EC proliferation and the effect of LAN-5 CM was higher than that of GI-LI-N cells. Moreover, anti-VEGF, but not anti-FGF2 antibodies, prevented growth increment of EC. NB cell lines secreted the active form of MMP-2 almost exclusively, LAN-5 cells more than GI-LI-N cells. Both cell lines, LAN-5 cells more than GI-LI-N ones, induced angiogenesis in the CAM assay. Our data suggest that the 2 NB cell lines are angiogenic, to LAN-5 cells more than GI-LI-N ones. LAN-5 cells are indeed endowed with a more aggressive and invasive phenotype.
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PMID:Human neuroblastoma cells produce extracellular matrix-degrading enzymes, induce endothelial cell proliferation and are angiogenic in vivo. 966 9

Neuroblastoma is the most common extracranial solid tumor in pediatrics. The long-term survival of patients with advanced-stage neuroblastoma has remarkably improved secondary to aggressive treatment protocols including autologous bone marrow transplant (BMT). As a result, a different natural history of this disease is being reported with unusual, late manifestations. The central nervous system (CNS), once a rare site of disease, is being involved with increasing frequency. Appropriate neuroimaging in these patients is important. Two cases of patients with treated stage IV neuroblastoma who developed isolated CNS metastases are presented. The proposed pathogenesis and neuroradiologic manifestations of this complication are reviewed.
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PMID:Central nervous system relapse of treated stage IV neuroblastoma. 988 Jun 49

Proteases of the plasminogen-plasminogen activator (PA) system play an important role in cancer metastasis. We have examined the expression of these proteases and their cell surface receptors and inhibitors in neuroblastoma, a tumor that originates in cells of the neural crest and is the second most common solid tumor in children. This analysis was performed in seven established human cell lines and 20 primary tumor specimens. Urokinase PA and, in particular, tissue-type PA were expressed in cell lines and in tumor tissues; however, their levels of expression did not correlate with clinical stage. There was little evidence suggesting that neuroblastoma cells concentrate PA activity at their cell surface because urokinase-type PA receptor mRNA was detected in two cell lines and in 5 of 20 tumor samples by reverse transcription-PCR only. PA inhibitor (PAI)-2 was absent in all cell lines and tumor tissue samples examined. However, PAI-1, which was not expressed by the cell lines, was expressed by stromal cells and, specifically, endothelial cells in tumor tissue. By extending the analysis of PAI-1 expression in 64 primary tumor specimens, we found that high PAI-1 expression paradoxically correlated with metastatic stage and tumor recurrence. In vitro experiments indicated that the expression of PAI-1 by human microvascular endothelial cells was stimulated in the presence of SK-N-BE(2) human neuroblastoma cells and neuroblastoma culture medium. Recombinant PAI-1 also promoted SK-N-BE(2) cell detachment from vitronectin and migration from vitronectin toward fibronectin. From these data, we conclude that the up-regulation of PAI-1 expression in endothelial cells may promote rather than inhibit metastasis in neuroblastoma.
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PMID:The plasminogen-plasminogen activator (PA) system in neuroblastoma: role of PA inhibitor-1 in metastasis. 1009 67

Neuroblastoma is the second most common malignant solid tumor in the pediatric population. Recent advances in treatment options and identification of prognostic subsets have made early detection important. Early classification into a favorable stage and subset may carry a 10-year survival of about 90% (1). With newer treatment regimens, the probability of long-term survival in patients with metastatic disease has also increased about fourfold since 1979 (2). Emergency physicians can contribute to improved morbidity and mortality with appropriate evaluation and disposition of the patient presenting with neuroblastoma. Two patients, a 6-month-old and a 2-week-old, presented to the Emergency Department with weakness. Both had a presumptive diagnosis of neuroblastoma made by the emergency physician. A brief discussion of the incidence, presentation, and diagnosis of neuroblastoma follows.
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PMID:Two cases of neuroblastoma presenting to the emergency department. 1019 84

Neuroblastoma is the most frequent solid tumor in childhood. We have analysed 48 neuroblastomas of different stages and degrees of cellular differentiation for CDK4 amplification by a fluorescent differential PCR assay. We explored the relative densitometric measure of a 119 bp fragment of the CDK4 gene versus an 82 bp fragment of the IFNG gene. We were not able to detect any case of CDK4 gene amplification in the neuroblastomas. In conclusion, CDK4 activation does not seem to be relevant to the development of neuroblastomas, at least through gene amplification.
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PMID:Lack of gene amplification as a mechanism of CDK4 activation in human neuroblastoma. 1020 8

Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal muscle lineage. With approximately 250 cases diagnosed yearly in the United States, it is the third most common extracranial solid tumor of childhood after Wilms' tumor and neuroblastoma. Important epidemiologic, biologic, and therapeutic differences have been elucidated within the RMS family. Common sites of primary disease include the head and neck region, genitourinary tract, and extremities. A site-based tumor-nodes-metastasis staging system is being incorporated into use for assessing prognosis and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system. The development of intensive multimodality treatment protocols tested in large-scale international trials has resulted in significant improvements in outcome, especially for patients with local or locally extensive disease for whom a 60%-70% disease-free survival can be expected. Despite aggressive approaches incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy, the outcome for patients with metastatic disease remains poor. Future challenges include the development of less toxic therapy for patients with localized disease and new approaches for patients with metastatic disease.
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PMID:Rhabdomyosarcoma: an overview. 1033 69

Neuroblastoma is a malignant solid tumor of childhood with a poor prognosis. The growth of solid tumors has been shown to be dependent on new blood vessel formation, i.e. angiogenesis. Several steps in the metastatic process have also been found to be angiogenesis-dependent. Neuroblastomas grow quickly, are highly vascularized, and metastasize early, and hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this disease. In order to investigate the effects of angiostatic agents in this disease, a new animal experimental model for human neuroblastoma was developed. Three angiostatic agents were tested in the model: TNP-470, the synthetic analogue of fumagillin, given subcutaneously, and the endogenous steroid 2-methoxyestradiol and its derivative 2-propynylestradiol, given orally. TNP-470 administration resulted in a significant reduction of the tumor growth rate and microvascular counts, and of the fraction of viable tumor cells, compared to controls. The fraction of apoptotic tumor cells increased threefold, while that of proliferative cells remained unaltered. This can explain the reduced net growth. Treatment with the angiostatic and chemotherapeutic steroids 2-methoxyestradiol and 2-propynylestradiol yielded similar results. However, the mechanism of action of these steroids was bimodal; the effect occurring both through inhibition of tumor angiogenesis and through induction of tumor cell apoptosis. It was shown for the first time that inhibition of angiogenesis regardless of agent induces striking chromaffin differentiation, observed as increased expression of insulin-like growth factor II gene, tyrosine hydroxylase, and chromogranin A, and increased formation of cellular processes. It is suggested that inhibition of angiogenesis induces metabolic stress, resulting in chromaffin differentiation and apoptosis. Such agonal differentiation may be the link between angiostatic therapy and tumor cell apoptosis. Angiostatic agents administered as single therapy have an objective tumoristatic effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a new and promising treatment modality that merits clinical investigation.
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PMID:Angiostatic treatment of neuroblastoma. 1037 67

Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine 5 were synthesized by diazotization of substituted 2-(2-aminophenyl)indoles followed by an intramolecular coupling reaction of the diazonium group with the indole nitrogen. To obtain the indolobenzotriazine system it was necessary to protect the 3 position of the indole nucleus to avoid cyclization into the indolo[3,2-c]cinnoline system 4. Indolobenzotriazines 5a-g were evaluated in vitro for antitumor activity against a panel of leukemia-, lymphoma-, carcinoma-, and neuroblastoma-derived cell lines. Some compounds inhibited the proliferation of T and B cell lines at submicromolar concentrations, whereas their activity against solid tumor cell lines was in the micromolar range. When evaluated for their antifungal potential 5a,d inhibited some of the fungi tested, although at concentrations very close to those inhibiting the proliferation of human cells. On the contrary, all indolobenzotriazines proved fairly potent and selective inhibitors of Streptococcus and Staphylococcus. In particular 5b,c,g were up to 80 times more potent than the reference drug streptomycin and inhibited the growth of the above Gram-positive bacteria at concentrations far lower than those cytotoxic for animal cells.
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PMID:Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine with potent antitumor and antimicrobial activity. 1041 76

Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia, even in all-trans retinoic acid-refractory cases, with minimal toxicity at low (1-2 microM) concentration. We exposed various neuroblastoma cell lines to As2O3 at a concentration of 2 microM: as a result, seven of 10 neuroblastoma cell lines underwent apoptosis characterized by morphological changes and nucleosomal DNA fragmentation. As2O3-induced apoptosis in neuroblastoma cells was shown to occur through the activation of caspase 3, as judged from Western blot analysis and apoptosis inhibition assay. It seemed that the sensitivity of neuroblastoma cells to As2O3 was inversely proportional to their intracellular level of reduced glutathione. Taken together these results indicate that As2O3 would be a candidate as a therapeutic agent for treatment of neuroblastoma, which is a solid tumor, not only by systemic therapy but also by local therapy.
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PMID:Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro. 1042 72


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