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)

Since 1947, we have treated 19 children with neuroblastoma whose first symptoms were paralysis or weakness of an extremity, and/or incontinence due to tumor in the spinal canal. In 18 patients, the spine tumor was part of a dumbbell tumor which was present in the adjacent paravertebral area and in one, no extraspinal tumor was found. Aggressive treatment was employed for all. In 17 children, the intraspinal tumor was treated by laminectomy and irradiation with and without chemotherapy. Radiation and chemotherapy were used for two. The extraspinal tumor was excised totally in six and partially in six. All 12 children received postoperative radiation and chemotherapy. In 6 children, the extraspinal tumor was treated only with radiation and chemotherapy. Nine of 19 children are alive without evidence of neuroblastoma. Thirteen patients showed either partial (6) or full (7) neurologic recovery. Survival was related to the child's age at diagnosis and the extent of disease. While 8 of 9 children under 1 yr of age survived, only 1 of 10 children over 1 yr survived. None of the 5 children with Stage IV disease at diagnosis could be saved. The degree and frequency of neurologic recovery were greatest in children whose neurologic symptoms had been present the shortest times and were equal among those who survived and those who died. The outlook for children who became paralyzed by neuroblastoma is not hopeless; therapy aimed at saving life or neurologic function is both worthwhile and rewarding.
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PMID:Prognosis for children with neuroblastoma presenting with paralysis. 87 30

Histocompatible bone marrow transplantation (BMT) is the treatment of choice for pediatric patients with second remission acute lymphoblastic leukemia or acute myelogenous leukemia (AML) and has been successfully used to treat patients with first remission AML and stable-phase chronic myelogenous leukemia. The principle causes of transplantation failure are recurrent leukemia and therapeutic toxicities, including idiopathic interstitial pneumonitis and graft versus host disease (GVHD). The likelihood of leukemic relapse is related primarily to the remission status of the patient; patients in first remission have a lower relapse rate than patients in second remission, and the relapse rate of both is less than that of patients in relapse. Interstitial pneumonitis is due, in part, to the total body irradiation (TBI) that is used to cytoreduce the patients. TBI administration has been modified to reduce its toxicity. Acute and chronic GVHD are due to the immuno-aggression of donor T-lymphocytes against recipient non-HLA antigens. The in vitro removal of the T-lymphocytes from the donor bone marrow inoculum reduces the incidence of acute and chronic GVHD but may have the adverse effect of reducing hematopoietic engraftment and increasing leukemic relapse since the graft versus leukemia effect may be eliminated. The expanding role of BMT includes its use in the treatment of nonleukemic neoplasms (neuroblastoma, solid tumors) and the use of histoincompatible BMT for eligible patients without histocompatible donors.
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PMID:Current status of bone marrow transplantation in pediatric oncology. 352 38

A 49-year-old woman had a 12-year history of a localized left orbital tumor that required five subtotal excisions, orbital radiotherapy, and finally an exenteration. The last procedure was performed after visual function had deteriorated and in order to prevent spread of the tumor into a surrounding compartment. The biopsy specimens from the first four surgeries showed a stroma-free spindle cell tumor with benign cytologic features and no mitotic activity, which exhibited palisading of nuclei, imbrication of delicate cytoplasmic processes (neuropil), true perivascular rosettes with cytoplasmic processes oriented perpendicular to vessel walls, and Wright rosettes. The biopsy after radiotherapy and the exenteration specimen contained more polyhedral (gemistocytoid) tumor cells with abundant eosinophilic cytoplasm and tapering cell processes; nuclear pleomorphism without mitotic activity was also seen. Electron microscopy showed the presence of neurosecretory dense-core granules in the perikaryon region of the tumor cells and in the myriad interweaving cytoplasmic processes (neurites); neither Nissl substance nor synapses were identified. Immunohistochemical staining for neuron-specific enolase was positive, but glial fibrillary acidic protein stained negative. This previously undescribed orbital tumor is interpreted as a primary differentiated neuroblastoma without evidence of ganglion cell differentiation that exhibited locally aggressive behavior. The distinctions between neuroblastic and neuroendocrine tumors are discussed.
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PMID:Primary differentiated neuroblastoma of the orbit. 358 3

We have analyzed DNA from 46 neuroblastoma tumors of all clinical stages and five ganglioneuroma tumors together with corresponding control DNA for loss of heterozygosity (LOH) on the distal 1p chromosomal region (1p-LOH). The markers used for the analyses were genetically mapped DNA polymorphisms detectable with PCR analysis. In general, there was concordance among aggressive tumor stage, 1p deletion, and N-myc amplification, although exceptions were found. Twelve (26%) of the 46 neuroblastoma tumors displayed 1p-LOH, 11 being stage 4 and 1 stage 2 (which progressed subsequently to stage 4), whereas 10 stage 4 tumors showed no 1p-LOH. Of 12 neuroblastomas shown to have N-myc amplification, 10 had 1p-LOH. In 8 cases it was possible to test for parental origin of the chromosome involved in 1p-LOH. No significant correlation between LOH and paternal or maternal allele was found. Commonly deleted loci in the distal 1p region in the neuroblastoma tumors indicated that the region for a tentative neuroblastoma tumor suppressor gene is defined proximally by marker D1S244 and distally by marker D1S80. One striking feature of three stage 2 neuroblastomas and one of the stage 3 tumors was the presence in the tumor DNA of alleles not present in the constitutional DNA of the patients, i.e., microsatellite instability. The significance of this phenomenon in localized neuroblastoma tumors remains to be clarified. Aggressive neuroblastoma in young children (younger than 2 years of age) seems to be a homogenous disorder consistently showing concomitant 1p-LOH and N-myc amplification. In the majority of unfavorable neuroblastoma in older children, however, neither 1p-LOH nor N-myc amplification could be detected. This indicates that neuroblastoma in older children is a biologically more heterogenous disorder in which genetic alterations other than deletions of chromosome 1p and amplification of N-myc also may contribute to tumorigenesis.
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PMID:Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas analyzed with short-tandem repeat polymorphisms. 758 54

Cartilage and bone-forming tumors of the mediastinum are extremely rare neoplasms with very few cases having been reported in the literature. We studied six cases of primary malignant cartilaginous tumors presenting as extraskeletal soft tissue masses in the posterior mediastinum. The patients were five women and one man aged 11 to 63 years (median, 31 years). Histologically, the lesions showed a spectrum of features that ranged from mesenchymal chondrosarcoma, to extraskeletal myxoid chondrosarcoma, to moderately well to poorly differentiated chondrosarcoma. In all cases, the lesions presented as well-circumscribed tumor masses centered in the soft tissues in the posterior mediastinum without radiographic evidence of origin from bone. Because of their relatively small size, good circumscription, focal areas of calcification, and posterior mediastinal location, the preoperative clinical diagnoses included benign neurogenic tumor and neuroblastoma. All of the lesions were treated by complete surgical excision, followed in two cases by postoperative radiation therapy. Clinical follow-up was available in five cases: two patients with mesenchymal chondrosarcoma presented with local recurrence after 3 and 7 years, one developed metastases to the sacrum 8 years after initial diagnosis and died, and one was alive and well without evidence of disease after 6 years. The patient with myxoid chondrosarcoma of the posterior mediastinum developed bilateral pulmonary metastases 10 months after surgery and has been lost to follow-up since. Our findings reinforce previous observations on the occurrence of extraskeletal cartilaginous tumors in the mediastinum and indicate that these tumors can show a propensity for local aggressive behavior with high recurrence rate and a definite potential for distant metastases. Such tumors should be considered in the differential diagnosis of malignant neoplasms presenting as a soft tissue mass in the posterior mediastinum.
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PMID:Malignant cartilaginous tumors of the mediastinum: clinicopathological study of six cases presenting as extraskeletal soft tissue masses. 915 7

The sinonasal undifferentiated carcinoma (SNUC) is an aggressive and rare neoplasm arising in the nasal cavity and the paranasal sinuses. To date, over 50 cases of histologically proven SNUCs have been reported since its original description in 1986. Presenting symptoms include facial pain, nasal obstruction, diplopia, epistaxis, proptosis, and periorbital swelling. The histologic features of this neoplasm include cohesive cells arranged in nests, ribbons, and trabeculae. The cells exhibit hyperchromatic nuclei and a high nuclear to cytoplasmic ratio. A brisk mitotic rate, tumor necrosis, and vascular invasion are prominent features. Confirming the diagnosis of SNUC at the light microscopic level can be challenging, since the microscopic differential diagnosis includes olfactory neuroblastoma, rhabdomyosarcoma, undifferentiated nasopharyngeal carcinoma (lymphoepithelioma), malignant lymphoma, malignant melanoma, and neuroendocrine (small cell undifferentiated; oat cell) carcinoma. Sinonasal undifferentiated carcinoma can be differentiated from these other neoplasms by correlating clinical, light microscopic, histochemical, immunohistochemical, and ultrastructural characteristics. Aggressive, multimodal therapy can provide the best opportunity for local control of this neoplastic process, but the optimal treatment has yet to be determined.
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PMID:Sinonasal undifferentiated carcinoma: a distinctive clinicopathologic entity. 1056 93

Neuroblastoma is the most common extracranial solid tumor of early childhood. This tumor demonstrates significant heterogeneity with respect to pathologic, genetic, and clinical features. The outcome varies from spontaneous regression or maturation to rapid progression, despite aggressive therapy. Prognostic factors have been found that identify those tumors which have a high probability of aggressive behavior; these factors include unfavorable histology, MYCN copy number, deletions of the short arm of chromosome 1, DNA content, and TRK-A (high-affinity receptor protein for nerve growth factor) expression. Recent studies have suggested that high levels of telomerase activity also correlate with poor clinical outcome. We investigated this relationship in 40 patients with untreated neuroblastoma, using a PCR-ELISA assay for telomerase activity. In these patients, 23 tumors had no or minimal telomerase activity whereas 15 had high levels of activity. In two tumors, telomerase activity was not assessable. There was significant correlation between the telomerase activity and MYCN copy number, 1p deletions, and TRK-A expression, as well as patient age, clinical stage, and outcome. The histological classification of the tumors was not significantly different between the two groups, being predominantly unfavorable by the Shimada classification. In addition, for 17 patients tumor tissue was assessed for telomerase activity post-chemotherapy. In those cases where the tumor was negative for telomerase activity before and after chemotherapy, the patients uniformly did well. In cases where the tumor was positive before and negative or weakly positive after treatment, two of the seven patients did well clinically. However, in cases that were positive after chemotherapy, all had recurrence or died. In conclusion, telomerase activity appears to be a prognostic factor for neuroblastomas. In addition, assessment of tumors post-chemotherapy may be a further indicator of clinical outcome.
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PMID:Telomerase activity as a prognostic factor in neuroblastomas. 1120 Apr 92

Aggressive neuroblastoma remains a therapeutic challenge, and additional understanding of its biology is of paramount importance. Changes in DNA-copy number were analysed in the neuroblastoma cells of 27 patients using comparative genomic hybridization (CGH). Eighteen of the patients had a poor risk disease (16/18 stage IV) and 9 had a non-poor-risk disease (3/9 stage I-II, 2/9 stage III, and 4/9 stage IVS). Changes in DNA-copy number were detected in 72% of the poor-risk and 22% of the non-poor-risk tumors with gains of chromosomal material being more prevalent than losses. Gains were most common in chromosomes 2, 7, and 17 and losses in chromosome 11. Changes in DNA-copy number were multiple in all but one of the patients with poor-risk disease. The applicability of CGH in studies on the genomic changes in pediatric malignancies is demonstrated by our data also adding weight to the argument of multiple elements with oncogenic and/or tumor suppressor potential being involved in the aggressive phenotype of poor-risk neuroblastoma.
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PMID:Comparative genomic hybridization reveals changes in DNA-copy number in poor-risk neuroblastoma. 1136 55

Neuroblastoma (NB), a malignant childhood tumor deriving from the embryonic neural crest, is sensitive to the growth-stimulating effects of insulin-like growth factors (IGFs). Aggressive cases of this disease often acquire autocrine loops of IGF production, but the mechanisms through which the different components of the IGF axis are regulated in tumor cells remain unclear. Upon conditional expression of c-Myb in a NB cell line, we detected up-regulation of IGF1, IGF1 receptor, and insulin-like growth factor-binding protein 5 (IGFBP-5) expression. Analysis of the IGFBP-5 promoter revealed two potential Myb binding sites at position -59 to -54 (M1) and -429 to -424 (M2) from the transcription start site; both sites were bound by c-Myb and B-Myb in vitro and in vivo. Reporter assays carried out using the proximal region of the human IGFBP-5 promoter demonstrated that c-Myb and B-Myb enhanced transcription. However, site-directed mutagenesis and deletion of the Myb binding sites coupled with reporter assays revealed that M2 but not M1 was important for Myb-dependent transactivation of the IGFBP-5 promoter. The double mutant M1/M2 was still transactivated by c-Myb, suggesting the existence of Myb binding-independent mechanisms of IGFBP-5 promoter regulation. A constitutively active AKT transactivated the IGFBP-5 promoter, whereas the phosphatidylinositol 3-kinase inhibitor LY294002 suppressed it. Moreover, the kinase dead dominant negative K179M AKT mutant was able to inhibit transcription from the M2 and M1/M2 IGFBP-5 mutant promoters. Deletion analysis of the IGFBP-5 promoter revealed that the AKT-responsive region lies between nucleotides -334 and -83. Together, these data suggest that the Myb binding-independent transactivation of the IGFBP-5 promoter was due to the activation of the phosphatidylinositol 3-kinase/AKT pathway likely mediated by IGF1 receptor-dependent signals. Finally, IGFBP-5 was able to modulate proliferation of NB cells in a manner dependent on its concentration and on the presence of IGFs.
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PMID:Expression of insulin-like growth factor-binding protein 5 in neuroblastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms. 1197 31

Human neuroblastoma (NB) tumors elaborate angiogenic peptides, and enhanced angiogenesis correlates with their aggressive behavior, metastatic spread and poor clinical outcome. Hence, inhibition of angiogenic factor production may represent a potential therapeutic target for NB treatment. There is currently little information regarding the stimuli that control NB production of angiogenic mediators. In this study, we analyzed the effects of hypoxia, a common feature of solid tumors and a major drive to tumor angiogenesis, and of PA, a tryptophan catabolite produced under inflammatory conditions and endowed with several biologic properties, on the production of the angiogenic activator VEGF by advanced-stage human NB cell lines. We demonstrate that both stimuli are potent inducers of VEGF expression and secretion. VEGF upregulation by PA involved iron chelation because iron sulfate prevented this effect whereas the iron-chelating agent DFX induced VEGF production. Conversely, the CDK inhibitor Flp completely blocked VEGF induction by hypoxia. This effect occurred as early as 3 hr after stimulation and did not require de novo protein synthesis. Moreover, Flp exerted similar inhibitory activity on VEGF induction by PA or DFX, suggesting that this compound targets an essential step in the signaling pathway that leads to VEGF expression. Our findings demonstrate that PA can modulate angiogenic factor production by tumor cells and establish the importance of Flp as an inhibitor of VEGF production by human NB.
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PMID:Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma. 1211 98


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