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

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.
 ...
PMID:Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification. 228 1

Shedding of membrane gangliosides is characteristic of human and experimental tumors. Because some shed tumor gangliosides have potent tumor-enhancing properties, significant ganglioside shedding could influence tumor progression. We examined this possibility in a human tumor, neuroblastoma. Ganglioside shedding, measured as circulating tumor-derived GD2 ganglioside, and the outcome of 74 patients with advanced stage (III and IV) disease were studied. Progression-free survival (PFS) was inversely related to circulating GD2 levels at the time of diagnosis (P = .018). By Kaplan-Meier analysis, the quartile of patients having the highest circulating GD2 levels (greater than or equal to 568 pmol/mL) had a strikingly different outcome from the quartile of patients with the lowest (less than or equal to 103 pmol/mL) GD2 levels (P = .013): median PFS was shorter (9 v 28 months), and the long-term survival rate lower (2-year PFS of 24% v 70%). We conclude that more rapid disease progression and lower survival rate are associated with high circulating GD2 levels at diagnosis and speculate that shed neuroblastoma tumor gangliosides play a role in accelerating tumor progression.
 ...
PMID:Shed tumor gangliosides and progression of human neuroblastoma. 231 62

Amplification of the N-myc oncogene is detected in about 30% of untreated neuroblastomas. Amplification is associated with advanced stages of disease and rapid tumor progression. However, it was not known if the N-myc copy number was homogeneous in tumor tissue of an individual patient, or if it changed with time in vivo. Therefore, we have made 66 observations on multiple simultaneous or consecutive tumor samples from 60 patients with neuroblastoma. (a) Simultaneous samples were obtained from different areas of 31 tumor masses from 30 patients: a similar N-myc copy number (1-2, 3-10, or greater than 10) was found in all samples from each patient. (b) Simultaneous samples were obtained from different anatomical sites in ten patients. No difference in N-myc copy number was seen. (c) Finally, 25 patients had two or more tumor samples obtained over time. Thirteen patients had a single copy of N-myc in all samples, and 12 had consistent levels of amplification in all samples. Two of the latter cases had single copy of N-myc in a second-look surgery sample, but no tumor was evident histologically. This study demonstrates that the N-myc copy number in human neuroblastomas is usually consistent within a tumor, not only at different tumor sites, but also at different times in vivo. Overall, these findings suggest that N-myc amplification is an intrinsic biological property of a subset of neuroblastomas, and if amplification is going to occur, it is generally present at the time of diagnosis.
 ...
PMID:Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients. 244 May 61

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.
 ...
PMID:Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. 248 76

Human neuroblastomas are characterized cytogenetically by manifestations of gene amplification and by partial monosomy for the short arm of chromosome 1. Analysis of 646 neuroblastomas and 16 ganglioneuromas showed N-myc gene amplification in only seven of 169 (4%) with low stages of disease but in 138 of 436 (32%) with advanced stages of disease. N-myc amplification was seen in four of 41 (10%) stage IV-S tumors, and none of 16 ganglioneuromas. Analysis of patient survival by stage, age, and N-myc copy number indicate that N-myc amplification was highly correlated with rapid tumor progression, even in patients with low stages of disease. Partial monosomy of chromosome 1p can be more effectively detected by analysis of restriction fragment length polymorphisms to detect somatic loss of heterozygosity (LOH) for chromosome 1p, which is the molecular equivalent of chromosome deletion. Analysis of pairs of normal and tumor DNAs from patients with neuroblastoma demonstrated that 13 of 47 tumors (28%) had LOH at one or more loci on distal chromosome 1p; the region that shows LOH most consistently is between 1p36.1 and 1p36.3. LOH for 1p shows a highly significant correlation with N-myc amplification, suggesting that these two genetic events are related and characterize a genetically distinct subset of aggressive neuroblastomas.
 ...
PMID:Clinical significance of genetic rearrangements in human neuroblastomas. 237 69

A large number of studies have investigated the relationship between the long-term survival and the percentage of tumor cells in S phase assessed by autoradiography after tritiated thymidine labelling, image cytometry, flow cytometry or labelling with an halogenated analog of thymidine, in various types of human solid tumors. The survey of the results clearly shows that the S-phase fraction (SPF) is of high prognostic significance in several types of cancers, in particular in breast cancers, non-Hodgkin lymphomas, ovarian cancers, neuroblastoma, bladder cancers and lung cancers. SPF was found of high independent significance in 10 of the 11 studies in which multivariate analyses of prognostic factors had been carried out. Proliferation appears generally to be of higher prognostic significance than ploidy. In view of the wide differences in the biological characteristics of the tumors studied, it is likely that the association between a high proliferation rate and the degree of tumor aggressiveness is a general feature of human solid tumors. However, high proliferative rate of tumor cells is probably not the cause of tumor biological aggressiveness but a variable associated with it. The extent to which cells escape from the regulatory systems which control their proliferation appears to be a good index of tumor progression.
 ...
PMID:Cell proliferation kinetics in human solid tumors: relation to probability of metastatic dissemination and long-term survival. 266 9

The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. We have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 21 melanoma cell lines to analyze the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples from a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.
 ...
PMID:Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. 273 11

Activation of cellular proto-oncogenes can be detected in several human cancers. In neuroblastoma, amplification and overexpression of N-myc oncogene have been shown to be associated with advanced stages of disease and rapid tumor progression. These results suggest the clinical importance of the N-myc oncogene. Other oncogenes might also be activated in this cancer.
 ...
PMID:[Prognostic value of the N-myc oncogene in neuroblastoma]. 316 15

Patients with neuroblastoma who present with the syndrome of opsoclonus and myoclonus enjoy a remarkably good prognosis independent of their stage of disease or their age at diagnosis. The presence of N-myc amplification also has been found to be an independent prognostic factor in neuroblastoma. Patients with multicopy N-myc tumors have rapid tumor progression whereas those with single-copy tumors have a significantly better progression-free survival. The authors examined four primary, untreated neuroblastomas for the N-myc copy number from patients who presented with opsoclonus and myoclonus. All four tumors had single copies of N-myc, and all four patients are alive with no evidence of recurrent disease with 6+ to 54+ months' follow-up. This appears to be the only report of N-myc analysis in this group of children. It would be interesting to analyze more neuroblastomas from patients who present with opsoclonus and myoclonus to determine how many of these patients have single N-myc copy tumors.
 ...
PMID:Single copies of the N-myc oncogene in neuroblastomas from children presenting with the syndrome of opsoclonus-myoclonus. 339 55

Retrospective quantitative DNA analysis was done on 147 samples from 89 patients with neuroblastoma and ganglioneuroma using flow cytometry. In the neuroblastoma patients, nuclear DNA content was found to be a stable tumor marker irrespective of site (primary versus metastatic) and despite changes with time in tumor progression, maturation, or therapy. The occurrence of DNA aneuploidy, which was detected in 60% of the neuroblastoma patients, paralleled other favorable indicators and was highly associated with survival (P less than 0.001). Of clinical stage, age, primary site, sex, and DNA content, only stage and DNA content correlated with survival. Those patients with favorable stage and DNA aneuploidy had higher survival rates. Further, favorable stage and the presence of DNA aneuploidy were independent prognostic indicators. Abnormal DNA content was also detected in samples from ganglioneuromas in which significant numbers of ganglion cell nuclei were recovered. These results indicate a striking difference between neuroblastoma and adult tumors in which DNA aneuploidy is generally a poor prognostic sign and provide a molecular link between ganglioneuromas and their malignant counterparts.
 ...
PMID:Flow cytometric DNA analysis of neuroblastoma and ganglioneuroma. A 10-year retrospective study. 339 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>