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 a childhood cancer which originates in the embryonic tissue of the developing sympathetic neural crest. In 1972, Dr. A. Knudson hypothesised a similar 'two-hit mutation' model for the origin of neuroblastoma as for retinoblastoma and Wilms tumor. In this model, malignant cell growth is caused by mutations of both alleles of a tumor suppressor gene. In hereditary tumors, a germinal mutation is present in all cells of the individual, a mutation of the remaining allele by a somatic hit causes loss of gene function. Sporadic tumors result from two somatic mutations of a tumor suppressor gene involving both alleles within the same cell. The occurrence of patients with a constitutional chromosomal deletion syndrome in association with tumor facilitated the cloning of a retinoblastoma gene and of a Wilms tumor suppressor gene. In neuroblastoma, cytogenetic and molecular studies suggest the existence of a neuroblastoma (suppressor) gene at chromosome 1, at subband 1p36. A constitutional chromosomal deletion syndrome was not known for neuroblastoma. We described a constitutional chromosome translocation t(1;17)(p36.31-21; q11.2-12) in a patient with neuroblastoma. We hypothesised that this translocation, involving the chromosomal band 1p36, predisposed the patient to neuroblastoma development by disturbance of a gene located at the translocation breakpoint. Consequently, identification of the breakpoint flanking markers can be an important step towards the identification and cloning of a neuroblastoma suppressor gene. Radioactive in situ hybridization methods were first applied on the patient's fibroblasts. Soon it became evident that cells with better growth characteristics were needed and that the availability of sufficient patient material was essential. Therefore a somatic cell fusion experiment was performed between the patient's fibroblasts and a thymidine kinase-deficient Chinese hamster cell line. Somatic cell hybrid clones were selected on the presence of the derivative human chromosomes 1 and 17, and of the normal homologues. With the use of fluorescence in situ hybridisation (FISH), the position of chromosome 1 and chromosome 17 markers respective to the breakpoints was determined on chromosome metaphases of the hybrid cell lines containing the human derivative chromosomes. The pronatriodilatine (PND) and the adenovirus 12 modification site (A12M2) were identified as distal and proximal 'single copy' flanking markers of the chromosome 1 breakpoint, respectively. The chromosomal break occurred in a highly repetitive region containing an adenovirus modification site and genes encoding transfer RNA and small U1-RNA genes. The breakpoint on chromosome 17 is located in a region with as proximal boundary the distal part of the neurofibromatosis 1 (NF1) gene locus and as distal flanking marker the SCYA7 locus, encoding the monocyte chemotactic protein-3. Southern blot analysis showed no rearrangements of hybrid DNA using single copy probes for the four flanking markers. Identification of the four breakpoint flanking markers on chromosomes 1 and 17 constitutes a pivotal step for the cloning of the translocation breakpoints and for the identification of a presumed neuroblastoma suppressor gene.
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PMID:[Identification of the breakpoint-flanking markers on chromosomes 1 and 17 of a constitutional translocation T(1;17)(P36;Q12-21) in a patient with neuroblastoma]. 857 70

The causes of most childhood cancer remain elusive; some children clearly have a genetic predisposition, but in the majority the relative contributions of environmental and host factors are not established. One approach to this question is through twin concordance studies, but only the most common malignancy, acute leukemia, has been studied to date, owing to the rarity of other forms of childhood cancer. The aim of the study was to determine the concordance rates for childhood cancer in twins, in order to clarify the importance of constitutional predisposition for a range of tumor types. Twins with cancer were ascertained through three cooperative clinical trials groups, a cancer-twin registry, and a large pediatric hospital. Subjects were sent a postal questionnaire requesting information on cancer concordance and zygosity. Data were obtained on 556 twins with cancer. Three twin pairs, out of 197 twin pairs (76 monozygous, MZ, twin pairs), were concordant for leukemia, giving an MZ case-wise concordance rate (5%) that is substantially lower than previously reported. The case-wise concordance for non-retinoblastoma solid tumors was 2.2%: Two twin pairs were concordant for CNS tumors, one was concordant for neuroblastoma, and two twin pairs were concordant for cancer but not for the type of cancer. The results of the present study, together with previous data from population studies of siblings and offspring, suggest that there is not in general a strong constitutional genetic component for childhood cancers other than retinoblastoma.
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PMID:Concordance for childhood cancer in twins. 860 Mar 32

Neuroblastoma (NB) is a childhood cancer of the autonomic nervous system. The molecular pathology of NB is not yet well understood. Both amplification of the proto-oncogene N-myc and loss of heterozygosity of several chromosomal loci occur in NB, representing genetic instability. In this study, we examined another type of genetic instability, microsatellite instability. Five chromosomal loci known to exhibit this alteration in colon, gastric, and pancreatic cancers were used in a PCR-based assay to examine 30 matched normal and tumor DNAs, which included all stages of tumor progression. Among these 30, only 2 (7%) manifested microsatellite instability. There was no correlation between the occurrence of microsatellite instability and the amplification of the N-myc gene. These data show that microsatellite instability is infrequent in neuroblastoma tumors.
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PMID:Microsatellite instability is infrequent in neuroblastoma. 863 65

The data of a survey undertaken to record all cases of childhood cancer in Namibia from 1983 to 1988 were analyzed to estimate 5-year survival rates. The projected survival rate for 150 children with cancer was 37%, with no difference between boys and girls. The calculated survival rates for most of the tumor groups were poor with the exception of Wilms' tumor which had a 5-year survival rate of 76%. The zero survival rate of children with malignant bone disease may have been due to inadequate treatment. Neuroblastoma and retinoblastoma presented with advanced disease, which contributed to the poor survival rates of 13% and 46%, respectively. The overall survival rate for lymphoma of 53%, and of 39% for all leukemias, compares poorly with the rates obtained in industrialized countries. The relatively poor 25% survival rate for tumors of the central nervous system may partly be due to the long delay between the initial diagnosis and the institution of appropriate treatment for raised intracranial pressure and for the tumor. Both cure and longterm follow-up are difficult to achieve in a developing country. Improved early diagnosis and appropriate treatment are necessary to improve survival rates.
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PMID:Outcome of children treated for cancer in the Republic of Namibia. 869 93

Neuroblastoma is perhaps the most heterogeneous childhood cancer in terms of clinical behavior. Stage of disease, age at diagnosis, levels of urinary catecholamine excretion, N-myc amplification, and DNA ploidy have been found to be significant prognostic factors. The aims of this combined retrospective-prospective study are to verify the prognostic significance of DNA ploidy and to show its correlation with other prognostic signs. Thirty six fresh and thirty three paraffin embedded samples from patients with histologically confirmed neuroblastoma (41 prior to receiving any chemotherapy) were available for flow cytometry DNA analysis. Our results showed that the maturation induced during chemotherapy could give rise to aneuploidy therefore we analyzed the associations between the DNA ploidy and other prognostic markers only in patients examined before chemotherapy. There were no significant correlations between DNA ploidy and urinary catecholamine metabolites levels or tumor localization. DNA aneuploidy was significantly more frequent in patients with lower clinical stage, lower age at diagnosis, and without N-myc gene amplification. Patients with DNA aneuploid neuroblastomas died less frequently than patients with DNA diploid tumors. There were no significant associations among the S-phase or proliferation fraction and other prognostic factors.
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PMID:DNA ploidy in neuroblastoma. 884 55

The total incidence of childhood cancer varies rather little between different regions of the world, with cumulative risk to age 15 nearly always in the range 1.0-2.5 per thousand. Acute lymphoblastic leukaemia, especially in early childhood, is most common in populations of high socio-economic status and is the most frequent childhood cancer in all industrialised countries. The risk of Burkitt's lymphoma is highest in tropical Africa and Papua New Guinea; it is strongly associated with Epstein-Barr virus infection and intense immune stimulation by malaria. Other lymphomas are also relatively common in developing countries. Non-heritable retinoblastoma has a higher incidence among less affluent populations, suggesting an association with poor living conditions and maybe an infectious aetiology. In contrast, the incidence of Wilms' tumour and Ewing's sarcoma varies largely on ethnic lines, indicating a strong role for genetic predisposition. Much of the variation in recorded incidence of brain tumours and neuroblastoma may be due to varying levels of case ascertainment. Recently the incidence of childhood Kaposi's sarcoma has risen substantially in parts of Africa severely affected by the AIDS epidemic.
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PMID:Geographic and ethnic variations in the incidence of childhood cancer. 903 26

Neuroblastoma is a pediatric cancer for which a cure is elusive for most children with disseminated disease. Neuroblastomas possess receptors for somatostatin (SS). Some SS analogues can inhibit their proliferation. In addition, when SS analogues were used as agents for scintigraphy, neuroblastoma tumor sites can be localized with high efficiency. In this study, to better characterize the SS receptor subtype(s) (sst1-5) present in primary tumors and metastases of neuroblastoma, we show that: (1) The ligand 125I-Tyr11-SS-14 binding on membrane proteins from primary tumors and metastases of neuroblastoma cell line IGR-N-91 developed in nude mice shows similar values of Kd (in order of 0.1 nM) and Bmax (in order of fmol/mg) by filter-retention assay. These data are close to those measured on two other neuroblastoma cell lines: SK-N-SH and IGR-N-835 or to that measured on the rat cerebral cortex. (2) The IGR-N-91 sublines derived from primary tumor and metastases show one major complex of 57 kD by the chemical cross-linking assay using the ligands: 125I-SS-14 and 125I-BIM23014. One similar major complex of 57 kD was also detected in SK-N-SH and IGR-N-835 or in the cerebral cortex. (3) Addition of excess nonlabeled peptides selective for sst2 (BIM23014, BIM23060, BIM23068) suppressed the formation of the complex 57 kD whereas addition of BIM23052 or BIM23056 (sst5 and sst3 selective respectively) does not. This pharmacological profile corresponds to sst2. (4) Only RNA message of sst2 gene is detected in IGR-N-91 cells and its metastases derived sublines by reverse-transcription-polymerase chain reaction and Northern hybridization in keeping with the presence of sst2. (5) In human biopsies, the complex of 57 kD corresponding to sst2 is consistently detected in three samples of the histological subset of the disease: benign ganglioneuroma, ganglioneuroblastoma and immature neuroblastoma. Therefore, the sst2 should be considered as the primary target to develop more potent SS analogues for neuroblastoma therapy or/and scintigraphy.
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PMID:Somatostatin-14 mainly binds the somatostatin receptor subtype 2 in human neuroblastoma tumors. 905 84

The dose-effect relationship in pediatric oncology conventional chemotherapy is emphasized. Rationales for the use of megatherapy protocols with stem cell support and associated procedures are given. It has been more than 15 years since this approach was used in neuroblastoma, and it has subsequently been applied to most of advanced, common childhood solid tumors. The ongoing use of new strategies for dose intensification with peripheral blood stem cell or autologous purged bone marrow rescue has raised expectations for cure. To date, results of megatherapy followed by autologous stem cell reinfusion are encouraging in metastatic neuroblastoma and Ewing's sarcoma, with an increase in event-free survival rates of about 30% as compared with that of conventional treatments. However, with the exception of metastatic neuroblastoma, there is still no proven role for this treatment strategy. Thus, there is still an urgent need for international collaboration to design randomized studies that could rapidly address the issue of these expensive and high-morbidity procedures in childhood cancer.
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PMID:Autologous stem cell transplantation for solid tumors in children. 908 57

Amifostine (WR-2721) is currently being investigated as a potential protector of normal tissues during chemotherapy in adult and pediatric cancer patients. The marked reduction of bone marrow and renal toxicity by amifostine is well documented, but data are lacking whether the anticancer activity of cytostatic drugs is also preserved in neuroblastoma as the second most common pediatric malignancy. We investigated the cytotoxic effect of six drugs on two neuroblastoma cells lines chosen for their presence or absence of N-myc amplification and PGY1 overexpression: IMR-5 (N-myc 25 x, PGY1-negative), CHP-100 (N-myc 1x, PGY1-positive) in vitro in the presence and absence of WR-2721 and its active metabolite WR-1065 using the monolayer proliferation assay. Doxorubicin, vincristine, etoposide, cisplatin, 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide were equally cytotoxic with and without preincubation of WR-2721 (14 mM) or WR-1065 (40 microM) as shown by virtually identical dose-response curves and ID50 values. We conclude that WR-2721 and WR-1065 did not reduce the cytostatic activity of six commonly used drugs on neuroblastoma cell lines in vitro.
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PMID:Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in vitro. 914 9

In the framework of the ITACARE project, a cooperative investigation conducted on the data from the Italian population-based cancer registries, survival of patients with childhood malignant neoplasms was studied. The study included 1,768 cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19. Cases were collected over the period 1978-1989, or more limited periods for some participating registries. A total of 1,138 cases were from the Childhood Cancer Registry of Piedmont and 659 from the registries operating in the provinces of Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the cities of Genova and Torino (the last contributed only for bone neoplasm diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986-1989. The range among registries of 5-year survival for cases diagnosed in 1986-1989 was 55-78%. Most diagnostic categories presented an improved prognosis for the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for retinoblastoma. Italian survival was similar to that observed in other population-based surveys in the UK and USA.
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PMID:Survival of childhood cancer patients in Italy, 1978-1989. ITACARE Working Group. 915 68


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