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)

Fifteen children with metastatic neuroblastoma resistant to vincristine and cyclophosphamide were treated with two drugs which were known to be effective as single drugs against neuroblastoma. The drugs were given in courses every 3 weeks. Doxorubicin (50 mg/m2 iv) was given on Day 1 and cisplatin (50 mg/m2) was administered on Day 2 as an 8-hour infusion, using a forced diuretic-hydration program. Three of the 15 children achieved partial or complete remission. Three children showed improvement. The other children either did not respond to the therapy or had progressive disease. The combination of doxorubicin and cisplatin given in the sequence outlined is no more effective than either drug given singly. The side effects of the drug combination were tolerable and were in keeping with previously described toxicity.
 ...
PMID:Doxorubicin and cisplatin therapy in children with neuroblastoma resistant to conventional therapy: a Southwest Oncology Group Study. 702 53

A 1-year-old male infant showed cerebellar signs and symptoms, and excess urinary excretion of vanillylmandelic acid (VMA). Each of them disappeared spontaneously but a large abdominal tumor occurred at 3 years of age. Surgical specimen of the tumor was diagnosed as neuroblastoma and the patient died at 4 years of age. Autopsy revealed the huge tumor originated from the right adrenal, and occupying the retroperitoneum, pelvic cavity and posterior mediastinum. Histology of the primary lesion was chiefly that of ganglioneuroma, while all of the metastatic ones neuroblastoma. Transitional histology from neuroblastoma to ganglioneuroma was also observed in the primary lesion. The diagnosis was designated as composite ganglioneuroblastoma. The surgical material of the metastatic neuroblastoma was cultured for 2 months in vitro and the tumor cell clumps extended spontaneously abundant long neurites. This phenomenon suggests the high maturation ability of the neuroblastoma cells.
 ...
PMID:Composite ganglioneuroblastoma--a case report and short term culture of tumor cells. 736 44

Examination of a large, oedematous placenta of a still-born infant showed an extensive infiltration of chorionic villi by malignant cells; the nature of these was not apparent by light microscopy. Ultrastructural examination of these cells showed the presence of cytoplasmic granules whose size and appearance were consistent with those characteristically present in neuroblastomas. Whereas no necropsy was carried out on the still-born infant, it may be assumed, in keeping with the available data, that the placental metastases were derived from a congenital neuroblastoma. Infiltration of the villous stroma by metastatic neuroblastoma observed in the present case was not reported previously as in all other known instances the metastatic neuroblastomatous cells were confined to the lumina of the chorionic vessels.
 ...
PMID:Placental infiltration in congenital neuroblastoma: a case study with ultrastructure. 742 28

Although infants (age less than 1 year) with neuroblastoma have a favorable overall prognosis, metastatic disease is associated with poorer treatment outcome. To assess the role of surgery in these patients, the authors reviewed survival data for 151 infants treated for neuroblastoma, focusing on patient and tumor characteristics, biological markers, and surgical management among the 99 patients with metastatic disease. Patients were divided into early (1961 to 1978) and contemporary (1979 to 1993) treatment eras. Potential prognostic factors were statistically tested to determine their significance in affecting survival. Five-year survival by Pediatric Oncology Group stage was: A, 100% (+/- 0%); B, 94% (+/- 6%); DS, 77% (+/- 9%); C, 73% (+/- 9%); and D, 61% (+/- 8%). Survival for infants with metastatic disease (stages C, D, and DS) was affected significantly by treatment era (P = .0001). Analyses restricted to patients treated during the contemporary era showed prognostic significance for DNA index (P = .02), N-myc copy number (P = .007), serum lactate dehydrogenase level (P = .001), and extent of resection (P = .01). A > or = 95% resection of the primary tumor was found to be associated with improved survival. Significantly more surgical complications were associated with resections performed at the time of diagnosis (P = .007), and delaying surgery until after several courses of chemotherapy did not decrease survival. In conclusion, multiple factors affect the outcome of treatment for infants with metastatic neuroblastoma, and whenever feasible, a > or = 95% resection of the primary tumor should be performed in this patient subgroup.
 ...
PMID:Infants with metastatic neuroblastoma have improved survival with resection of the primary tumor. 747 48

Retinoic acid has considerable potential for the chemoprevention and chemotherapy of cancer. Neuroblastoma cells differentiate in response to retinoic acid in vitro, an observation that has led to clinical trials using either the 13-cis or all-trans isomers of retinoic acid. We review the effects of retinoic acid on neuroblastoma, and the potential involvement of nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). 9-cis retinoic acid is a ligand for RXRs, and we review recent data on the differential effects of 9-cis and all-trans retinoic acid on neuroblastoma differentiation and proliferation in vitro, and possible mechanisms of action via hetero- and homodimers of RARs and RXRs. Although there is uncertainty whether or not 9-cis retinoic acid produces its biological effects primarily via RXR homodimers, in vitro data suggest that this isomer of retinoic acid or stable analogues may have considerable potential for the treatment of resistant, disseminated neuroblastoma.
 ...
PMID:Gene expression and neuroblastoma cell differentiation in response to retinoic acid: differential effects of 9-cis and all-trans retinoic acid. 757 51

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.
 ...
PMID:Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma. 757 63

Knowledge about genetic alterations specific to the metastatic process and chemoresistance in neuroblastoma is progressing steadily. Low or no CD44 expression, increased NM23 expression and specific mutations of the 5' coding regions of NM23 are distinct features of aggressive, metastatic neuroblastoma. MYCN down-regulates Class I HLA antigen expression in many neuroblastoma cell lines and, in turn, may be regulated by a suppressor gene. The MYCN amplified human neuroblastoma cell line, IGR-N-91, established in vitro, metastasises in the nude mouse and has exhibited co-activation of MYCN and PGY1, resulting from direct activation of the oncoprotein on the PGY1 promoter. In this model, the MYCN product activates angiogenesis, the dissemination process and chemoresistance via specific genes (PGY1 and GST3). MYCN, like the BCL-2 and TP53 products, may also play a key role in apoptosis. The implication of these genes in the potential for metastasis and chemoresistance in neuroblastoma is discussed.
 ...
PMID:Genetic alterations associated with metastatic dissemination and chemoresistance in neuroblastoma. 757 68

A recent Consensus Conference in Lyon reviewed the role of high-dose therapy with stem cell rescue in a variety of malignancies including childhood tumours. The conclusion was that with the exception of metastatic neuroblastoma there is still no proven role for this treatment strategy. It is more than 10 years since this approach was used in neuroblastoma and it has subsequently been applied to most of the common childhood solid tumours. Although a single randomised study has suggested that the progression-free survival is significantly prolonged with high-dose melphalan, the superiority of this over continued intensive conventional therapy is unclear. It seems likely that a selected subgroup of children with stage IV disease may benefit from megatherapy and the results of current randomised trials are awaited. In rhabdomyosarcoma, the duration of treatment may be shortened by dose escalation, but the impact on the outcome in very high-risk patients remains unproven. In Ewing's sarcoma, there has been difficulty defining high-risk patients, but recent studies suggest that megatherapy may have a role in patients with bone or bone marrow disease who have little chance of long-term survival with conventional chemotherapy approaches. In brain tumours, the results have been disappointing for gliomas, but there is currently enthusiasm about a possible role in the chemosensitive primitive neuroectodermal tumours. In this group of diseases which are inherently chemosensitive, the poor results from chemotherapy in the past have resulted from a failure to achieve appropriate drug levels at the tumour site and this may be potentially overcome by dose escalation. In Wilms' tumour, although the overall cure rate is very high, there appears to be a useful role for megatherapy in certain high-risk relapsed patients who have little chance of cure with conventional salvage therapy. There is an urgent need for international collaboration to design randomised studies which will as rapidly as possible address the issue of the role of these expensive and high morbidity procedures in childhood cancer.
 ...
PMID:Intensive chemotherapy with stem cell support-experience in pediatric solid tumours. 762 56

We have investigated whether retroviral mediated transfer of the IL-2 gene renders human neuroblastoma cells immunogenic, justifying their use in a clinical tumor immunization study. Fourteen neuroblastoma cell lines were established from patients with disseminated neuroblastoma and transduced with the vector G1Ncvl2, which contains the neomycin phosphotransferase gene and the cDNA of the human interleukin-2 gene. Clones secreting > 150 pg/10(6) cells/24 h of IL-2 were selected for further study. Secretion of IL-2 was maintained for at least 3 weeks in nonselective media, implying that production of the cytokine would continue under in vivo conditions. Co-culture of IL-2 transduced cell lines with patient lymphocytes induced potent cytotoxic activity against both transduced and parental neuroblastoma cell lines. This activity was HLA unrestricted, and predominantly mediated by CD16+ or CD56+ and CD8- lymphocytes. These data form the preclinical justification for our current immunization protocol for patients with relapsed or resistant neuroblastoma.
 ...
PMID:Immunomodulatory effects of human neuroblastoma cells transduced with a retroviral vector encoding interleukin-2. 762 15

Neuroblastoma is an uncommon malignant neoplasm that derives from neural crest progenitor cells that normally give rise to the sympathetic nervous system. It represents 8 to 10% of all extracranial tumors in childhood. The purpose of this paper is to report a case in which a mandibular soft tissue mass was the initial presenting sign of disseminated neuroblastoma in a 2-year-old child, and to discuss the clinicopathologic features and biologic behavior of neuroblastoma.
 ...
PMID:Disseminated neuroblastoma with initial presentation as an intraoral mass: case report. 793 66


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