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)

The observed response of [131I]metaiodobenzylguanidine (131I-MIBG) therapy in advanced neuroblastoma after conventional therapy had failed, the noninvasiveness of the procedure, and the high metabolic activity of untreated tumors led to a new protocol to use 131I-MIBG therapy in newly diagnosed patients instead of combination chemotherapy prior to surgery. The objectives of this study are to improve the overall outcome of patients with neuroblastoma by introducing 131I-MIBG therapy as the first therapy in the treatment schedule, in order to reduce the tumor volume, enabling adequate surgical resection and avoiding toxicity and the induction of early drug resistance. The advantages of this approach are that the child's general condition is unaffected before surgical resection is performed and that chemotherapy is reserved to treat minimal residual disease. So far, 13 patients with inoperable neuroblastoma (stage III and IV) were treated with 131I-MIBG initially and then submitted to surgery. More than 50% decrease of the volume of the primary tumor was noted in 7 of 10 evaluable patients; 8 patients have so far been operated with complete resection in 2, greater than 95% resection in 5 and 80% resection in one patient. Three patients are still undergoing 131I-MIBG treatment. The toxicity of 131I-MIBG de novo is in contrast with the previous experience of 131I-MIBG therapy after conventional therapy: only 4 patients had thrombocytopenia and only 1 of 7 patients with bone marrow involvement developed bone marrow depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preoperative [131I]metaiodobenzylguanidine therapy of neuroblastoma at diagnosis ("MIBG de novo"). 182 28

Autologous bone marrow transplantation (ABMT) allows delivery of intensive, marrow-ablative chemotherapy or chemoradiotherapy to children with high-risk solid tumors. Results from several studies of neuroblastoma suggest that outcome is improved by ABMT; however, relapses can occur months to years after complete clinical remission. Other high-risk tumors including peripheral neuroepithelioma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, and brain tumors also appear to be responsive to intensive marrow-ablative therapy, although few studies have been reported. For tumors that can metastasize to marrow, a sensitive method is necessary for detecting tumor cell contamination. Immunocytologic analysis with monoclonal antibodies can identify one neuroblastoma cell per 10(5) normal marrow cells; this method also is applicable to other tumors with appropriate antibodies. Ex vivo removal (purging) of tumor cells decreases the probability of infusing tumorigenic cells with the ABMT. There is considerable experience in tumor detection and purging for neuroblastoma, but little has been done for other childhood solid tumors. Future investigations of ABMT will aim to further increase disease-free survival by intensifying induction and marrow-ablative regimens and by developing therapies to be given after ABMT that are directed at minimal residual disease. As pilot investigations mature, the efficacy of ABMT and conventional chemotherapy will be compared in multi-institution randomized studies.
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PMID:Treatment of high-risk solid tumors of childhood with intensive therapy and autologous bone marrow transplantation. 200 84

Fifteen patients with olfactory neuroblastoma were treated during the 17-year period of 1969 to 1986. Data was analyzed with respect to age at presentation, sex, presenting signs and symptoms, stage, and results of treatment. Age ranged from 4 to 67 years with the median age being 27 years. Median follow-up was 8 years. Local control was achieved in nine of nine patients or 100% with successful surgical resection, i.e., minimal residual disease, followed by postoperative radiation therapy (45 to 65 Gy) was employed. There were no distant failures when the primary site was controlled. Regional lymph node metastases were infrequent: only 13% (two of 15 patients) presented with positive nodes. Three of four patients treated initially with surgery alone had a local recurrence, two of which were successfully salvaged by combined therapy. There were four patients treated with radiation therapy alone: three had persistent disease after radiation therapy, and one patient was controlled with 65 Gy. Olfactory neuroblastoma has a propensity to recur locally when treated with surgery alone. The authors' experience suggests excellent local control can be achieved with surgery immediately followed by radiation therapy. Thus the authors recommend planned combined treatment for all resectable lesions.
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PMID:Olfactory neuroblastoma. 272 May 89

Eighty bone marrow studies (each including 4 aspirates and 4 trephine biopsies) were performed in 37 children with stage IV neuroblastoma to assess the most accurate means for detection of invasion by neuroblastoma cells. Among 38 abnormal results, only trephine biopsy(ies) were found positive in 24 cases (63%), only aspirate(s) in 5 cases (13%), and both in 9 cases (24%). In 37% of abnormal results, only 1 of the 8 tests performed was found positive. No benefit was obtained from either associated touch imprints of iliac biopsies (67 investigations), or exploration of extra-iliac sites (66 sternums, 53 tibias). Two monoclonal antibodies, claimed to be specific for detection of neuroblastoma cells in bone marrow, were used in 56 investigations; they could detect minimal residual disease in some cases, but they were unreliable when no staining was obtained if initial phenotype of neuroblastoma had not been assessed, or when few isolated cells were observed. Prospective studies using immunocytology and immunohistology are thus warranted.
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PMID:[Detection of residual cells contaminating the bone marrow in neuroblastoma. Apropos of 80 bone marrow evaluations]. 344 68

Neuroblastoma is the most common solid extracranial tumour in childhood. In spite of intensive efforts of clinicians and scientists the prognosis for advanced disease is still poor. This paper presents a short review of the state-of-the-art in conventional treatment including surgery, chemotherapy, and radiation. This is followed by a review of the treatment attempts with high dose chemotherapy followed by autologous bone marrow or stem cell transplantation. One of the main problems with this approach is the contaminating tumour cells. Finally the various immunotherapeutic strategies are summarised which are used to remove minimal residual disease. Later, our new approach, combining various treatment modalities, is described.
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PMID:Clinical strategies for the treatment of neuroblastoma. 757 70

The observed response to 131I-metaiodobenzylguanidine (MIBG) therapy in advanced neuroblastoma after conventional therapy, the non-invasiveness of the procedure, and the high metabolic activity which is frequently observed in untreated tumours led to the concept of substituting 131I-MIBG therapy for combination chemotherapy at diagnosis prior to surgery in patients with advanced disease/high-risk neuroblastoma. The objective of introducing 131I-MIBG therapy as the first therapy in the treatment schedule is to reduce the tumour volume, enabling adequate (> 95%) surgical resection of the tumour and to avoid toxicity and the induction of early drug resistance. The advantages of this approach are that the child's general condition is unaffected or improved before it undergoes surgical resection and that chemotherapy is reserved to treat minimal residual disease postoperatively. Thirty-one children who presented with inoperable neuroblastoma (10 Evans stage III, 21 stage IV) were treated according to this protocol. The objective response to the 131I-MIBG therapy at diagnosis with respect to the volume of the primary tumour, the metastases and catecholamine excretion in urine varied from 72 to 81%, which is better than after conventional treatment. Nineteen of 27 evaluable patients (70%) had complete or > 95% resection of the primary tumour or did not require surgery at all. Only 11 of 31 patients developed isolated thrombocytopenia and, despite the fact that the bone marrow was invaded in 16 patients, moderate bone marrow depression occurred in only two cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:131I-MIBG as a first-line treatment in high-risk neuroblastoma patients. 781 84

The use of differentiation-inducing agents has been proposed for the purging of bone marrow and for the treatment of minimal residual disease prior to autologous bone marrow transplantation in patients with metastatic neuroblastoma. The present studies examine the effects of the enediyne differentiation inducer neocarzinostatin (NCS) on tumor development from subcutaneous implants of murine (Neuro-2A) neuroblastoma cells. Prior in vitro treatment with NCS results in a concentration- and drug exposure time-dependent decrease in the incidence of tumors from subcutaneously implanted cells. In vivo treatment results in a dose-dependent decrease in the rate of tumor growth. These results imply that enediynes such as NCS may be useful in ex vivo purging regimens and in in vivo treatment of microscopic residual disease in patients with neuroblastoma.
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PMID:Effects of neocarzinostatin upon the development of tumors from murine neuroblastoma cells. 798 86

Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LIL-2SN in order to examine the influence of localized interleukin (IL)-2 production on the immune response against a low major histocompatibility complex (MHC) class I, class II-negative, and intercellular adhesion molecule (ICAM)-1-negative tumor. Two neomycin-resistant (neo R) clones, N-2a/IL-2/L (2.5 +/- 0.4 U/ml/10(6) cells/24 h) and N-2a/IL-2/H (44.6 +/- 8.8 U/ml), were studied as representative low and high IL-2 producers, respectively. Using a recently developed retroperitoneal (r.p.) model for implantation of neuroblastoma in its natural site, we demonstrated that production of IL-2 by neuro-2a reduces its tumorigenicity in a dose-dependent fashion. T-cell, but not natural killer (NK) cell, depletion significantly increased tumor induced mortality in syngeneic A/J mice. Mice genetically devoid of T-cells (C.B-17 scid/scid) also experienced a significant increase in mortality rates. This indicates that the antitumor effect of locally secreted IL-2 is mediated primarily through activation of T-cells. Immunization of mice with irradiated N-2a/IL-2/H cells resulted in protection when challenged at a later date with unmodified neuro-2a cells. Depletion of CD8+, but not CD4+, T-cells prior to vaccination abrogated the protective effect, indicating that the priming phase of the immune response is CD8+ T-cell dependent. Mice with established r.p. tumors were vaccinated with N-2a/IL-2/H, which significantly prolonged their survival compared to unimmunized controls and to mice immunized with non-IL-2-producing neuro-2a cells. Because of the similarities of this model with the human tumor, our studies indicate that IL-2-transduced neuroblastoma cells may be effective in generating systemic immunity leading to eradication of minimal residual disease.
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PMID:Interleukin-2 gene transfer into murine neuroblastoma decreases tumorigenicity and enhances systemic immunity causing regression of preestablished retroperitoneal tumors. 813 49

Widely disseminated neuroblastoma in children older than infancy remains a very poor prognosis disease. Even the introduction of marrow ablative chemotherapy with autologous rescue has not significantly improved the outlook for these children, presumably because of a failure to eradicate minimal residual disease. One additional approach which may hold promise is the use of immunomodulation with cytokines such as IL2 in the setting of minimal residual disease (MDR), for example after intensive chemotherapy and ABMT. However, considerable variability in the susceptibility of neuroblastoma cells to natural killer (NK) and lymphokine-activated (LAK) killing has been observed, and it is presently unclear how NK and LAK cells recognise neuroblastoma cells. In this paper we examine expression of cell adhesion molecules on neuroblastoma to determine which of these modify interaction with NK and LAK cells. We find that LFA-3 (CD58), the ligand for CD2 is of predominant importance in predicting susceptibility of neuroblastoma to the cytotoxic actions of NK and LAK cells, while expression of ICAM-1 (CD54) may also modify susceptibility. These findings were confirmed by blocking experiments in which co-culture of target cells with ICAM-1 and LFA-3 reduced LAK and NK cytotoxicity. Study of the immunophenotypic features of each patient's neuroblastoma cells before induction of MRD may be valuable in determining the likely effect of IL2 in predicting disease reactivation.
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PMID:Mechanisms of selective killing of neuroblastoma cells by natural killer cells and lymphokine activated killer cells. Potential for residual disease eradication. 849 26

A case of hypervitaminosis A (HVA) as a complication of therapy for stage-IV neuroblastoma is presented. The patient was randomized to a trial of 13-cis -retinoic acid (a vitamin A-related compound) after completing routine chemotherapy. This acid was given as a means of maturing potential minimal residual disease. A routine follow-up bone scan revealed areas of increased activity, initially along the midshaft of the right ulna and subsequently bilaterally, which were ultimately found to be due to HVA. Hypervitaminosis A has not been previously reported in this setting, and awareness of the condition is important in centers where this treatment is contemplated.
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PMID:Hypervitaminosis A as a complication of treatment for neuroblastoma. 859 9


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