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)

Thirteen children with localized (Evans stage I or II) thoracic primary neuroblastoma were divided into two groups according to the type of therapy administered, in order to compare the therapeutic efficacy and morbidity of excisional surgery followed by either irradiation alone or irradiation plus chemotherapy (group A) with similar surgery alone (group B). Group A consisted of 6 children (mean age 1 year, 2 months). Complete surgical excision was accomplished in 2 patients, while 4 had microscopic residual. All 6 patients are free of disease at 26--76 months (mean 47 months), including 2 who had recurrent tumor and received additional therapy. Two have developed congestive heart failure and one severe scoliosis secondary to irradiation. Of the 7 children in group B (mean age 2 years, 2 months), 3 had microscopic residual tumor and 2 had adjacent lymph node involvement. After 12--47 months (mean 23 months), no recurrence or surgery-related morbidity has been observed. From these limited data it appears that surgery alone may provide adequate therapy for localized thoracic neuroblastoma and obviate the morbidity associated with multimodal therapy.
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PMID:Management of localized thoracic neuroblastoma. 50 72

Disseminated neuroblastoma is a malignancy of children often treated by intensive chemotherapy/radiotherapy followed by autologous bone marrow transplantation (ABMT). A high proportion of those treated subsequently relapse. It is unknown if relapse is a consequence of residual disease in the patient or of contaminating malignant cells remaining in the infused marrow, which, of necessity, is harvested and stored prior to ablative chemotherapy/radiotherapy. The assumption that residual cells in the infused marrow contribute to relapse has lead to the adoption of marrow purging prior to reinfusion. However, neither the necessity nor the efficacy of the procedure have been established. We now show how retroviral-mediated gene transfer using the LNL6 vector may resolve this issue. Clonogenic neuroblastoma cells in patient marrow can be transduced and the NEOR gene detected by observing individual neuroblastoma cell colony growth in G418, and by polymerase chain reaction (PCR) of individual colonies. Efficiency of transduction is between 0 and 13.5%. If marrow is exposed to LNL6 prior to infusion and marked cells are detected at the time of relapse, this would demonstrate that infused marrow contributed to disease recurrence. The technique could then be used to analyze the efficacy of marrow purging techniques. Since normal progenitor cells from these patients are also marked, the technique can be used to study factors that modify reconstitution and transducibility of infused marrow. Clinical studies using this approach have now begun.
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PMID:Retrovirus-mediated gene transfer as an approach to analyze neuroblastoma relapse after autologous bone marrow transplantation. 139 Oct 32

Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method.
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PMID:High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. 190 68

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.
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PMID:Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. 194 Oct 67

From 1982 to 1987, 40 children with non-metastatic thoracic neuroblastoma were treated with the same therapeutic regimen. According to TNM staging, there were 11 CS I, 19 CS II, and 10 CS III. All patients underwent surgery; 30 had primary surgical excision; in 10 whose tumors were deemed unresectable, surgery was delayed until after a trial of chemotherapy. Operation was completed by several courses of chemotherapy in case of microscopic residual disease or regional lymph node involvement; radiotherapy was delivered in case of gross residual disease. Using this therapeutic approach, EFS is 92% with a median follow-up of 40 months. Severe complications were rare and sequellae appear to be related to the disease, i.e., neurologic consequences of cord compression.
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PMID:Nonmetastatic thoracic neuroblastomas: a review of 40 cases. 205 69

From 1982 to 1987, forty children with non-metastatic thoracic neuroblastoma were treated with a same therapeutic regimen. According to TNM staging, there were II CS I, 19 CS II and 10 CS III. All patients underwent surgery; thirty had primary surgical excision; in ten whose tumor were deemed uresectable, surgery was delayed until after a trial of chemotherapy. Operation was completed by several courses of chemotherapy in case of microscomic residual disease or lymph node involvement; radiotherapy was delivered in case of gross residual disease. Using this therapeutic approach. Event Free Survival is 92% with a median follow up of 40 months. Severe complications were rare and sequellae appear to be related to the disease i.e. neurologic consequence of cord compression.
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PMID:[Localized thoracic neuroblastoma: the role of surgery and therapeutic results. Apropos of 40 cases]. 208 61

Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.
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PMID:Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study. 215 66

We describe an in vitro method which is useful for purging autologous bone marrow of neuroblastoma cells. The method utilizes a single murine monoclonal antibody 3G6 (an immunoglobulin MK) which we have previously developed against the ganglioside GD2; undiluted human complement; and unfractionated whole bone marrow at 1 X 10(7) nucleated cells/ml. Tumor cell clonogenic assays, Hoechst 33342 fluorescent nuclear stain, and trypan blue viability stain methods were used to assay cytotoxicity. This complement-mediated cytotoxicity technique killed 99.9-100% of neuroblastoma cell lines NMB-7, LAN-1, LAN-5, and IMR-6, while normal marrow precursor cells were not detectably damaged. The presence of normal bone marrow did not inhibit the human complement-mediated cytotoxicity. Applying the cytotoxicity method to whole unseparated bone marrow demonstrated killing of seeded neuroblastoma cells, with no gross hemolysis or cell clumping. The method did not require expensive special equipment, use of animal complement sera, or prior fractionation of the bone marrow. The average marrow nucleated cell recovery was 95%. These studies indicate that in vitro purging of autologous marrow infiltrated with neuroblastoma with monoclonal antibody 3G6 and human complement is both technically feasible and effective in eradicating residual tumor while preserving bone marrow stem cells.
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PMID:Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow. 241 4

Treatment of neuroblastoma in children consists of primary excision with adjuvant radiation and chemotherapy. When the tumor invades surrounding structures that cannot be safely excised or when distant metastasis is present, the patient has a poor prognosis. Because the CO2 laser can be used to excise malignant tumors without seeding the surrounding tissue and because the defocused beam can vaporize malignant cells, we compared partial scalpel excision and partial laser excision of C1300 murine neuroblastoma to the growth rate of residual tumor. In 25 mice, 75% of the tumor was excised with a scalpel, and in another 25, the same percentage was excised with the CO2 laser (10 W). CO2 laser excision significantly decreases the growth of residual neuroblastoma (P less than .01). However, the effect appears to be a function of increased tumor immunogenicity after laser excision rather than the increased tumor kill. We conclude that CO2 laser excision of neuroblastoma may prove to be superior to scalpel excision for primary surgical treatment of neuroblastoma.
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PMID:Beneficial effects following carbon dioxide laser excision on experimental neuroblastoma. 249 3

As neuroblastoma, the most common solid tumour in childhood, may contain all the constituents of the catecholamine biosynthesis cascade, some of these constituents may be produced in excess in a varying mixture reflecting the wide variability in expression of differentiated features of the tumour. We have measured plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA) and 3,4-dihydroxyphenylalanine (DOPA), and plasma activities of dopamine beta-hydroxylase (DBH) and aromatic L-amino acid decarboxylase (ALAAD) in 18 patients with neuroblastoma, in 13 at various times during the course of their disease. Activities of serum lactic dehydrogenase (LDH), serum levels of ferritin (FER) and neuron-specific enolase (NSE), and urinary vanilmandelic acid (VMA) were also determined. NE, E and DBH were found not to reflect tumour activity. In untreated active neuroblastoma DOPA or ALAAD (10 out of 10) or both (six out of 10) were clearly elevated. In all 13 patients where samples were obtained during chemotherapy, ALAAD activities fell within the normal range, while DOPA decreased more slowly. During relapse, DOPA and, especially, ALAAD, rapidly increased; in all six patients who had a relapse both DOPA and ALAAD were elevated. In complete remission (eight patients), ALAAD was normal in all patients, but DOPA remained elevated in the one patient who later experienced a relapse. Our preliminary conclusion is that combined measurements of plasma ALAAD and DOPA may be useful markers for neuroblastoma activity at diagnosis, but even more so in indicating residual disease (DOPA) and in the early detection of relapse (ALAAD).
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PMID:Combined measurements of plasma aromatic L-amino acid decarboxylase and DOPA as tumour markers in diagnosis and follow-up of neuroblastoma. 250 83


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