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)

To develop effective interleukin-2 (IL-2) protocols for pediatric malignancies, it is important to define IL-2 pharmacokinetics in children. In a phase I trial, we studied IL-2 pharmacokinetics in seven children, aged 6-18, five with leukemia, one with neuroblastoma, and one with rhabdomyosarcoma. IL-2 was administered as a 15-min i.v. infusion of either 1 X 10(6) CU/m2/dose or 3 X 10(6) CU/m2/dose (every Monday, Wednesday, and Friday for 3 weeks). IL-2 levels were determined using an IL-2-dependent murine T lymphocyte cell line bioassay. Peak IL-2 levels of 120-426 and 330-740 CU/ml were achieved after the lower and higher doses, respectively. Pediatric IL-2 kinetics resembled data reported for adults, fitting a two-compartment model (least-squares-regression technique), with an alpha half-life of 14.0 +/- 5.6 min (range, 6.3-23.1) and a beta half-life of 51.4 +/- 10.7 min (range, 33.0-66.0). The volume of distribution approximated total extracellular fluid (mean, 0.18 L/kg). Further clinical trials are needed to identify which pediatric malignancies are sensitive to immunotherapy and to establish the optimal treatment regimens.
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PMID:Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study. 225 63

Since May 1979, 47 patients with pediatric malignancy aged 1 to 18 years (median: 7) were treated with cryopreserved autologous bone marrow transplantation (ABMT) in the department of pediatrics, National Cancer Center Hospital. The malignancies were acute non-lymphocytic leukemia (n = 8), acute lymphocytic leukemia (n = 5), osteosarcoma (n = 7), neuroblastoma (n = 6), brain tumor (n = 5), rhabdomyosarcoma (n = 4), retinoblastoma (n = 3), Ewing's sarcoma (n = 3), non-Hodgkin's lymphoma (n = 2), malignant histiocytosis (n = 1), hepatoblastoma (n = 1), malignant melanoma (n = 1) and malignant neuroepithelioma (n = 1). Conditioning regimens for solid tumors were multi-agent high-dose chemotherapy, mainly consisted of cyclophosphamide (CY) 120 mg/kg or melphalan 180mg/m2 and that for hematological malignancies were CY with fractionated total body irradiation (12 Gy). In vitro purging by 4-hydroperoxycyclophosphamide was performed in 12 leukemia patients and 5 solid tumor patients. Of the 13 patients with acute leukemia, 1 died from relapse 1 year after the unpurged marrow transplantation and 1 relapsed in the testis. Remaining 11 patients are alive in continuous complete remission with a median follow up of 30 months (range, 2 to 65 months) after transplantation. The disease-free survival rate of them was 78%. Of the 34 patients with solid tumor, 21 patients died, their cause of death were relapse in 18 and each one of infection, graft failure and brain hemorrhage. Thirteen patients are alive without disease with a median follow up of 28 months (range, 2 to 107 months) posttransplant. The longest survivor is a brain tumor girl, and there are 5 other long survivors; 2 of them are osteosarcoma and each one of rhabdomyosarcoma, Ewing's sarcoma and malignant histiocytosis. The disease-free survival rate of total 34 solid tumor patients is 29%, but that of 17 patients who received ABMT in responsive and minimum tumor residue (MTR) period was 69%. These results suggest that autologous bone marrow transplantation is an effective and tolerable treatment for poor prognostic pediatric malignancies, especially for acute leukemia and such solid tumor as that in MTR state.
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PMID:[Autologous bone marrow transplantation in pediatric cancer]. 226 Aug 67

An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other cause unrelated to the tumour or its treatment, 44 (6%). Less than 10% of five year survivors of non-Hodgkin lymphomas, neuroblastoma, retinoblastoma, Wilms' tumour, or a soft tissue sarcoma died of recurrent tumour during the next 15 years, while more than 25% of five year survivors of Hodgkin's disease, ependymoma, medulloblastoma, and Ewing's tumour died of recurrent tumour during the corresponding period. Almost 50% of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years, a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given. Comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non-neoplastic causes. Five times the expected number of deaths from cardiovascular causes were observed, these were predominantly myocardial infarction and cerebrovascular accidents. There was no evidence of an excess in the number of suicides observed, but there were three times the expected number of deaths from accidents observed after central nervous system tumours. Two groups of patients were identified whose deaths were potentially avoidable. Seven patients with craniopharyngioma and panhypopituitarism presented with addisonian crises during periods of stress not adequately covered by exogenous corticosteroids. In the other group were children who received radiotherapy and later developed problems related to radiation fibrosis. We emphasize that our investigation relates to patients diagnosed with childhood cancer before 1971. The pattern of mortality that will emerge after recent treatment regimens, in which chemotherapy is being used more extensively, is likely to be different from that observed in our study.
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PMID:Late deaths after treatment for childhood cancer. 227 Sep 44

Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy.
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PMID:Acute mental status changes in children with systemic cancer. 230 89

As bone marrow transplantation is being used with increasing frequency, problems of storage space and cost, inventory control and disposal have arisen. Issues such as maximum storage time and acquisition of consent for marrow disposal need to be addressed before a large inventory is accumulated. Consideration should also be given to using non-infused marrows for research purposes. Eighty-three bone marrow transplant centers were surveyed in an attempt to establish a data base with regard to guidelines for storage of cryopreserved human bone marrow. Fifty-two centers (62.7%) responded to the questionnaire, 5 of which did not have an active cryopreservation program. The remaining 47 centers freeze and store autologous marrow from patients with leukemia, lymphoma, neuroblastoma and a large diversity of other conditions including solid tumors. Twelve centers (25.5%) specify maximum storage times of up to 5 years, but only 9 centers (19.1%) require the donor to sign a specific consent form for marrow disposal if it is not used for transplantation within a given time. Eighty-five percent of the responding centers reinfuse at least half of the marrows they freeze within 12 months of harvesting. It appears that at least 90% of marrows that are being reinfused have been stored for three years or less. However, the storage time of non-infused marrows extends even further, and autologous marrow has been reinfused successfully as long as eight years after storage.
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PMID:Cryopreservation and storage of human bone marrow: a survey of current practices. 230 98

Metastatic cord compression is a rare complication of malignant diseases in childhood. The most common causes are bone and soft tissue sarcomas, neuroblastoma, lymphoma and leukemia. The clinical manifestations, diagnosis, treatment and evolution of eight children with metastatic cord compression are presented. Diagnosis was based on computerized tomography that was pathological in all the cases, and confirmed by myelography in four patients. The cytological analysis of the cerebrospinal fluid was made in three patients being negative for tumoral cells in all of them. Treatment consisted on radiotherapy, chemotherapy and/or surgery depending on the tumor histology. Decompressive laminectomy was made in patients who did not show previous evidence of cancer. Functional prognosis was related with the degree of disablement at diagnosis and treatment.
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PMID:[Spinal cord compression in children with cancer]. 240 Jan 55

Normal human bone marrow cells were mixed with neuroblastoma cells from four different human cell lines, and the cell mixtures were separated by differential agglutination with soybean agglutinin (SBA). The unagglutinated cell fraction, previously shown to be highly enriched for the hematopoietic pluripotential stem cells and capable of reconstituting lethally irradiated adult patients with acute leukemia, was further fractionated by affinity chromatography on the lectin conjugated to Sepharose 6MB beads. Two independent assays, one using radiolabeling of the tumor cells and the other based on cloning of the neuroblastoma cells on agar, showed that the agglutination step alone removes 64-76% of the radiolabeled neuroblastoma cells and 85-98% of the clonogenic cells from the tumor/bone marrow cell mixture. Passage of the unagglutinated radiolabeled cells through SBA-Sepharose columns results in further purging of 28-53% of the neuroblastoma cells. Thus a combination of the two methods affords only one-log depletion for the neuroblastoma cells, compared to a three-log depletion achieved for a T-cell leukemia line CEM tested in parallel. It seems therefore that the agglutination technique, or the use of SBA-Sepharose columns, can be used only as a preliminary step for the purging of neuroblastoma cells from involved human bone marrow preparations. Staining with fluorescein isothiocyanate-conjugated SBA of nine different neuroblastoma cell lines, including the four tested in the fractionation studies, showed that more than 98% of the cells, of all the cell lines tested, specifically bind to the lectin, whereas no specific binding can be detected on the stem cell-enriched bone marrow cell fraction. However, the total number of receptors on the neuroblastoma cells is small compared to that of line CEM or normal granulocytes, which are strongly agglutinated by SBA. It seems therefore that the quantitative difference in the total number of SBA receptors is a crucial factor for purging by the agglutination technique or by affinity chromatography. Although these results show limitations to the use of both methods, this study establishes that all neuroblastoma cell lines tested express receptors for the lectin. Improved purging of neuroblastoma cells may possibly be achieved by targeting SBA-bound toxins or magnetic spheres to these receptors.
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PMID:Differential binding of soybean agglutinin to human neuroblastoma cell lines: potential application to autologous bone marrow transplantation. 241 94

Therapeutic efficacy and toxicity were evaluated in 28 children with acute lymphoblastic leukemia, in ten with acute nonlymphoblastic leukemia (ANLL), and in 13 with metastatic neuroblastoma. All were refractory to standard chemotherapeutic agents and 25 were refractory to an investigational drug. The initial dose was 12 mg/m2/day and was based on an established maximal dose tolerated in adults. This dose was found to be intolerable in 5 of 5 children with leukemia. Similarly an initial dose of 9 mg/m2/day was intolerable in 4 of 5 patients with leukemia. The starting dose in the next 28 children with leukemia or neuroblastoma was 3 mg/m2. This drug was gradually increased to the highest tolerated dose by 3-mg/m2 increments. Fifteen children with acute lymphoblastic leukemia, 3 children with ANLL, and 2 children with neuroblastoma received the drug daily. Seven patients with ANLL and 7 patients with neuroblastoma received the drug biweekly. Seventeen patients with acute lymphoblastic leukemia, 6 patients with ANLL, and 5 patients with neuroblastoma had an adequate trial of the drug. An adequate trial was defined as a minimum of 5 weeks of therapy unless progressive disease developed. Side effects of the drug were striking and included fever, hypotension, myalgia, bone pain, arthralgia, arthritis, abdominal pain, liver toxicity, thrombocytopenia, and neurotoxicity. No complete remission occurred although interferon levels above 100 units/ml were induced in nearly 50% of the patients.
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PMID:Phase II trial of a complex polyriboinosinic-polyribocytidylic acid with poly-L-lysine and carboxymethyl cellulose in the treatment of children with acute leukemia and neuroblastoma: a report from the Children's Cancer Study Group. 241 2

A Phase II study of poly(I,C)-LC was performed in 28 children and adolescents with acute lymphoblastic leukemia (ALL), 10 with acute nonlymphoblastic leukemia (ANLL), and 13 with metastatic neuroblastoma. All were refractory to standard chemotherapeutic agents and 25 to an investigational drug. Initial doses of 12 mg/m2 and 9 mg/m2 were intolerable. However, 9 mg/m2 was tolerable in the majority of patients when the drug was started at 3 mg/m2 and increased by 3 mg/m2 increments. Fifteen children with ALL, three with ANLL, and two with neuroblastoma received the drug daily. Seven patients with ANLL and seven children with neuroblastoma received the drug biweekly. Twenty-eight patients received an adequate trial, which was defined as a minimum of 5 weeks at the maximal tolerated dose, unless there was progressive disease at the maximal tolerated dose. Side effects of the drug were striking, and included fever, hypotension, myalgia, bone pain, arthralgia, arthritis, abdominal pain, liver toxicity, thrombocytopenia, and neurotoxicity. No complete remissions occurred in spite of interferon levels above 100 U in nearly 50% of patients.
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PMID:Phase II trial of poly(I,C)-LC, an interferon inducer, in the treatment of children with acute leukemia and neuroblastoma: a report from the Children's Cancer Study Group. 241 84

The validity of permeabilized cells as a model of DNA and RNA synthesis was studied with the use of mouse S-49 lymphoblastoma cells rendered permeable by exposure to L-alpha-lysophosphatidylcholine. The permeabilized cells readily incorporated exogenously supplied cytosine and uracil nucleotides into HClO4-insoluble macromolecular material. However, the incorporation of these tracers did not require the three other complementary nucleotides, and adenine, guanine or thymine nucleotide tracers were incorporated at much lower rates. These results, which were also obtained with permeabilized Abelsohn-leukaemia-virus-transformed mouse macrophages, mouse neuroblastoma cells and S-49 lymphoblastoma homogenates, are inconsistent with semi-conservative DNA replication or RNA transcription; rather, they suggest the involvement of terminal nucleotidyltransferase(s) that mediate the incorporation of uracil and cytosine nucleotides. DNA synthesis was restored when permeabilized cells or cellular homogenates were supplemented with denatured salmon testes DNA. These results suggest that endogenous cellular DNA is impaired in its function as a template for DNA replication and transcription in vitro. Metabolic channelling or compartmentation of nucleic-acid-precursor pathways could not be demonstrated in the permeabilized cells.
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PMID:Incorporation of nucleotide tracers into nucleic acids in permeabilized cells and cellular homogenates. 243 80


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