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)

Tumors of the mouse possess 2 isozymic forms of L-glycerol-3-phosphate dehydrogenase (alpha-GPDH) (EC 1.1.1.8) that can be distinguished from each other by their heat inactivation and electrophoretic properties. These isozymes share certain structural features, since dissociation and reassociation of mixtures of the 2 isozymes lead to the generation of a hybrid molecular species. This finding suggests that the structural genes for these isozymes are closely related. A number of spontaneous and transplantable tumors of the mouse have been analyzed in order to assess whether the pattern of embryonic and adult alpha-GPDH isozyme expression is correlated with the degree of tumor differentiation. The results indicate that no correlation between the type of isozyme expressed and the degree of tumor differentiation or growth rate was evident. A striking correlation exists, however, between the physical form of the tumor and isozyme expression; all solid tumors possess, predominantly, the adult isozymic form of L-glycerol-3-phosphate dehydrogenase, whereas all ascites tumors, including embryoid bodies from ovarian and testicular teratomas, possess the embryonic form. A solid tumor, the C1300 neuroblastoma, that initially possessed the adult isozyme, was cultured in vitro; this resulted in the disappearance of the adult isozyme and predominant expression of the embryonic isozyme. Reinjection of cultured neuroblastoma cells into a host mouse produced a solid tumor that possessed the adult isozyme. The exclusive presence of either adult alpha-GPDH in solid tumor growths or embryonic alpha-GPDH in ascites tumor growths after converting from one physical forms of the tumor to the other, strongly supports a genetic regulatory mechanism which depends on the reversible repression and activation of the structural loci for these isozymes.
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PMID:The reversible expression of an adult isozyme locus, Gdc-1, in tumors of the mouse. 95 97

Functionally active mammalian membrane-free ribosomes were prepared from rat forebrain, a solid tumor (mouse neuroblastoma C-1300) and a human tumor cell-line in suspension culture (HeLa). Proteins were extracted from these ribosomes and were resolved by a newly developed. Two dimensional gel electrophoretic procedure. Although the ribosomal protein patterns from the three preparations were generally similar, there were four obvious differences between the forebrain ribosomes and the ribosomes from the two neoplastic cell types.
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PMID:Comparison of ribosomal proteins from neoplastic and non-neoplastic cells. Resolution by two-dimensional gel electrophoresis. 112 27

Neuroblastoma is the most common solid tumor of children less than 5 years of age; yet the biology of this tumor is poorly understood. Neuroblastoma tumors are derived from neural crest precursors; they synthesize both adrenergic and peptidergic neurotransmitters. This study determined VIP receptor expression in primary neuroblastoma tumors prior to chemotherapy. The VIP receptor was expressed in 12 of 15 neuroblastoma tumors as determined by direct binding studies (KD = 1.3-12.4 nM) and VIP-mediated stimulation of adenylate cyclase. The VIP stimulation index for adenylate cyclase in the primary tumor was inversely correlated with the VIP content of the tumor, suggesting that VIP regulates its own receptor expression. Similar observations were made in vitro by comparison of two human neuroblastoma cell lines, IMR32 and SKNSH. Both cell lines were demonstrated to express specific, high affinity VIP receptors (KD = 4 nM and 2.5 nM for IMR32 and SKNSH, respectively). IMR32 cells contained very low levels of VIP (0.6 pg VIP/10(6) cells). Exogenous VIP stimulated adenylate cyclase 22-fold over basal activity and VIP inhibited proliferation of IMR32 cells by 49% in 6-day cultures. On the other hand, SKNSH cells synthesized high levels of VIP (6.3 pg/10(6) cells), metabolized VIP rapidly and demonstrated a low level of VIP-mediated stimulation of adenylate cyclase; their proliferation rate was minimally inhibited by exogenous VIP. These observations help validate the hypothesis that VIP serves as an autocrine growth factor in neuroblastoma.
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PMID:Vasoactive intestinal peptide: autocrine growth factor in neuroblastoma. 131 95

We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.
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PMID:Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity. 134 7

Neuroblastoma is the second most common solid tumor in infants and children. Improvement of therapy for stage IV patients remains the major goal of research in treatment of neuroblastoma. New approaches under study are focused in four main areas: (a) phase II studies; (b) mega-therapy procedures; (c) targeted therapy; and (d) immunotherapy. Future approaches will be closely linked to progress in laboratory investigation and more efficient use of currently available drugs. Of all the childhood malignancies, this is the one tumor where such an approach is most likely to be effective.
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PMID:Overview of current treatment of neuroblastoma. 138 90

From 1975 to 1986, 75 neonates were treated at the Institute Gustave-Roussy for a malignant solid tumor, comprising 1.7% of the overall oncopediatric population treated during the same period of time. Of these 75 patients, 47 (62%) presented with neuroblastomas, 15 (20%) with mesenchymal tumors, 9 (12%) with germ cell tumors and 4 with various other types of tumors. Treatment consisted of surgery in 63 patients, chemotherapy in 43 and radiotherapy in 18. The 5 year crude survival rate was 77%. Neuroblastomas did the best with a crude survival rate of 89%. The young age of the patients resulted in two types of problems: immediate tolerance and long term sequelae. The therapeutic regimen should take into account the good prognosis of the majority of these tumors in order to decrease delayed effects.
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PMID:[Neonatal malignant tumors. Apropos of 75 cases]. 161 Feb 75

Most studies of antibody-dependent cellular cytotoxicity (ADCC) by polymorphonuclear leukocytes (PMN) have supported oxidative lytic processes. This may be because the studies used nonhuman or nonneoplastic cells that were highly sensitive to reactive oxygen species or were small enough to be phagocytosed by PMN. We therefore investigated whether oxygen radicals participate in PMN cytotoxicity toward human neuroectodermal solid tumor cells sensitized by 3F8, which is an anti-ganglioside GD2 murine IgG3 monoclonal antibody with documented anticancer activity in humans. A 4-h 51Cr release assay was used to assess tumor cell lysis by hydrogen peroxide, superoxide, and hypochlorite. Nine of 11 GD2(+) human melanoma and neuroblastoma cell lines had equal or greater resistance to these oxidants as compared to a GD2(-) human carcinoma line (SKBr1-III) found by others (and confirmed by us) to be significantly more resistant to oxidative lysis than a murine cell line (P388D1) representative of those commonly used in cytotoxicity assays. To facilitate detection of oxidant-mediated lysis, subsequent studies of 3F8-mediated ADCC used GD2(+) targets that were relatively sensitive and others that were relatively resistant to oxygen radicals. Normal PMN and PMN obtained from children with chronic granulomatous disease, which do not generate reactive oxygen species, were equally effective in ADCC. Granulocyte-macrophage colony-stimulating factor, which primes oxidative responses of normal but not of chronic granulomatous disease PMN, enhanced ADCC by both kinds of PMN. During ADCC of 3F8-sensitized targets, with or without granulocyte-macrophage colony-stimulating factor, GD2(-) "innocent bystander" tumor cells (including P388D1) were not lysed, a finding consistent with unimportant extracellular release of cytotoxic mediators. Finally, antioxidant and antimyeloperoxidase moieties did not block ADCC. We conclude that oxidants are not key factors in 3F8-mediated lysis by PMN of human neuroectodermal tumor cells.
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PMID:Clinically effective monoclonal antibody 3F8 mediates nonoxidative lysis of human neuroectodermal tumor cells by polymorphonuclear leukocytes. 165 2

Neuroblastoma is the most common nonhematopoietic solid tumor of childhood and has been intensively studied for at least 4 decades. Despite this, few predictive histopathologic clues to its behavior exist. Age, anatomic sites of occurrence, and clinical stage have traditionally been the only reliable prognostic factors in this disease. A number of laboratory studies that focus on biologic features such as neurotransmitter synthesis (adrenergic and noradrenergic catecholamines), neurotransmitter enzyme expression (dopamine beta hydroxylase, choline acetyl transferase), cytogenetics (homogeneously staining regions, double minute chromosomes, chromosome 1p deletions), molecular genetics (N-myc oncogene amplification and expression), and immunophenotype (surface epitopes such as HLA antigens and GD2 ganglioside and intracytoplasmic determinants such as neurofilament protein, synaptophysin, chromogranin, and neuron specific enolase) now enable the pathologist to predict clinical course in many cases and to distinguish bona fide neuroblastomas, regardless of age, site, or histologic appearance, from a host of related but distinctly separate neuroectodermal tumor entities with apparent different histogenesis, treatment sensitivity, and prognosis.
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PMID:Neuroblastoma and other childhood neural tumors: a review. 169 Apr 16

Lag time (the interval between symptom onset and diagnosis) was described for 2665 children with lymphoma or a solid tumor who participated in Pediatric Oncology Group therapeutic protocols from 1982 until 1988. Median lag time ranged from 21 days for neuroblastoma to 72 days for Ewing sarcoma. Significant differences in lag time were found among diagnostic groups (p less than 0.001), even after adjustment for age, gender, and race. Age was significantly associated with lag time for all diagnoses (p less than 0.05) except Hodgkin disease. Girls had increased lag times for non-Hodgkin lymphoma (p = 0.02) but decreased lag times for Ewing sarcoma (p = 0.02). Differences in lag time related to race were significant only for children with osteosarcoma (p = 0.02), for which white children had longer lag times. Type of tumor and age were strongly associated with lag time. Within diagnostic groups, age, gender, and race failed to explain more than 16% of the variance in lag time, suggesting that other factors may play more prominent roles. Further study is necessary to identify these factors and to assess the relationship between lag time, stage of disease at diagnosis, and prognosis, especially before designing early-detection interventions for childhood cancer.
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PMID:Interval between symptom onset and diagnosis of pediatric solid tumors. 194 78

Magnetic resonance imaging (MRI) was performed in 126 children with malignant solid tumor between April 1984 and December 1990. The criteria of tumor visualization, localization, staging, prediction of kidney preserving and monitoring treatment were compared by MRI and CT for 47 children with neuroblastoma, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma and teratoma, MRI and CT were viewed together and an assessment was made as to whether the studies yielded equivalent information or whether one study was superior to the other. 1) The tumor were better visualized in 47% cases by MRI than CT. 2) MRI was superior to CT in 43% cases in evaluating the local spread of tumor. 3) There was little difference between MRI and CT in identification of lymph node metastases. 4) Without requiring the injection of intravenous contrast agents, MRI accurately defined displacement, invasion of renal vessels by neuroblastoma. MRI was excellent in prediction of kidney preserving. 5) MRI was useful to detect bone marrow metastases in neuroblastoma. The best imaging plane for a demonstration of bone marrow involvement was coronal in lower limbs.
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PMID:[The role of magnetic resonance imaging for treatment in children with malignant solid tumor]. 194 73


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