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)

Supranormal temperatures inhibit selectively the growth of malignant cells more than that of normal cells. The autoradiographic determination of the 3H-thymidine-labelling-index (LI) in vitro is a suitable method for the examination of thermosensitivity of individual human tumours. 44 solid tumours of children (Wilms' tumours, neuroblastomas, osteogenic sarcomas, non-Hodgkin-Lymphomas and other tumours) were studied by the temperatures 37.5 and 42.5 degrees C/120 min, with this method. 90% of the histologically undifferentiated tumours showed a highly significant inhibition of the 3H-thymidine incorporation between 28.6 and 79.9% with an average of 51.1%. In 4 histologically mature tumours (carcinoma of the adrenal cortex, malignant hepatoblastoma, fibrosarcoma, hamartoblastoma) no significant decrease of the LI was present. The inhibition of incorporation with hyperthermia cannot be correlated with the primary magnitude of the LI with normothermia. In 1 neuroblastoma a 75% rise of the LI was found possibly due to exogenic caused thermotolerance. The individuality of the reaction towards heat may contribute to the biological characterization of tumours.
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PMID:The effect of hyperthermia 42.5 degrees C on the incorporation of 3H-thymidine into the DNA of solid tumours in childhood. 51 52

Murine monoclonal antibody (MAb) 3F8 was previously shown to react with disialoganglioside GD2, but not with GD3, GT1b, GD1b, GD1a, GM1, GM3 and GM4. However, when the base-treatment step was ommitted from the standard neuroblastoma ganglioside extraction procedure, immuno-thin-layer-chromatography (ITLC) using 3F8 and other anti-GD2 MAbs revealed a new ganglioside band, abbreviated as NG (Rf 0.342) besides GD2 (R 0.183). It migrated below GD3 (Rf 0.358) on high-performance (HP) TLC plate and its binding to 3F8 on ITLC could be inhibited by rat anti-3F8 idiotypic antibody Idio-2, while the binding of GD2 to MAb 3F8 was not affected. Immunochemical analysis showed that this new neuroblastoma ganglioside contained alkali-sensitive O-acetylated sialic-acid residues recognized by MAb DI.I. After base treatment, its subsequent identity on ITLC was confirmed to be GD2. Lactonization of GD2 yielded 2 major bands, with Rf values (0.401, 0.583) distinct from that of the new ganglioside band. In addition, MAb DI.I did not bind to any of these GD2 lactones. Of 15 anti-GD2 MAbs studied, 13 reacted strongly with the novel ganglioside NG. By ITLC, this NG was found in ganglioside extracts of fresh surgical tumor specimens (4/4 neuroblastomas, I/I schwannoma and I/I anaplastic astrocytoma), and nude mice/rat xenografts (2/2 neuroblastomas, 2/2 osteogenic sarcomas). These data provided the first evidence that O-acetylated GD2 is a naturally occurring ganglioside derivative in human tumors and that it could cross-react with most anti-GD2 antibodies.
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PMID:A novel O-acetylated ganglioside detected by anti-GD2 monoclonal antibodies. 173 May 13

Retinoblastoma (RB) tumours form in the eyes of young children when homozygosity for a mutation at the Rb-1 locus develops in a somatic retinal cell. A similar shift to homozygosity for the RB mutation has been observed in osteogenic sarcoma (OS) tumours that commonly arise as second tumours in children who survive RB. This observation suggests that the Rb-1 locus controls the expression of genes with oncogenic potential; a possible target is the oncogene N-myc, which is sometimes amplified and over-expressed in the neuroectodermal tumours neuroblastoma and RB. However, N-myc is developmentally regulated in normal murine embryogenesis, and an alternative possibility is that the expression of the gene in tumour cells reflects their embryonic origin and is unrelated to the RB mutation. We have therefore examined N-myc expression in various fetal, adult and tumour tissues, and report here that the gene is expressed in fetal but not in adult brain and retina and in near-diploid RB tumour samples at levels similar to those observed in normal fetal retina. Only RB tumours with genomic amplification of the N-myc gene exhibited increased levels of expression; and no N-myc transcripts were detected in osteogenic sarcomas initiated by mutations at the Rb-1 locus. We therefore conclude that the expression of N-myc in RB tumours probably reflects the origin of the tumour from an embryonic tissue normally expressing the gene and is not directly associated with the mutation at the RB locus.
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PMID:Tumour induction by the retinoblastoma mutation is independent of N-myc expression. 242 1

Rhabdomyosarcoma (RMS), a common soft tissue tumor in children, may often be difficult to distinguish from Ewing's sarcoma, neuroblastoma, and malignant lymphomas. Confirmation of the skeletal muscle origin of RMS depends partly on the demonstration of striations in tumor cells that are usually undetectable in poorly differentiated tumors. A number of tissue markers (e.g., myoglobin and desmin) are currently being used to establish the origin of RMS. However, most of these markers lack specificity and have relatively low sensitivity. We have investigated the specificity and sensitivity of anti-skeletal muscle antibody (ASMA) from patients with myasthenia gravis in the diagnosis of childhood RMS. Out of eight cases of childhood RMS (four embryonal and four alveolar) examined, two showed striations with hematoxylin and eosin and four with phosphotungstic acid hematoxylin. Myoglobin was detected in five tumors; only well-differentiated tumor cells contained myoglobin. Anti-desmin antibody and ASMA reacted with cells in all the eight tumors whether or not the tumor cells were well differentiated. Anti-skeletal muscle antibody did not react with nine lymphomas, four Ewing's sarcomas, four neuroblastomas, four osteogenic sarcomas, four lipomas, eight duct carcinomas of the breast, and eight squamous cell carcinomas of the lung. Eight leiomyomas and four leiomyosarcomas of the uterus were compared for their reactivity with anti-desmin antibody and ASMA. All the tumors stained with anti-desmin antibody and none with ASMA. The results show that ASMA is useful in the diagnosis of childhood RMS and is a more sensitive reagent than anti-myoglobin antibody. Unlike anti-desmin antibody, it can distinguish skeletal muscle tumors from smooth muscle tumors.
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PMID:Use of anti-skeletal muscle antibody from myasthenic patients in the diagnosis of childhood rhabdomyosarcomas. 355 41

Using auto-radiographic techniques in vitro studies performed to analyse the growth rate in 13 cases of neuroblastoma, 6 recurrent tumours (assorted) and 7 metastatic tumours. The cell kinetic parameters using 3H thymidine markers, DNS synthesis, mitotic rate and mean cycle rate were investigated. The growth rate can only be calculated approximately. The results show that neuroblastomas grow incredibly fast. The cell-cycle period varies between 13.1 and 266.3 hours and averages 71 hours. Recurrent tumours have a tendency to have the same growth rate as the primary tumour. Primary metastases of Wilm's tumours and osteogenic sarcomas proliferate rapidly with a cell-cycle of 13.0- 87.0 hours (average 37.7 hours). All tumours have a distinctly individual proliferation pattern. Cell division and growth rate of malignant tumours are important in relation to radiotherapy and the use of cytotoxic drugs. These factors are expressed as a "cell-kinetic therapeutic index", which helps to predict the effectiveness of cytotoxic drugs and radiotherapy. Two cases of neuroblastoma were classified as resistant. Most tumours excluding the fibrosarcomas react well against two cytotoxic reagents. The cell-kinetic pattern and the sensitivity results are used in determining the treatment of recurrences and metastases. The relationship of these investigations in clinical practice is discussed.
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PMID:[The role of cell proliferation kinetics and cytostatica - test for sensitivity of neuroblastomas, recurrent tumours and tumour metastases (author's transl)]. 728 79

More aggressiveness in treatment of childhood malignancies has had an evident impact on survival and rate of cure but, it has also allowed us to discover long-term effects of these treatments, and second malignant tumors of them. Between 1970 and 1993, 472 cases of malignant tumors in childhood were diagnosed in our department. Six of them (1.27%) developed a second tumor (five malignant and one benign). Relationship between first and second tumors are: seven years old boy, cervical lymphosarcoma-thyroid carcinoma; eleven years old boy, osteogenic sarcoma-vesical carcinoma: two years and six months old boy, cerebellar astrocytoma-soft tissue osteogenic sarcoma; five years old girl. Wilm's tumor-scapular osteogenic chondroma; one year and a half old girl, abdominal neuroblastoma-granulocytic sarcoma (chloroma); twelve years old boy. Hodgkin's disease-acute myeloblastic leukemia. All of them were clearly related to concogenic effect of radiation or chemotherapy.
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PMID:[Second tumors in childhood]. 776 70

Gestational exposure to ethanol causes defects in neuronal migration, fasciculation, and synaptogenesis, developmental events that depend on the patterned expression and function of cell adhesion molecules (CAMs). Recombinant human osteogenic protein-1 (hOP-1) increases cell-cell adhesion and promotes cell clustering in proliferating neuroblastoma x glioma hybrid NG108-15 cells by strongly inducing N-CAM and L1. Here we show that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N-CAM. This inhibition was reproduced by other alcohols in proportion to their chain length, but not by teratogenic anticonvulsants or phenylalanine. Ethanol inhibition of hOP-1 morphogenesis was inversely proportional to the concentration of hOP-1 and, hence, to the levels of N-CAM and L1. Low concentrations of ethanol (IC50 5-10 mM) inhibited cell-cell adhesion in hOP-1-treated cells, and this action too was reproduced more potently by propanol and butanol. Ethanol may perturb brain and skeletal development by inhibiting CAM-mediated cell-cell interactions.
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PMID:Ethanol inhibits neural cell-cell adhesion. 813 68

Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
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PMID:Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells. 822 84

The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
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PMID:Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins. 827 80

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool.
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PMID:[Ewing sarcoma. Diagnostic imaging]. 970 Jul 72


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