Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative study on the expression of the neural cell adhesion molecule (NCAM) in human neuroblastoma cell lines and tissues was undertaken. NCAMs are a family of closely related cell surface glycoproteins involved in cell-cell interactions. Using antibodies that recognise distinct epitopes on NCAM, their presence was shown in neuroblastoma, but these studies do not yield any information on the specific NCAM isoforms associated with the tumour. Western and Northern blot analyses were therefore carried out to characterise the NCAM isoforms in this neuroectodermal tumour. Western blot studies using the monoclonal antibody ERIC-1 showed that all human neuroblastoma cell lines tested expressed the 140 and 120 kilodalton isoforms of NCAM in their desialo state. Some of the cell lines also expressed NCAM-180. The data are corroborated by Northern blotting where a transcript of 7.4 kilobase pairs was identified only in lines expressing NCAM-180; the 6.7 and 5.4 kilobase pair transcripts coding for 140 and 120 kilodalton isoforms, respectively, were present in all the cell lines tested. The NCAM isoforms identified in neuroblastoma were also different from those found in adult and fetal brain tissue, suggesting that aberrations are expressed in the molecule during tumorigenesis.
 ...
PMID:Expression of neural cell adhesion molecule (NCAM) isoforms in neuroblastoma. 185 91

Increased dosage of cellular oncogenes resulting from amplification of DNA is a frequent genetic abnormality of tumor cells and the study of oncogene amplification has been paradigmatic for the usefulness of molecular genetic research in clinical oncology. Certain types of human tumors carry an amplified cellular oncogene at frequencies of up to 50-60%. Human neuroblastoma has been prototypic for the importance of oncogene amplification in tumorigenesis, and evidence is emerging that amplification may be an early event involved in a more malignant form of this cancer. It is unclear at which stage amplification plays a role in other cancers. Amplification of cellular oncogenes is a good predictor of clinical outcome in some human malignancies.
 ...
PMID:Amplification of cellular oncogenes: a predictor of clinical outcome in human cancer. 198 63

We detected a rearrangement in the N-myc gene region in a neuroblastoma from a 9-month-old girl. In this case, the N-myc gene was amplified 50-fold in the primary tumor, the lymph node metastasis, and the hepatic metastasis. The rearrangement was detected only in the primary tumor and the lymph node metastasis, whereas N-myc RNA and protein expression were detected only in the primary tumor and the hepatic metastasis. Both the rearranged N-myc gene and the normal N-myc gene were amplified 25-fold, and the rearrangement occurred 723 nucleotides downstream from the 3' end of exon 3. The cell line (NH-6) derived from the primary tumor showed N-myc gene amplification without this rearrangement. These results suggest the following: (a) the primary tumor had a least two clones; (b) the rearrangement interrupted N-myc gene expression; and (c) oncogenesis preceded N-myc gene amplification.
 ...
PMID:Neuroblastoma with DNA amplification and rearrangement in the N-myc gene region. 200 81

Increased dosage of cellular oncogenes resulting from amplification of DNA is a frequent genetic abnormality of tumor cells. Certain types of human tumors carry a specific amplified cellular oncogene at frequencies of up to 50 to 60%. Human neuroblastoma has been prototypic for a contribution of amplification to tumorigenesis, and evidence is emerging that amplification may be an early event involved in a malignant form of this cancer. It is unclear at which stage amplification plays a role in other cancers. Amplification of cellular oncogenes is a good predictor for clinical outcome in some human malignancies and is a paradigm for the application of oncogene research in a clinical context.
 ...
PMID:Oncogene amplification in neoplastic development and progression of human cancers. 209 49

Experience has shown that markers created in research laboratories can be adapted to everyday surgical pathology practice for malignant melanomas. These studies are feasible and readily conducted on frozen tissue as is routinely done in typing of lymphoma. The demonstration of heterogeneity using this monoclonal antibody panel, and other antibodies yet to come, may be important for prognostication. Tumor cell heterogeneity of surface antigens reflects disruption of the tumor cell's patterned gene expression. This should be regarded as an indication of different clones of cells (subsets) with a tumor, whether primary or secondary. It is entirely possible that autologous immune cells can kill or at least restrict the growth of subsets of melanoma cells having certain surface antigenic phenotypes while they are incompetent to handle other subsets. This would enable a particular phenotype within a primary melanoma to survive and escape the immunologic regression known to occur in 3 to 6 percent of these tumors. Such patients may present years later with metastases in the brain, liver, gastrointestinal (GI) tract, or lymph nodes. There are also implications in chemotherapy and chemoimmunotherapy for melanoma in this regard. It could be theorized that these agents may dispose of or restrict the growth of some phenotypes, leaving others in a resistant state. Perhaps the MDR gene is activated. Alternatively a tumor suppressor gene(s) could be absent or inactivated, as in neuroblastoma and carcinoma of the breast and lung. Markers present at the cell membrane surfaces and in the membranes themselves constitute an important field for study in the understanding of tumorigenesis. Many of these markers are present in embryos as early as the 4-to-8-cell stage and in blastocysts. Embryonic antigens in the intercell mass of blastocysts are stage-specific embryonic antigens. They are signals for organ development and the differentiation of cells. At various stages of this development, these markers disappear, especially upon differentiation into tissue types and specific organs. These cell signals are therefore organogenesis markers. Detecting a given antigen is not simple because it may be present but not immunohistochemically detectable because glycosylation, acetylation, phosphorylation, or sulfation have not taken place, or have resulted in a structural conformation not recognized by monoclonal antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Immunohistochemical phenotyping of malignant melanoma. A procedure whose time has come in pathology practice. 220 65

The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.
 ...
PMID:Differential expression of myc family genes during murine development. 241 62

Several studies have shown that neuroblastoma and retinoblastoma tumor cells often have elevated N-myc mRNA levels compared to normal adult neuronal or retinal tissues, and it has been suggested that increased expression of this protooncogene may play an important role in tumorigenesis or malignant progression in cells of neural origin. We have studied the effect of protein synthesis inhibitors on the N-myc mRNA levels in Y79 retinoblastoma and LA-N-5 neuroblastoma cells. We showed that when new RNA synthesis was inhibited by actinomycin D the levels of existing N-myc mRNA fell rapidly in both cell lines relative to total cytoplasmic RNA. The half-life for N-myc mRNA was approximately 30 min. Inhibition of protein synthesis by interfering with polypeptide elongation or by inhibiting initiation of protein synthesis increased the levels of N-myc mRNA at least 3-fold after 4 hours. Nuclear runoff transcription experiments showed that the protein synthesis inhibitors did not alter N-myc transcription rates. Combined actinomycin D treatment and treatment with protein synthesis inhibitors indicated that this increase in N-myc transcript levels was due to an increase in the N-myc mRNA lifetimes. Thus, N-myc transcript levels increased because they were more stable in protein synthesis-inhibited cells. Protein synthesis inhibition also increased c-myc mRNA levels in HL-60 human promyelocytic leukemia cells, but no increase was seen in the relatively low level of c-myc mRNA in protein synthesis-inhibited neuronal tumor cells. These results support the hypothesis that the regulation of N-myc in these neuronal and retinal tumor cells is similar to that of c-myc in other tumor types.
 ...
PMID:Regulation of N-myc transcript stability in human neuroblastoma and retinoblastoma cells. 244 70

At least 70% of human neuroblastomas display cytogenetically visible aberrations in the short arm of chromosome 1. We have used a panel of probes detecting polymorphic DNA loci, most of which were derived from a library of microdissected distal 1p chromosome fragments, to compare the hybridization pattern of DNA on nine different tumors and the corresponding normal tissue. In eight of the neuroblastomas allelic loss was observed with at least two probes. The deletions were of different size. Since a consensus deletion in all eight tumors included the segment 1p36.1-2, we conclude that genetic information related to neuroblastoma tumorigenesis is located within this approximately 10 megabase segment. Previous studies have revealed the amplification of MYCN in neuroblastomas. Our study did not provide evidence for a correlation between MYCN amplification and the 1p deletion, suggesting that the two genetic alterations result from molecular mechanisms that are not directly related to each other.
 ...
PMID:Neuroblastoma consensus deletion maps to 1p36.1-2. 248 56

We have evaluated the relationship between the neuronal myc gene (NMYC) and class I major histocompatibility complex (MHC) expression in human neuroblastoma (NB) tumor cell lines. Class I MHC surface Ag expression in NB cell lines varied from nearly undetectable to levels nearly as high as in a lymphoblastoid cell line. Class I MHC mRNA levels in NMYC-amplified NB cell lines were lower than levels observed in single copy NMYC NB cell lines. However, considerable variation in class I MHC surface Ag and mRNA expression was evident in NMYC-amplified cell lines. To determine directly whether NMYC might modulate class I MHC expression in NB, we transfected a plasmid containing a recombinant NMYC gene into two tumor cell lines derived from a NB and a related neuroepithelioma tumor. Constitutive overexpression of the recombinant NMYC gene produced no consistent change in class I MHC surface Ag or mRNA levels. To determine whether class I MHC expression might be developmentally regulated in adrenal medullary cells, the precursor cells of adrenal NB tumors, beta 2-microglobulin expression was measured in fetal and adult adrenal glands. beta 2-Microglobulin expression was not evident in the neuroblasts of a 24-wk-old fetal adrenal gland, whereas beta 2-microglobulin expression was present in the adult adrenal medulla. These data suggest that variation in class I MHC expression among NB cells may reflect the developmental stage at which neuroblasts were arrested during tumorigenesis.
 ...
PMID:Expression of class I histocompatibility antigens in neuroectodermal tumors is independent of the expression of a transfected neuroblastoma myc gene. 268 78

Endogenous opioid systems (endogenous opioids and their receptors) are known to participate in the regulation of tumor growth. The present study was conducted to examine whether [Met5]-enkephalin influences the growth of transplanted neuroblastoma, and to explore the role of other opioid peptides in carcinogenesis. A/Jax mice were inoculated with 10(6) S20Y cells and received daily injections of [Met5]-enkephalin. Dosages of 0.5 to 30 mg/kg delayed tumor appearance and prolonged survival of these mice; antitumor effects were blocked by concomitant injections of naloxone. Daily administration (10 mg/kg) of [Leu5]-enkephalin had no effect on neurotumor growth. [D-Ala2, D-Leu5]-enkephalin and ethylketocyclazocine, ligands selective for delta and kappa receptors, respectively, also did not influence neuro-oncogenesis. These results demonstrated the potent growth inhibiting effects of the naturally occurring opioid pentapeptide, [Met5]-enkephalin, and substantiate reports identifying and characterizing an opioid receptor (i.e., zeta) for which [Met5]-enkephalin is the most potent ligand.
 ...
PMID:Endogenous opioids and the growth regulation of a neural tumor. 284 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>