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)

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.
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PMID:Endogenous opioids and the growth regulation of a neural tumor. 284 18

In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do not transform normal cells in culture. In experimental models cooperation between two oncogenes can induce transformation of early passage cells, and this has become the basis of an hypothesis for multistep carcinogenesis. Proto-oncogene products also show sequence homology to various components in the mitogenic pathway (growth factors, growth factor receptors, signal transducing proteins and nuclear proteins), and it has been postulated that they may cause deregulation of the various components of this pathway. In human tumours single or multiple oncogene activation occurs. The pattern of oncogene activation in common solid malignancies is not consistent within any one class of tumour, nor is it uniform between classes, with three exceptions. In neuroblastoma, breast cancer, and perhaps in lung cancer there is relatively consistent activation of N-myc, neu, and c-myc/N-myc, respectively. Amplification of these genes generally correlates with poor prognosis. The introduction of methods for the direct study of oncogene transcription and their products will undoubtedly broaden our vision of cancer biology in man and, hopefully, add diagnostic and prognostic precision to tumour typing.
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PMID:Cellular oncogenes in neoplasia. 331 99

This monograph has emphasized the molecular aspects of both the differences between cancer and normal cells and the development of a cancer cell from a normal cell. Multistage carcinogenesis is now well known in a variety of histogenetic circumstances, and definable stages of initiation, promotion, and progression have been identified. Activation of proto-oncogenes in neoplasms may occur at any time during the development of malignancy, but most examples to date have shown this occurrence during the final stage of progression. A new form of carcinogenesis, that induced by specific genetic constructions in vivo or in vitro, has been accomplished. The specificity of genetic carcinogenesis can reside in the specific construct itself, especially in tissue-specific enhancer regions. On the other hand, the specific molecular genetic characteristics of at least one human genetic condition resulting in a high incidence of a specific histogenetic type of neoplasia, hereditary neuroblastoma, have been partially characterized. All of the various types ov carcinogenesis--genetic, viral, chemical, and radiation--exhibit, or at one time or another or in one situation or another, multiple stage ion their development.
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PMID:The molecular determinants of carcinogenesis. 342 69

Ependymoblastoma developed in a 28-month-old girl whose epileptic mother took diphenylhydantoin and methylphenobarbitone throughout pregnancy. The child was also shown to be a genetic carrier for ornithine transcarbamylase deficiency, an x-linked inborn error of urea cycle metabolism. The possibility of transplacental carcinogenesis should be considered, as other juvenile embryonic tumors such as neuroblastoma, melanotic neuroectodermal tumor, and mesenchymoma have been reported in offspring after diphenylhydantoin use by the mother during pregnancy.
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PMID:Ependymoblastoma associated with prenatal exposure to diphenylhydantoin and methylphenobarbitone. 397 71

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.
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PMID:Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. 648 68

A series of N-alkyl-N-nitrosoureas, which produce both alkylation and carbamoylation, was found to induce neurite formation in mouse neuroblastoma N-18 cells just as does N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Related compounds, which produce only carbamoylation or nitroguanidination, did not induce morphological differentiation, while methyl methanesulfonate (MMS) and dimethyl sulfate, which produce only alkylation, did. MNNG, methyl nitrosourea and MMS were more effective in the induction of differentiation than their corresponding ethyl derivatives. These data suggested that alkylation contributed to the induction of morphological differentiation in N-18 cells.
Carcinogenesis 1982
PMID:Induction of morphological differentiation in cultured mouse neuroblastoma cells by alkylating agents. 715 Dec 51

Gene amplification is a model of proto-oncogene alterations occasionally observed in human tumors. This amplification can, in some cases, have prognostic value (N-myc in neuroblastoma, c-erbB2 and int-2 in breast cancer, etc.). Amplifications of the proto-oncogenes c-myc, c-erbB2 and int-2 have not yet been report in prostate adenocarcinoma, which, like breast cancer, is hormone dependent. We sought amplifications of these three proto-oncogenes by means of Southern blotting in 15 human prostate adenocarcinoma specimens, most of which were advanced (7 stage C and 6 stage D1 or D2). We confirmed the lack of c-myc and c-erbB2 amplification, regardless of the stage, in contrast to the case of breast cancer. Int-2 amplification was observed in one advanced tumor with bone metastases, out of a total of six stage D tumors. The precise frequency of int-2 amplification and its role in prostate carcinogenesis remain to be determined.
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PMID:Gene amplifications in advanced-stage human prostate cancer. 774 Jun 53

There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c-myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and over-expression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma.
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PMID:Down-regulation of c-myc oncogene during NGF-induced differentiation of neuroblastoma cell lines. 786 34

3'-methyl-3-hydroxy-chalcone (3'Me-3-C), a derivative of chalcone, inhibited the proliferation of various kinds of human malignant tumor cells, such as HGC-27 (gastric cancer), HeLa (cervical carcinoma), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow-cytometric analysis of HGC-27 cells revealed that 3'Me-3-C perturbed the cell cycle, i.e., it delayed passage through the S phase, and/or caused arrest in the G0/G1 phase. 3'Me-3-C inhibited the binding of [6,7-3H]estradiol to type-II estrogen-binding sites dose-dependently, and altered the pattern of protein synthesis and phosphorylation, which may explain 3'Me-3-C-induced inhibition of cell proliferation. In addition, 3'Me-3-C also suppressed the promoting activity of 12-0-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.
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PMID:Inhibitory effects of 3'-methyl-3-hydroxy-chalcone on proliferation of human malignant tumor cells and on skin carcinogenesis. 837 34

Autocrine stimulation of the type I insulin-like growth factor receptor (IGF-IR) by IGF-II is one mechanism that allows cancer cells to maintain unregulated growth and to resist programmed cell death (PCD). SH-SY5Y and SHEP cells are cloned human neuroblastoma (NBL) lines originating from a single primary tumor. SH-SY5Y cells, which express abundant cell surface IGF-IR and produce IGF-II, exhibit serum independent growth and resist PCD due to hypoxia and hyperosmolar conditions. In contrast, SHEP cells, which produce no IGF-II and express five-fold fewer IGF-IRs, die in serum-free media or following exposure to metabolic stressors. To better understand the roles of IGF-IR and its ligand, IGF-II, in NBL carcinogenesis, we stably transfected SHEP cells with either IGF-II or IGF-IR. Unregulated expression of IGF-II did not alter the growth characteristics of SHEP/human IGF-II transfectants. In contrast, overexpression of IGF-IR allowed SHEP/IGF-IR transfectants to survive in media supplemented only by IGF-II. IGF-IR abundance correlated in a graded fashion with resistance to PCD in response to three different death-inducing paradigms: mitogen withdrawal, hyperosmolar metabolic stress, and treatment with etoposide. Our results suggest that adjuvant therapy aimed at reducing IGF-IR abundance may enhance chemotherapy-coupled apoptosis in the treatment of NBL.
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PMID:Insulin-like growth factor I receptor prevents apoptosis and enhances neuroblastoma tumorigenesis. 881 51


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