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)

Five children with neural crest tumors (two ganglioneuromas, one ganglioneuroblastoma, and two neuroblastomas) were investigated regarding neuropeptide Y-like immunoreactivity (NPY-LI) in tumor tissue and plasma at diagnosis and during surgery. Radioimmunoassay of extracted plasma revealed higher NPY-LI at diagnosis of neuroblastoma (640 and 230 pmol/L resp) than ganglioneuroblastoma or ganglioneuroma (74, 45, and 26 pmol/L resp). During surgery of neuroblastoma plasma NPY-LI increased two- to four-fold while no peroperative increase was seen in the other children. NPY-LI was considerably higher in neuroblastoma tissue (220 pmol/g and 144 pmol/g) than in ganglioneuroblastoma (40.2 pmol/g), ganglioneuroma (0.6 and 4.4 pmol/g), or healthy adrenal tissue (5.5 pmol/g). The highest NPY-LI concentration was found in neuroblastoma metastasis, 3,091 pmol/g. Gel-permeation chromatography of a neuroblastoma tumor showed that a majority of NPY-LI was representing intact NPY (NPY 1-36) while metastasis and plasma from the same child mainly contained smaller immunoreactive fragments. High concentrations of systemic NPY in neuroblastoma patients are of tumoral origin. Plasma levels of NPY and its fragments can be useful in diagnosing and monitoring neuroblastoma, and for early detection of relapse or metastatic disease. A possible involvement of NPY in neuroblastoma tumor growth and spread deserves further investigation.
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PMID:Neuropeptide Y in neuroblastoma: increased concentration in metastasis, release during surgery, and characterization of plasma and tumor extracts. 849 45

A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancement of tumor growth in several rodent models of malignancy. One common action, the inhibition of histamine binding to and catalytic activity of cytochrome P450 monooxygenases, is highly correlated with potency to enhance tumor growth. Among members of this drug ensemble, the antiestrogen tamoxifen has been shown in controlled clinical studies to increase the incidence of uterine and gastrointestinal cancer and to accelerate the course of gastric cancer, and the tamoxifen analogue clomiphene has been linked to neuroblastoma and the tricyclic group of antidepressants to ovarian cancer. The determination of drug affinities for protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemicals that impart oncologic risks to humans.
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PMID:Enhancement of tumor growth by drugs with some common molecular actions. 864 28

Neuroblastoma is the most common extracranial tumor in children, and cytogenetically, chromosome 1p deletions, extrachromosomal double minutes, and homogeneously staining regions (HSRs) are commonly observed in cell lines and in tumors in advanced stages. It is found that an HSR represents genomic amplification of N-myc, which plays a key role in determining the aggressiveness of neuroblastoma. However, stage IV neuroblastomas or cell lines which lack N-myc amplification are also progressive, and some of them show evidence of N-myc expression in terms of mRNA and/or N-Myc oncoprotein. It was recently shown that a small proximal locus mapped between 1p35-36.1 and 1p36.23 may function as a suppressor gene of N-myc amplification. In neuroblastoma, a pattern of diploidy is associated with rapid tumor growth and poor survival. Expression of bcl-2 proto-oncogene is strongly associated with unfavorable histology, while expressions of Ha-ras and trk-A proto-oncogenes indicate a favorable prognosis. trk-A proto-oncogene encodes a receptor for nerve growth factor. Genetic characteristics of neuroblastomas found by urinary catecholamine mass screening are also discussed.
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PMID:Genetic clinical markers of human neuroblastoma with special reference to N-myc oncogene: amplified or not amplified?--An overview. 865 15

Deoxyhpusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Polyamines (putrescine, spermidine, and spermine) have been implicated in tumor growth and differentiation. Because deoxyhypusine/hypusine formation is one of the most specific polyamine-dependent biochemical events, we decided to use N1-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor for deoxyhypusine synthase, to assess the role of hypusine formation on tumor growth and differentiation. GC7 suppressed the growth of N2a mouse neuroblastoma cells and DS19 murine erythroleukemia cells at micromolar concentrations. However, within a narrow concentration range, GC7 could promote the differentiation of mouse neuroblastoma cells in the presence of suboptimal amount of dibutyryl cAMP. In contrast, GC7 blocked the differentiation of DS19 cells induced with hexamethylene bisacetamide. Polyamine depletion by difluoromethyl ornithine (DFMO) has previously been shown to promote differentiation of neuroblastoma cells but inhibits erythrodifferentiation. Since our studies demonstrated that GC7 mimics the action of DFMO on tumor differentiation, it is likely that the effect of DFMO on tumor differentiation is mediated by hypusine formation and that GC7 represents a more specific inhibitor that can alter the differentiation program in certain tumor cells.
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PMID:Effects of inhibitors of deoxyhypusine synthase on the differentiation of mouse neuroblastoma and erythroleukemia cells. 869 49

Amifostine was developed as a radio- and chemoprotective agent. It has shown protection against whole-body irradiation, and myelo- and nephrotoxicity of cytotoxic agents both in experimental and clinical studies. Some experimental trials revealed an influence of amifostine on tumor growth or the activity of cytotoxic drugs under certain circumstances. Therefore, it was the aim of our work to evaluate the pharmacological potential of amifostine in a preclinical in vivo situation with human xenotransplanted neuroblastomas. Human neuroblastoma cells (IMR5-75 and Kelly) were grown s.c. as xenografts in nude mice to palpable sizes (approximately 4 x 5 mm). Then the animals received 200 mg/kg amifostine i.p. and were treated 30 min later with one of the following cytotoxic drugs: cyclophosphamide, doxorubicin, cisplatin, ifosfamide, vincristine and etoposide. Amifostine as the only treatment did not influence the growth of the neuroblastomas IMR5-75 and Kelly. We observed no side effects of the compound itself. In no case did amifostine interact significantly with the antitumor effect of any cytostatic used in combination. However, amifostine mitigated the body weight loss induced by vicristine and the leukopenia induced by cyclophosphamide, cisplatin or ifosfamide, respectively. The side effects of the remaining cytostatics were--if observed at all--unchanged. We conclude that amifostine did not influence the tumor growth of xenotransplanted neuroblastomas and did not reduce the antineoplastic activity of the tested cytostatic drugs. Further investigation of amifostine as a protectant from side effects of chemotherapy in a clinical setting is warranted.
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PMID:Effects of amifostine (WR-2721, ethyol) on tumor growth and pharmacology of cytotoxic drugs in human xenotransplanted neuroblastomas. 907 13

Complete tumor resection is often impossible in disseminated stages of neuroblastoma. Therefore, the role of primary tumor resection in neuroblastoma patients of stage III and IV will be discussed here. Between 1972 and 1995, 66 neuroblastoma patients were operated in our department of pediatric surgery, 41 of whom were treated before 1989 and are the subject of retrospective study. Eight children belonged to stage III, 15 to stage IV and two to stage IV-S. Primary tumor resection was carried out in 19 of 25 patients with disseminated tumor stages. Total resection (RO) was achieved in three cases (16%). Microscopic tumor remains (R1) were present in four, with macroscopic remains in 12 cases. Three disseminated neuroblastomas received preoperative chemotherapeutic treatment, followed by a delayed complete operative tumor resection in two cases. Temporary tumor remission after an incomplete primary operation (R2) was achieved with adjuvant postoperative chemo- and radiotherapy in six of 12 patients. The mortality rate was high (stage III: n = 5/8, stage IV: n = 14/15, stage IV-S: n = 2/2). We recommend preoperative chemotherapy in cases of infiltrative tumor growth of stage III and generally in stage IV. This therapeutic regime improves the rate of complete tumor resection with less intraoperative complications.
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PMID:["As much as possible"--an outdated concept in advanced neuroblastoma?]. 910 81

To elucidate the role gap junctions play in the bystander effect, we examined the cytotoxic effect of herpes simplex virus thymidine kinase (HSVtk) modified tumor cells on gap junction communication-deficient tumor cells and their connexin transfectants. Communication competent Walker 256 tumor cells engineered to express the HSVtk gene (Walker-tk+) when cocultured with N2A mouse neuroblastoma and PC12 rat pheochromocytoma cells with absent endogenous junctional conductance showed no bystander cytotoxicity. Transfection of N2A cells with the rat connexin37 gene (5Q) and PC12 cells with the human connexin43 gene rendered them susceptible to bystander cell death. Additionally, communication-deficient N2A cells transfected with the HSVtk gene failed to exert a bystander effect, whereas N2A transfectants coexpressing the connexin37 and HSVtk genes (5Qtk+ cells) exerted bystander cytotoxicity on gap junction communication-competent 5Q but not on communication-deficient N2A cells in vitro. In vivo experiments also showed tumor growth inhibition of communication-competent 5Q but not communication-incompetent N2A cells by 5Qtk+ cells. In conclusion, these results indicate that in several cellular environments the bystander effect is dependent on connexin expression and gap junctional communication between HSVtk-positive and HSVtk-negative cells.
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PMID:The bystander effect exerted by tumor cells expressing the herpes simplex virus thymidine kinase (HSVtk) gene is dependent on connexin expression and cell communication via gap junctions. 923 Oct 74

SV40 large T-antigen (LTa) gene-induced immortalized rat dopamine-producing nerve cells (IRB3AN27), which produce LTa protein and divide in vitro, do not divide and do not produce LTa protein when transplanted into striatum of adult rats. This suggests the presence of LTa gene-inhibiting factors in brain. Here we report that rat brain soluble fraction (SF) contains factors which specifically inhibit LTa gene activity in vitro. The brain SF inhibited LTa protein levels and the growth of IRB3AN27 cells and 2RSG cells (LTa gene-induced immortalized rat parotid acinar cells) in vitro, but it stimulated the growth of spontaneously immortalized human parotid acinar cells (2HPC8) and had no effect on the proliferation of murine neuroblastoma cells (NBP2) and rat glioma cells (C-6) in culture. In contrast, the liver SF inhibited the growth of all cell lines tested at varying degrees and thus lacked specificity with respect to LTa gene activity. The presence of specific LTa gene-inhibiting factors in the brain and general tumor growth-inhibiting factors in the liver may provide some of the mechanisms of protection against in vivo carcinogenesis.
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PMID:Brain contains inhibiting factors specific to the large T-antigen gene. 946 88

Neuroblastoma, a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behavior, ranging from spontaneous remission to rapid tumor progression and death. To some extent, outcome can be predicted by the stage of disease and age at diagnosis. The molecular events responsible for the variability in response to treatment and rate of tumor growth, however, remain largely unknown. Over the past decade, transformation-linked genetic changes have been identified in neuroblastoma tumors that have contributed to our understanding of tumor predisposition, metastasis, treatment responsiveness, and prognosis. This review discusses the recent advances in the understanding of neuroblastoma at the cellular and molecular levels, and the role that tumor biology plays in determining appropriate risk-based treatment for patients with neuroblastoma.
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PMID:Advances in the diagnosis and treatment of neuroblastoma. 946 84

The human ether-a-go-go-related gene (herg) encodes a K+ current (IHERG) that plays a fundamental role in heart excitability by regulating the action potential repolarization (IKr); mutations of this gene are responsible for the chromosome 7-linked long QT syndrome (LQT2). In this report, we show that in a variety (n = 17) of tumor cell lines of different species (human and murine) and distinct histogenesis (neuroblastoma, rhabdomyosarcoma, adenocarcinoma, lung microcytoma, pituitary tumors, insulinoma beta-cells, and monoblastic leukemia), a novel K+ inward-rectifier current (IIR), which is biophysically and pharmacologically similar to IHERG, can be recorded with the patch-clamp technique. Northern blot experiments with a human herg cDNA probe revealed that both in human and murine clones the very high expression of herg transcripts can be quantified in at least three clearly identifiable bands, suggesting an alternative splicing of HERG mRNA. Moreover, we cloned a cDNA encoding for IIR from the SH-SY5Y human neuroblastoma. The sequence of this cDNA result was practically identical to that already reported for herg, indicating a high conservation of this gene in tumors. Consistently, the expression of this clone in Xenopus oocytes showed that the encoded K+ channel had substantially all of the biophysical and pharmacological properties of the native IIR described for tumor cells. In addition, in the tumor clones studied, IIR governs the resting potential, whereas it could not be detected either by the patch clamp or the Northern blot techniques in cells obtained from primary cell cultures of parental tissues (sensory neurons and myotubes), whose resting potential is controlled by the classical K+ anomalous rectifier current. This current substitution had a profound impact on the resting potential, which was markedly depolarized in tumors as compared with normal cells. These results suggest that IIR is normally only expressed during the early stages of cell differentiation frozen by neoplastic transformation, playing an important pathophysiological role in the regulatory mechanisms of neoplastic cell survival. In fact, because of its biophysical features, IIR, besides keeping the resting potential within the depolarized values required for unlimited tumor growth, could also appear suitable to afford a selective advantage in an ischemic environment.
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PMID:herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells? 948 40


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