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)

Several transcription regulatory elements that interact with cellular DNA-binding proteins have been identified in the HIV-1 long terminal repeat (LTR). We have identified two sequence motifs in the U3 region of the LTR that are similar to the consensus 9-bp DNA-binding element of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. One of the sequences (promoter-proximal) mapped immediately upstream of the NF-kappa B element, whereas the other (promoter-distal) completely overlapped the upstream stimulatory factor (USF) binding site. In this study, we investigated the role of the enhancer-proximal consensus C/EBP binding sequence in the expression of the HIV-1 LTR. In cotransfection assays we found that although this sequence is a functional C/EBP-responsive element, the regulation of the HIV promoter by C/EBP is very complex. C/EBP isoforms inhibited the phorbol 12-myristate 13-acetate (PMA)-stimulated HIV-1 promoter activity in human glioblastoma U138MG and neuroblastoma SHSY5Y cells, but not in HeLa epithelial cells, and this inhibition required the NF-kappa B element. C/EBP also downregulated the HIV NF-kappa B element-containing SV40 early promoter activity, regardless of the presence of the flanking C/EBP-binding sequences, in the two brain-derived cells. In electrophoretic mobility shift assays with nuclear extracts from HeLa and U138MG cells, purified C/EBP markedly increased the complex formation between endogenous proteins and the NF-kappa B DNA probe without detectable association with the complex. However, with extracts from U138MG cells but not from HeLa cells, a slow migrating complex was observed. Our data suggest that the C/EBP family of transcription factors can downregulate the HIV-1 promoter activity in CNS-derived cells through the NF-kappa B binding elements.
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PMID:NF-kappa B site-mediated negative regulation of the HIV-1 promoter by CCAAT/enhancer binding proteins in brain-derived cells. 757 67

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.
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PMID:Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. 757 68

Expression of the RCK gene, which is a target gene on 11q23 of the t(11;14) (q23;q32) translocation in the B-cell lymphoma cell line RC-K8, was studied by Northern and Western blot analyses. The RCK gene product is a member of the D-E-A-D box protein/RNA helicase family. With the use of Northern blot analysis, a 7.5-kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against the RCK gene product were raised, and the RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal anti-rck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues, although RCK mRNA is abundantly present in these tissues. It is of interest that malignant transformed human cells arising from tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma, and lung cancer cell lines, produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role in tumorigenesis. In addition, the rck/p54 protein was localized to cytoplasm by immunostaining with the use of laser microscopy and by subcellular fractionation.
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PMID:The rck/p54 candidate proto-oncogene product is a 54-kilodalton D-E-A-D box protein differentially expressed in human and mouse tissues. 761 84

Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, is a multipotent polypeptide which elicits mitogenic, motogenic, and morphogenic activities for various types of cells. To better understand the biological activity of HGF, as related to neuroectodermal-derived cells, we investigated the effects of HGF on rat pheochromocytoma PC12 cells. HGF increased the number of PC12 cells during long culture, but elicited no direct mitogenic activity, as determined by DNA synthesis. When the cells were cultured in medium containing lower concentrations of fetal calf serum, HGF prolonged the survival of PC12 cells; the number of cells did not decrease during 13 days when the cells were cultured in the presence of HGF, but the cells were completely withdrawn when cultured in the absence of HGF. Nerve growth factor but not HGF induced the differentiation of PC12 cells. High affinity receptor for HGF with Kd values of 20-40 pM was expressed in PC12 cells and other types of cells derived from the central nervous tissue: T98G cells (human glioblastoma), GOTO, and SCCH-26 cells (human neuroblastoma). HGF stimulated motility of T98G cells, while it induced weak mitogenic response in GOTO cells. We suggest that HGF is a potent survival factor for PC12 cells, without exerting any direct mitogenic activity and inducing the cell differentiation, and that this factor may have a distinct biological activity for neuroectoderm-derived cells.
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PMID:Hepatocyte growth factor as a potent survival factor for rat pheochromocytoma PC12 cells. 766 45

Thirteen tumor-derived cell lines of human and nonhuman origin and from various tissues were examined for the presence and density of sigma-1 and sigma-2 receptors. Sigma-1 receptors of a crude membrane fraction were labeled using [3H](+)-pentazocine, and sigma-2 receptors were labeled with [3H]1,3-di-o-tolylguanidine ([3H]DTG); in the presence or absence of dextrallorphan. [3H](+)-Pentazocine-binding sites were heterogeneous. In rodent cell lines (e.g., C6 glioma, N1E-115 neuroblastoma, and NG108-15 neuroblastoma x glioma hybrid), human T47D breast ductal carcinoma, human NCI-H727 lung carcinoid, and human A375 melanoma, [3H](+)-pentazocine bound to high- and low-affinity sites with Kd1 = 0.67-7.0 nM, Bmax1 = 25.5-108 fmol/mg protein, Kd2 = 127-600 nM, and Bmax2 = 942-5431 fmol/mg protein. However, [3H](+)-pentazocine bound to a single site in other cell lines. In human U-138MG glioblastoma, SK-N-SH neuroblastoma, and LNCaP.FGC prostate, Kd = 28-61 nM and Bmax = 975-1196 fmol/mg protein, whereas in ThP-1 leukemia Kd = 146 nM and Bmax = 1411 fmol/mg protein. The sigma-1-like nature of [3H](+)-pentazocine-binding sites was confirmed by competition studies which revealed high affinity for haloperidol and enantioselectivity for (+)-pentazocine over (-)-pentazocine. Interestingly, human MCF-7 breast adenocarcinoma showed little or no specific binding of [3H](+)-pentazocine, suggesting the absence of sigma-1 receptors in this cell line. All cell lines examined expressed a high density of sigma-2 receptors with Kd values for [3H]DTG ranging from 20 to 101 nM and Bmax values of 491 to 7324 fmol/mg protein. Competition studies indicated possible heterogeneity of sigma-2 receptors. While sites labeled by [3H]DTG in all cell lines tested exhibited affinity for haloperidol and preference for (-)-pentazocine over the (+)-enantiomer, human cell lines generally showed 4- to 7-fold lower affinity for haloperidol and approximately 10-fold lower affinity for (-)-pentazocine compared with the rodent cell lines. The high density of sigma-1 and sigma 2-binding sites in these cell lines suggests important cellular functions in cancer, as well as potential diagnostic utility for tumor-imaging agents which target sigma sites. These cell lines may be useful as model systems in which to study the functions of sigma sites in normal tissues, as well as their possible role in tumor biology.
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PMID:Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. 781 73

A monoclonal antibody 6DS1 against a human glioblastoma multiforme cell line U-87MG recognizes a tumor-specific, cell surface antigen of human glioblastoma cell lines. Partial cross-reactivity is observed with two human neuroblastoma cell lines, SK-N-SH and SK-N-MC, with little or no reactivity towards a rat glioma cell line C6 or normal human adult and fetal brain tissues. The antibody recognizes an antigen of molecular mass 38 kDa as inferred from Western blot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate. The monoclonal antibody 6DS1 inhibits both the attachment to substratum and growth of U-87MG cells. It strongly cross-reacts with xenotransplants of U-87MG cells and inhibits tumorigenesis (subcutaneous implants of U-87MG cells) in nude mice.
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PMID:Monoclonal antibody against human glioblastoma multiforme (U-87MG) immunoprecipitates a protein of molecular mass 38 kDa and inhibits tumor growth in nude mice. 782 86

The activity of IMP dehydrogenase (EC 1.2.1.14), the key enzyme of de novo guanylate biosynthesis, was shown to be increased in tumor cells. Tiazofurin (TR), a potent and specific inhibitor of this enzyme, proved to be effective in the treatment of refractory granulocytic leukemia in blast crisis. We examined the effects of tiazofurin as a single agent and in combination with hypoxanthine and allopurinol in six different neuroectodermal tumor cell lines, the STA-BT-3 and 146-18 human glioblastoma cell lines, the SK-N-SH, LA-N-1 and LA-N-5 human neuroblastoma cell lines, and the STA-ET-1 Ewing tumor cell line. Tiazofurin inhibited tumor cell growth with IC50 values between 2.2 microM (LA-N-1 cell line) and 550 microM (LA-N-5 cells) and caused a significant decrease of intracellular GTP pools (GTP concentrations decreased to 39-79% of control). Incorporation of [8-14C]guanine into GTP pools was determined as a measure of guanylate salvage activity; incubation with 100 microM hypoxanthine caused a 62-96% inhibition of the salvage pathway. Incubation with tiazofurin (100 microM) and hypoxanthine (100 microM) synergistically inhibited tumor cell growth, and the addition of allopurinol (100 microM) strengthened these effects. Therefore, this drug combination, inhibiting guanylate de novo and salvage pathways, may prove useful in the treatment of human neuroectodermal tumors.
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PMID:Synergistic action of tiazofurin with hypoxanthine and allopurinol in human neuroectodermal tumor cell lines. 790 33

We investigated the distribution of 111In-pentetreotide (Octreoscan, Mallinckrodt) in nude mice xenografted with a human neuroblastoma cell line (SKLAN, derived from the LAN1 line). These cells develop into solid tumours in nude mice and can be grafted repeatedly in grafts of 10(8) cells. Animals were sequentially explored by scintigraphy 2, 4, 24 and 48 hr after i.v. injection of 2.5-4 MBq of the tracer and killed at various times up to 48 hr. 111In-pentetreotide was rapidly and strongly taken up by all tumours, with a tumour/muscle (T/M) ratio on resected samples of 20.0 +/- 5.7 at 2 hr, 23.7 +/- 3.0 at 4 hr, 75.6 +/- 12.6 at 24 hr and 78.7 +/- 12.4 at 48 hr, for tumours ranging from 0.5 to 8 g. Scintigraphy results were quantitatively in agreement. Pre-injection of a 15-20 times larger quantity of unlabelled octreotide s.c. reduced the tumour uptake by a factor of 2. For comparison, nude mice xenografted with the same cell line were also studied with 123I-MIBG (4 MBq). At 24 hr, the T/M ratio was 0.62 +/- 0.18. Two other cell lines (glioblastoma ROM and small-cell lung carcinoma SC41) which were similarly tested with 111In-pentetreotide (2.5-4 MBq) gave T/M ratios at 24 hr of 4.8 +/- 2.8 and 38.4 +/- 21.8, respectively. Pentetreotide seems to have a high affinity for this MIBG-negative neuroblastoma cell line, which exhibited a clearly higher tumour uptake than the 2 other lines. This work provides new experimental arguments in favour of the particular interest of somatostatin analogues in neuroblastoma and confirms our first clinical results.
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PMID:Strong uptake of 111In-pentetreotide by an MIBG-negative, xenografted neuroblastoma. 790 95

Investigations on the general characteristics of human astrocytoma cell line NAC-1 revealed neuroblastoma growth inhibitory activity in conditioned medium. Neuroblastoma growth inhibitory factor (NGIF) was partially purified by Econo Q, Econo CM, and Superose 12 column chromatography. The protein is weakly basic with an estimated M(r) of 120,000, possibly having an M(r) 60,000 dimeric structure. NGIF inhibits the growth of human neuroblastoma cell lines but has no effect on morphology nor does it produce any change in the growth of human glioblastoma cell lines. Interestingly, NGIF appears to promote survival and neurite outgrowth of embryonal rat cortical neurons. These neurotrophic properties suggest a role for NGIF in the development of the nervous system.
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PMID:Human neuroblastoma growth inhibitory factor (h-NGIF), derived from human astrocytoma conditioned medium, has neurotrophic properties. 805 39

Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by flow cytometric analysis and 125I-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (KD = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers.
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PMID:Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. 805 54


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