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)

CD24 antigen is a glycoprotein expressed on haematopoietic cells, including B cells, T cells and granulocytes and on non-haematopoietic cells, including neural cells, ganglion cells and the cells of the adrenal medulla. The antigen is also expressed on renal cell carcinoma, small cell lung carcinoma and neuroblastoma. We have cloned rat cDNA encoding core polypeptide of CD24 antigen from embryonic brain and shown that the core molecule is highly expressed in embryonic brain and non-neural tissues. Rat tissue and various human neoplastic cell lines were investigated for the gene expression of CD24 core polypeptide by in situ hybridization. The transcript was localized in gastrointestinal epithelia, ductal and acinar epithelia of the salivary gland, the bronchiolar epithelium, renal tubular epithelium, the epithelium of the oviduct, follicular cells of the thyroid, medullary cells of the adrenal gland, Auerbach's plexus, B blastoid cells in lymph nodes, hair follicles, and the sweat glands of the skin. Among the various human neoplastic cell lines investigated, the transcript was detected in squamous cell carcinoma of the lung, gastric carcinoma, colon carcinoma, choriocarcinoma and renal cell carcinoma. The result suggest that the core molecule of CD24 antigen may be expressed in a wider range of epithelial cells and carcinoma cell lines than has been reported. Furthermore, we show that gene expression of CD24 core polypeptide is confined to the proliferative zone of the gastrointestinal mucosa, suggesting that core molecule is transiently expressed on the surface of epithelial cells in the process of cellular maturation. We discuss a possible role for CD24 antigen in the maturation of epithelial cells in the gastrointestinal tract.
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PMID:Gene expression of CD24 core polypeptide molecule in normal rat tissues and human tumor cell lines. 782 Mar 2

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.
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PMID:Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells. 782 19

We have tested 29 patients with the Lambert-Eaton myasthenic syndrome (LEMS) for serum antibodies to voltage-gated calcium channels (VGCC) using an immunoprecipitation assay in which [125]-omega-conotoxin GVIA is used to label calcium channels extracted from IMR-32, a human neuroblastoma cell line. Fifty-five percent of these patients had significant levels of antibody [31.6 (26.5, 48.2) (med., Q1, Q3) pmol/L, n = 29], compared with healthy controls [21.5 +/- 3.4 (mean +/- SD) pmol/L, n = 30] and other neurological disorders [25.2 +/- 4.2 (mean +/- SD) pmol/L, n = 10]. These antibodies were found in 43% of the patients with small cell lung carcinoma (SCLC) without signs and symptoms of LEMS [32.2 +/- 7.2 (mean +/- SD) pmol/L n = 30] and 7% of the myasthenic patients [21.4 +/- 6.8 (mean +/- SD) pmol/L n = 14]. Anti-VGCC antibody titers did not correlate with presence of SCLC, disease duration, or an electromyographic index of disease severity. Our results suggest that the antibodies detected in this assay are specific to some patients with LEMS, but not all. This assay is a useful aid in diagnosing LEMS but has much room for improvement.
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PMID:[Anti-voltage-gated calcium channel antibodies in the Lambert-Eaton myasthenic syndrome]. 783 58

We have searched for novel genetic alterations in human cancer cell lines by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. A homozygous deletion was detected in a small-cell lung carcinoma (SCLC) cell line, NCI-H82. Since homozygous deletion is a critical genetic alteration for the inactivation of tumor suppressor gene, we defined the locus of homozygous deletion. Fluorescence in situ hybridization analysis revealed that the deletion was localized at chromosome 2q33. Allelic loss on chromosome 2q was detected in 29.4% (5/17) of SCLC and 37.5% (12/32) one non-SCLC by restriction fragment length polymorphism analysis. Considerably high incidence of allelic loss on chromosome 2q was also detected in colorectal carcinoma and neuroblastoma. These results suggest the presence of a novel tumor suppressor gene at 2q33, which is involved in the development of several human cancers. The size of the homozygous deletion in the NCI-H82 cell line was more than 20 kilobase pairs. Seven loci mapped to 2q32-qter were all retained in this cell line, suggesting the presence of submicroscopic interstitial deletion in this cell line. Homozygous deletion detected in this study should be an invaluable tool for positional cloning of the target tumor suppressor gene at 2q33.
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PMID:Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic fingerprinting. 790 18

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

Since the introduction of the hybridoma technology by Kohler and Milstein (Nature 1975, 256, 495-497), tremendous effort has been put in the realisation of Ehrlich's concept of the magic bullet, which was proposed as early as the beginning of the century. The first clinical studies for radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) with radiolabelled antibodies were undertaken in the early 1980s. Since then, RIS has been performed on thousands of patients with various types of malignancies, like colon carcinoma, lung carcinoma, breast carcinoma, neuroblastoma, T-cell lymphoma and ovarian carcinoma. In addition, a substantial number of therapy trials with radiolabelled antibodies have been performed. The developments for head and neck squamous cell carcinoma (HNSCC) have only recently been able to catch up with these events to some extent. One of the main reasons for this slow progress has been the lack of monoclonal antibodies (Mab) with specificity for HNSCC. Although there are as yet no real tumour specific antigens known for HNSCC, which also holds true for the majority of malignancies arising from other tissues, we now have the availability of a number of Mab with high specificity for HNSCC and with a very restricted reaction pattern with normal tissues. Labelled with 131I, these Mab have been shown to be highly capable to localise in HNSCC xenografts in nude mice. Based on these promising data, patient studies with one of these Mab, designated Mab E48, labelled with 99mTc, were started to evaluate the feasibility of RIS in patients with head and neck cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The feasibility of radioimmunotherapy of head and neck cancer. 803 5

The neural cell adhesion molecule (N-CAM), a member of the immunoglobulin gene super-family mediating homophilic cell-cell adhesion in a neuroendocrine system, is preferentially expressed in human small cell lung cancer (SCLC). Immunoprecipitation of a panel of SCLC cell lines by monoclonal antibodies (mAbs) specific for N-CAM detects mainly the 145-kDa isoform. This result was correlated with Northern blotting where a single 6.2-kb mRNA was detected in nine SCLC cell lines. To determine cDNA sequence encoding the N-CAM isoform, we selected several cDNA clones encoding N-CAM isolated from OS2-R, a SCLC cell line established in our laboratory. Based on the analysis of the full-length cDNA obtained from two clones, the sequence of this 145-kDa isoform was shown to be essentially identical to that of the 140-kDa N-CAM isoform of neuroblastoma except for a single base pair changed at position 1620 without changing amino acid encoded.
Lung Cancer 1994 Mar
PMID:Complementary DNA sequence encoding the major neural cell adhesion molecule isoform in a human small cell lung cancer cell line. 807 73

Gastrin releasing peptide is mitogenic for mouse Swiss 3T3 fibroblasts and certain human small cell lung carcinoma (SCLC) cells but not for mouse Balb/c 3T3 fibroblasts. To identify new molecules associated with the gastrin releasing peptide-responsive phenotype, clones isolated from a differential cDNA library between Swiss and Balb/c 3T3 fibroblasts were used to screen for their expression in human SCLC cell lines. Using this approach, we have isolated and characterized human and mouse cDNA clones encoding a novel protein. This protein is a putative transmembrane protein belonging to the epidermal growth factor-like superfamily. In vitro transcription and translation studies detect a 42-kDa protein, in agreement with the size predicted from the translated cDNA sequence. This protein (termed Delta-like or dlk) is highly homologous to invertebrate homeotic proteins, including Delta, and Notch, the products of neurogenic loci involved in normal neural differentiation in Drosophila. dlk is expressed in tumors with neuroendocrine features, such as neuroblastoma, pheochromocytoma, and a subset of SCLC cell lines. However, its expression in normal tissues is restricted to the adrenal gland and placenta. These data suggest that dlk may be involved in neuroendocrine differentiation and, because of its cellular location and restricted expression in normal tissues, it may be a potential therapeutic target in neuroendocrine tumors, particularly SCLC.
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PMID:dlk, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. 809 43

The N-myc gene is amplified and overexpressed in neuroblastoma, retinoblastoma and small cell lung carcinoma, and is considered to be related to cell proliferation and/or differentiation. The transcriptional regulatory sequences of the c-myc gene have been already identified, while those of N-myc have remained obscure for a long time. In this report, we have identified several positive and negative transcriptional regulatory elements in the upstream region of the mouse N-myc gene. Among them, an activating sequence spanning -860 to -797 bp (63 bp) could be reduced to a functional core of 21 bp from -846 to -826. This sequence, termed N21 box, worked as a positive transcriptional element when linked directly upstream (but not downstream) of the putative N-myc promoter in HeLa, not in IMR32 cells. At least two proteins, of 42 kDa and 100 kDa, bound to the double-stranded N21 box, and were expressed in HeLa as well as in IMR32 cells. Moreover, the plus strand of N21 box could be specifically bound by a species of 42 kDa from either cell type and by a 37 kDa protein found only in HeLa cells. These proteins may be factors binding to positive transcriptional regulatory elements and may have a role in the regulation of N-myc expression.
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PMID:Transcriptional regulation of the N-myc gene: identification of positive regulatory element and its double- and single-stranded DNA binding proteins. 824 Dec 68

The fate of anti-tumor monoclonal antibodies (mAbs) after binding to the cell surface is one of the important factors for application of mAbs in therapy. For mAbs to remain on the cell surface for a long time is preferable character for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). On the other hand, quick internalization of mAbs into cytoplasm is advantageous for cytotoxic effects of toxins or cytotoxic drugs conjugated with mAbs. In this study we investigated the localization of anti-carbohydrate mAbs in vitro by immunocytochemical methods at the electron microscopic level. Anti-ganglioside GM3 mAb (mouse IgM) was localized both in cytoplasmic vesicles and on the cell surface membrane of mouse melanoma cells after incubation for 30 min at 37 degrees C. Anti-ganglioside GM2 mAb (mouse IgM), anti-ganglioside GD2 mAb (mouse IgG3) anti-ganglioside GD3 mAb (mouse IgG3) mainly existed on the cell surface of human small cell lung carcinoma cells, human neuroblastoma cells and human melanoma cells, respectively, after incubation for 30 min at 37 degrees C. On the other hand, anti-sialyl Lea mAb (mouse IgG1) was intensively incorporated into the cytoplasm of human colon tumor cells under the same conditions. Anti-ganglioside GD3 mAb and anti-sialyl Lea mAb were radiolabelled with 125Iodine and traced in in vitro culture. When the cells were incubated in the presence of the 125I-mAb for 90 min on ice, the ratio of intracellular counts to surface counts was 8/92 for anti-ganglioside GD3 mAb and 31/69 for anti-sialyl Lea mAb respectively. After the subsequent incubation for 60 min at 37 degrees C, the ratio altered to 13/87 for anti-ganglioside GD3 mAb and 54/46 for anti-sialyl Lea antigen mAb. This study suggested that internalization of anti-carbohydrate mAbs after the binding to the cell surface was different among the mAbs depending on the character of antigens. In conclusion, anti-ganglioside mAbs have beneficial characters for CDC or ADCC while anti-sialyl Lea mAb is suitable for immunoconjugates.
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PMID:Immunocytochemical study on internalization of anti-carbohydrate monoclonal antibodies. 829 35


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