Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera from a patient with systemic lupus erythematosus (SLE), tested by indirect immunofluorescence on frozen tissue sections, gave granular cytoplasmic staining of hepatocytes, gastric chief cells, exocrine cells of the pancreas and submandibular glands, and cerebellar Purkinje cells. In acetone-fixed monolayers of rat embryonic fibroblasts, 3T3 cells, mouse neuroblastoma cells, and cells from a human melanoma and colon carcinoma cell line, the sera stained perinuclear cytoplasmic granules which radiated out towards the cell periphery. More mature and differentiated fibroblasts from rat of human foetal lung showed staining of reticular cytoplasmic structures corresponding to phase-dense rough endoplasmic reticulum (RER). Nucleoli were prominently stained in all cultured cells. Serum absorption with ribosomes inhibited all antibody activity but absorption with RNA or with RNase-treated ribosomes resulted only in partial inhibition. Monolayers of RNase-treated fibroblasts gave weaker staining reactions compared to control untreated cultures. These observations suggest that the autoantibody is directed against ribosomal RNA and ribosomal protein present in cytoplasmic polyribosomes, in RER and in nucleoli.
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PMID:Autoantibody to ribosomes and systemic lupus erythematosus. 700 92

Retinoic acid (RA) has profound effects on cell proliferation and differentiation both in vitro and in vivo. Many human cell lines are known to be sensitive to the growth-inhibitory action of RA. We analyzed established human solid tumor-derived cell lines for their RA sensitivity. Growth inhibition by RA in monolayer was examined by [3H]thymidine incorporation and cell proliferation. Here we report that 11 widely used human cell lines were RA resistant. The majority are carcinoma derived (A-431, BT-20, C-41, ACHN, HCT116, 293, A549, and PA-1); two are sarcoma derived (Saos-2 and A673); and one is a melanoma cell line (A-375). Since nuclear retinoid receptors are implicated in the biological effects of RA, we examined the expression of retinoic acid receptors (RARs) RAR alpha, RAR beta, RAR gamma, and the retinoid X receptors (RXRs) RXR alpha, RXR beta, and RXR gamma in the RA-resistant cell lines by northern blotting and by RNase protection analysis for RAR beta. RAR alpha transcripts were constitutively expressed in all cell lines. By contrast, RAR beta was expressed in only seven RA-resistant cell lines (Saos-2, ACHN, 293, A549, A-375, A673, and PA-1), and its level was enhanced by RA in some cases. In most cell lines, RAR gamma expression was low and was not affected by RA. The RXR genes showed a very distinct expression pattern in the group of selected cell lines. In general, RXR alpha was the most abundantly expressed subtype, RXR beta was expressed at low levels, and RXR gamma could not be detected. In none of the RA-resistant cell lines was RXR expression modulated by RA. The results presented here indicate that the resistance of these human tumor cell lines to RA cannot be simply correlated with expression of RAR or RXR or both.
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PMID:Retinoic acid receptor and retinoid X receptor expression in retinoic acid-resistant human tumor cell lines. 769 Oct 69

The beta1,4-N-acetylgalactosaminyltransferase (beta1,4GalNAc-T) (EC) gene is expressed in normal brain tissues and in various malignant transformed cells, such as malignant melanoma, neuroblastoma, and adult T cell leukemia. To analyze the regulatory mechanisms of gene expression, we determined the genomic organization of the beta1, 4GalNAc-T gene. The gene consists of at least 11 exons and spans >8 kilobase pairs. The coding region is located in exons 2-11. To determine the transcription initiation sites, 5'-rapid amplification of cDNA ends analysis and ribonuclease protection assays were performed using RNA obtained from the human melanoma cell line SK-MEL-31. Consequently, we defined three transcription initiation sites and the alternative usage of three exons. Exons 1a and 1b partially overlap; the latter is part (3'-side) of the former and corresponds to the 5'-noncoding region of the cDNA clone previously isolated. The third transcript, exon 1c, corresponds to nucleotides -520 to -412 (position +1 = A of ATG of beta1,4GalNAc-T cDNA), which are considered to be in intron 1 based on the cloned cDNA sequence. Ribonuclease protection assays revealed the corresponding protection bands in samples of the gene-expressing cell lines. 5'-Flanking regions of individual initiation sites showed promoter activity when analyzed by chloramphenicol acetyltransferase assay in SK-MEL-31 cells. The multiple transcription initiation sites and their promoters/enhancers identified here might be differentially involved in the cell type-specific expression of the beta1,4GalNAc-T gene. This gene was assigned to human chromosome 12q13.3 by means of fluorescence in situ hybridization.
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PMID:Genomic organization and chromosomal assignment of the human beta1, 4-N-acetylgalactosaminyltransferase gene. Identification of multiple transcription units. 870 39

The genomic structure, transcription start site, polyadenylation signals, and promoter of the human Na+/ myo-inositol cotransporter (SLC5A3) gene have been elucidated through cloning, sequencing, mRNA analyses, and reporter gene assays. The gene consists of one promoter and two exons spanning approximately 26 kb. Exon 1 contains 175 bp of 5' untranslated sequence and is 15 kb upstream of exon 2. The 9.5-kb exon 2 contains the entire 2157-bp open reading frame and a large 3' untranslated sequence with seven putative polyadenylation signals. Multiple messages with different-sized 3' untranslated regions can be detected on Northern blots. Hypertonic stress caused mRNA levels, and primarily that of the full-length 9.5-kb transcript, to increase in cultured melanoma cells; ribonuclease protection analysis demonstrated that the transcription start site was the same in stressed as in control cells. The SLC5A3 gene functions in cellular osmoregulation and is expressed in many human tissues including the brain, kidney, and placenta. It is localized to chromosome 21q22.1. An overexpression of the SLC5A3 gene deserves consideration as a factor in the pathophysiology of Down syndrome.
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PMID:The structural organization of the human Na+/myo-inositol cotransporter (SLC5A3) gene and characterization of the promoter. 944 50

This paper reports on the antitumor activity of BS RNase on human melanoma and mouse seminoma. Human melanoma cells established in culture were extremely susceptible to BS RNase, administered in concentrations ranging from 1-100 microg/ml. Concentrations of BS RNase over 10 microg/ml caused complete inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype of the ribonuclease superfamily, did not exert any effect under these conditions. Based on our previous results, athymic mice bearing human melanoma or mouse seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg b.w.). This dose was injected for five consecutive days excluding weekends. The intratumoral administration of BS RNase to nude mice bearing human melanoma showed a significant antitumor effect. There were no tumors seen in eighty percent of mice treated for three weeks, and tumors in the other mice diminished significantly. After some delay the tumors started to regrow. Prolonging of the treatment to five weeks had a similar effect. The effect of BS RNase on mouse seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to eliminate tumors in all treated mice. However, as in the previous experiment, the growth of tumor tissue later reappeared.
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PMID:Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma. 960 99

We determined the expression of a newly recognized drug resistance gene, the multidrug resistance-associated protein (MRP) gene, [Cole et al., Science (Washington DC), 258: 1650-1654, 1992], in normal human tissues and in >370 human tumor biopsies using a quantitative RNase protection assay and immunohistochemistry. MRP mRNA appeared to be ubiquitously expressed at low levels in all normal tissues, including peripheral blood, the endocrine glands (adrenal and thyroid), striated muscle, the lymphoreticular system (spleen and tonsil), the digestive tract (salivary gland, esophagus, liver, gall bladder, pancreas, and colon), the respiratory tract (lung), and the urogenital tract (kidney, bladder, testis, and ovary). The human cancers analyzed could be divided into three groups with regard to MRP expression. Group 1 consists of tumors that often exhibit high to very high MRP mRNA levels (e.g., chronic lymphocytic leukemia). Group 2 comprises the tumors that often exhibit low, but occasionally exhibit high MRP mRNA expression (e.g., esophagus squamous cell carcinoma, non-small cell lung cancer, and acute myelocytic leukemia). Group 3 comprises the tumors with predominantly low levels of MRP mRNA, comparable to the levels found in normal tissues (e.g., other hematological malignancies, soft tissue sarcomas, melanoma, and cancers of the prostate, breast, kidney, bladder, testis, ovary, and colon). Using the MRP-specific mAbs MRPr1 and MRPm6, we confirmed the elevated MRP mRNA levels in tumor tissues by immunohistochemistry. We conclude that hyperexpression of MRP is observed in several human cancers, and that additional studies are needed to assess the clinical relevance of MRP.
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PMID:Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. 981 25

Unlike the bovine pancreatic ribonuclease (RNAase A), bovine seminal ribonuclease (BS RNAase) displays various biological activities including antitumor cytotoxicity. To learn more about its antitumor activity, we investigated BS RNAase effect on athymic nude mice bearing various tumors. BS RNAase (250 micrograms per mouse per day) was administered to the mice with prostate carcinoma for three weeks by three different routes (intraperitoneally--i.p., subcutaneously--s.c., and intratumorally-i.t.). Administration i.p. was ineffective, while s.c. administration reduced significantly size of tumors and i.t. administration abolished half of the tumors in treated mice. The i.t. administration of BS RNase to nude mice bearing melanoma showed even better results. Eighty % of mice were without tumors and in the other mice the tumors were significantly diminished. The best antitumor effect was obtained in case of seminoma. All mice bearing this tumor were cured after ten doses of BS RNAase.
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PMID:Antitumor action of bovine seminal ribonuclease. 982 13

Tumor vascularization is accompanied by the migration of stromal cells, including endothelial cells, smooth muscle cells, and fibroblasts, into the tumor. The biological contributions of stromal cells to tumor vascularization have not been well-defined, partly due to the difficulty of culturing stromal cells in the presence of large numbers of fast-growing tumor cells. To address this problem, a strategy was devised to kill tumor cells but not stromal cells. Advantage was taken of the observation that diphtheria toxin (DT) kills human but not rodent cells. Human melanoma (MMAN) tumor cells were injected subcutaneously into nude mice. The tumors were excised, homogenized, and treated with 50 ng/ml DT for 24 hours. Elimination of melanoma cells by DT treatment was demonstrated by lack of detectable levels of microphthalmia, a transcription factor that is a marker for melanoma cells. The murine stromal cells were viable and found to be mostly smooth muscle cells. These cells constituted about 1.5% of the MMAN tumor. RNase protection assays using a specific murine vascular endothelial growth factor probe confirmed the murine origin of the stromal cells. This method allows rapid isolation of stromal cells and should facilitate biochemical and genetic analysis of tumor-stromal interactions.
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PMID:Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity. 1048 30

Pancreatic-type RNases are considered to have cytotoxic potential due to their ability to degrade RNA molecules when they enter the cytosol. However, most of these RNases show little cytotoxicity because cells have no active uptake mechanism for these RNases and because the ubiquitous cytoplasmic RNase inhibitor is considered to play a protective role against the endocytotic leak of RNases from the outside of cells. To study the cytotoxic potential of RNase toward malignant cells targeting growth factor receptors, the C-terminus of human RNase 1 was fused to the N-terminus of human basic fibroblast growth factor (bFGF). This RNase-FGF fused protein effectively inhibited the growth of mouse melanoma cell line B16/BL6 with high levels of cell surface FGF receptor. This effect appeared to result from prolongation of the overall cell cycle rather than the killing of cells or specific arrest in a particular phase of the cell cycle. Thus, human RNase 1 fused to a ligand of cell surface molecules, such as the FGF receptor, is shown to be an effective candidate for a selective cell targeting agent with low toxic effects on normal cell types.
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PMID:Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor. 1058 8

Immunostaining of the cell cycle-associated Ki-67 antigen was studied, using the Ki-67-specific MIB-1 monoclonal antibody on slides prepared by cytocentrifugation of cultured A375 melanoma cells. Immunomorphological analysis of the Ki-67 immunostaining pattern of both nuclear and nucleolar locations was carried out following pre-treatment of the slides including ribonuclease and deoxyribonuclease pre-digestion of the cells. Immunostaining of nucleolar Ki-67 was reduced by ribonuclease pre-digestion, but was not altered by deoxyribonuclease pre-treatment. Ribonuclease did not reduce the staining intensity of Ki-67 in the nuclear matrix, but the intensity decreased after deoxyribonuclease pre-digestion. We suggest that the Ki-67 molecule may play an important role in ensuring contact between nuclear DNA and nucleolar RNA during transcriptional processes in cell proliferation.
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PMID:Effect of Ribonuclease A and Deoxyribonuclease I on Immunostaining of Ki-67 in Cultured Melanoma Cells. 1117 87


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