Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the treatment of HeLa cells with a tumor-promoting phorbol ester, 12-o-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the genes for the calpain family has been examined. Among the mRNAs for the calpain family, only the mRNA for the large subunit of human m-calpain (calpain mL) was specifically induced by treatment of cells with TPA, suggesting its specific function in response to cellular stimuli. The effect of TPA on the expression of the calpain mL gene was further examined using fusion genes containing the promoter/enhancer region of the calpain mL gene fused upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene, showing that the promoter/enhancer sequence of the calpain mL gene contains a cis-acting element which responds to TPA and activates transcription of the downstream sequence.
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PMID:Transcriptional activation of the gene for the large subunit of human m-calpain by 12-o-tetradecanoyl-phorbol-13-acetate. 161 29

The past year has seen important advances in our understanding of the molecular biology of human cancer. We have learned more about how normal genes with critical functions in growth and development can induce cellular transformation and malignancy if mutated or overexpressed. The finding of such oncogenes in specific human cancers often portends a poor prognosis. We have learned more about tumor suppressor genes, whose loss by mutation, deletion, or translocation can lead to cancer. A series of defects involving both oncogenes and tumor suppressor genes has been shown to characterize the multistep development of a fully malignant colon cancer. We have new insights into the promotion of malignancy by the fused gene product resulting from the chromosomal abnormality diagnostic of one leukemia, chronic myelogenous leukemia. Recently, in acute promyelocytic leukemia, a characteristic chromosomal abnormality has been shown to result in a specific fusion of a nuclear receptor that activates transcription and a previously unknown gene. Most interestingly, a ligand for this rearranged receptor has been shown to be a novel effective treatment for the disease. This review summarizes many of these advances.
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PMID:Oncogenes and clinical oncology. 164 34

RNA was isolated from tissue of two patients with hepatocellular carcinoma developed on the background of a chronic hepatitis B virus infection. For identification and characterization of 3' ends of X gene open reading frame (ORF)-related transcripts, RNA was reverse transcribed into cDNA and subjected to polymerase chain reaction. Cloned amplification products from tumor tissue of one patient represented an approximately even distribution of transcripts terminating at the established poly(A) signal (standard transcripts) and of truncated transcripts terminating at a CATAAA poly(A) signal within the 3' end region of X gene ORF (truncated transcripts). Amplified cDNA from tumor tissue of the second patient could be attributed mainly to the standard type of transcripts, whereas cDNA from the nontumor tissue of the same patient could be assigned to four groups of transcripts: (i) standard transcripts, (ii) transcripts with internal deletions affecting the 3' end of the X gene, (iii) truncated transcripts, and (iv) hybrid transcripts displaying 5' sequences from the X gene ORF fused to cellular sequences.
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PMID:Diversity of hepatitis B virus X gene-related transcripts in hepatocellular carcinoma: a novel polyadenylation site on viral DNA. 164 31

Gene transcription rates and mRNA levels of plasminogen activator inhibitor type 2 (PAI-2) are markedly induced by the tumor promoting agent phorbol 12-myristate 13-acetate (PMA) in human HT1080 fibrosarcoma cells. To identify promoter elements required for basal-, and phorbol ester-inducible expression, deletion mutants of the PAI-1 promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene, were transiently expressed in HT1080 cells. Constitutive CAT activity was expressed from constructs containing more than 215 bp of promoter sequence, whereas deletion to position -91 bp abolished CAT gene expression. Treatment of transfected cells with PMA resulted in a three- to ten-fold increase in CAT expression from all constructs except from the construct shortened to position -91. DNAse1 protection analysis of the promoter region between -215 and the transcription initiation site revealed numerous protected regions, including two AP1-like binding sites (AP1a and AP1b) and one CRE-like element. Site-directed mutagenesis of the AP1a site or of the CRE-like site resulted in the loss of basal CAT activity and abolished the PMA effect, whereas mutagenesis of AP1b only partially inhibited basal and PMA-mediated expression. Our results suggest that the PAI-2 promoter contains at least two elements required for basal gene transcription and PMA-mediated induction.
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PMID:Regulatory elements involved in constitutive and phorbol ester-inducible expression of the plasminogen activator inhibitor type 2 gene promoter. 165 Apr 54

Retinoic acid and its analogs, retinoids, have been shown to be useful in the treatment of several types of tumors. Retinoids elicit their biological activities by binding to their specific nuclear receptors, denoted as RAR-alpha, beta and gamma. RAR's have been established to be retinoid-dependent transcription factors which belong to the steroid/thyroid nuclear receptor superfamily. Recently, retinoic acid has been reported to be extremely effective in the treatment of acute promyelocytic leukemia (APL) giving more than 70% complete remission efficiency. APL has been characterized by the specific chromosomal translocation, t(15;17). Analysis of the t(15;17) breaking point revealed that (i) either RAR-alpha on chromosome 17 or the gene named myl on chromosome 15 is abnormal in APL cells, and (ii) the abnormal fused protein myl/RAR-alpha is expressed, which is suspected to cause the APL. Thus, RAR-alpha gene may be now regarded as one of tumor suppressor genes.
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PMID:[Retinoids and acute promyelocytic leukemia]. 165 89

For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.
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PMID:Human monoclonal antibody against a tissue polypeptide antigen-related protein from a patient with a signet-ring cell carcinoma of the stomach. 169 68

A new combination of fluorescent dyes (rhodamine 123 and hydroethidine) was used to internally label hybridoma fusion partners. Murine hybridoma 520C9 (recognizing human c-erbB-2) was labeled with hydroethidine. Murine hybridoma 3G8 (recognizing human Fc gamma receptor III) was labeled with rhodamine 123, and verapamil was used to block rhodamine efflux via P-glycoprotein. Viability assays showed little cytotoxicity from these dyes at the concentrations used. The labeled cells were fused with polyethylene glycol, sorted for dual fluorescence on an Epics V cell sorter, and cloned. Hybrid hybridomas producing bispecific antibodies were selected for ability to promote lysis of SK-Br-3 breast cancer cells by human mononuclear cells. Several positive clones were obtained and shown to have a double content of DNA. Bispecific antibody produced by subclone 2B1 was purified by anion exchange chromatography and shown to bind both tumor cells and Fc gamma R III bearing cells. Using two parameter flow cytometric analysis, we were able to measure a 'bridging' effect of this bispecific antibody, which caused formation of complexes between PMNs and SK-Br-3 cells. Either parental antibody could compete with bispecific antibody to block such complexing. This fusion method provides several advantages over other techniques presently used (speed, convenience, low toxicity and automatic exclusion of dead cells) and can be applied to produce other hybrid hybridomas.
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PMID:Selection of hybrid hybridomas by flow cytometry using a new combination of fluorescent vital stains. 171 68

Chimeric proteins composed of acidic fibroblast growth factor (acidic FGF) and several forms of Pseudomonas exotoxin (PE) that cannot bind to the PE receptor have been produced in Escherichia coli by expressing chimeric genes in which DNA encoding acidic FGF is fused to various mutant forms of PE. These acidic FGF-PE fusion proteins were found to be cytotoxic to a variety of tumor cell lines including hepatocellular (PLC/PRF/5 and HEPG2), prostatic (LNCaP), colon (HT29), and breast (MCF-7) carcinomas at concentrations of 1-70 ng/ml. The cytotoxic effects of acidic FGF-PE were FGF-receptor specific as demonstrated by competition with excess acidic FGF and by showing that acidic FGF-PE bound to the FGF receptor with the same affinity as acidic FGF. Furthermore, the cell-killing activity of acidic FGF-PE was toxin-mediated, as an acidic FGF-PE mutant, which does not possess ADP-ribosylation activity, failed to kill cells. These findings demonstrate that acidic FGF-PE is a potent cytotoxic molecule that can be targeted to FGF receptor-bearing cells. Because acidic FGF is a potent angiogenic molecule, cytotoxic acidic FGF-PE chimeras may have utility as anti-angiogenic agents. These molecules could be helpful in determining the functional role of FGF receptors in cellular processes.
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PMID:Cytotoxic activity of chimeric proteins composed of acidic fibroblast growth factor and Pseudomonas exotoxin on a variety of cell types. 171 36

Basic fibroblast growth factor (bFGF) is a potent angiogenic mitogen. To elucidate the effect of bFGF inhibitors in vivo, anti-bFGF immunoneutralizing monoclonal antibody was prepared. One monoclonal antibody against human bFGF, obtained by cell fusion and designated 3H3, completely inhibited bFGF-induced proliferation of human umbilical vein endothelial cells at a concentration of 100 ng/ml. 3H3 did not bind to acidic fibroblast growth factor or HST1 protein, indicating high specificity for bFGF. Furthermore, the immunoneutralizing activity of 3H3 was examined in vivo. K1000 cells (a BALB/c 3T3 transformant in which the leader sequence-fused bFGF gene was transfected) were transplanted s.c. into BALB/c nude mice. Growth of the tumor cells was inhibited by i.v. treatment with 3H3 at a concentration of 200 micrograms/mouse. Histological observation showed that the antitumor effect of 3H3 was due to the inhibition of bFGF-induced angiogenesis. This experiment provides direct causal evidence for the hypothesis that tumor growth is angiogenesis dependent. This finding could also have implications for the development of novel therapeutic approaches to angiogenic solid tumors.
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PMID:Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor. 171 97

Ataxia-telangiectasia (A-T) is inherited as an monogenetic autosomal recessive disease. Ataxia appears around 1 year of age and progresses until the patient becomes wheelchair-bound, usually by age 10. This progress correlates with deterioration of Purkinje cells in the cerebellum. Sinopulmonary infections are common in patients from some countries but not others. One-third of the patients develop a neoplasm, usually lymphoid, sometime during their shortened lives. Conventional doses of radiation therapy for such cancers are contraindicated since A-T patients are hypersensitive to ionizing radiation. Five complementation groups have been described, based on correction of radioresistant DNA synthesis of fused fibroblasts from pairs of patients. Chromosomal translocations are found in 5-10% of peripheral T cells from most patients and the translocation breakpoints involve sites of normal somatic DNA rearrangement. Thus, the A-T gene(s) effects several cell lineages, suggesting that it is a "housekeeping" gene. Other speculations on "candidate genes" are considered. Recent progress localizing A-T to chromosome 11q23 is reviewed.
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PMID:Speculations on the ataxia-telangiectasia defect. 171 44


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