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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the three human retinoic acid receptors, RAR-beta, maps to a region on the short arm of chromosome 3 frequently deleted in lung cancer. Because retinoic acid is required for normal epithelial cell growth and regulation, and loss of a retinoic acid receptor might be expected to contribute to oncogenesis, we examined RAR-beta RNA and DNA in normal lung, 33 lung cancer cell lines and nine primary lung tumors. Normally, RAR-beta is expressed as two transcripts, of sizes 3.1 kb and 2.8 kb, which are strongly induced by retinoic acid. At least 50% of the cell lines and 30% of the tumor samples show altered RAR-beta expression and/or inducibility, including examples of absence or specific loss of one of the RAR-beta transcripts. Abnormalities in the expression patterns of RAR-alpha and RAR-gamma also are found, but at a lower frequency than RAR-beta abnormalities. Southern analysis reveals alteration of the RAR-beta gene in three of the cell lines. Our data suggest that abnormalities in structure and expression of the RAR-beta gene may be involved in the pathogenesis of lung cancer.
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PMID:High frequency of retinoic acid receptor beta abnormalities in human lung cancer. 171 24

A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N-methyl-N-nitrosourea or 7,12-dimethylbenz(a)anthracene; hamster lung carcinoma induced by N-methyl-N-nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: beta-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies).
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PMID:Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. 240 15

The role of nutrients in cancer causation has been a subject of considerable interest, research, and public discussion in recent years. Results from epidemiologic, clinical, and animal studies have suggested that: 1) a reduction in total calories decreases risk for a number of tumor types; 2) dietary protein is directly correlated with liver, prostate, and colon cancer, among others, with increasing dietary protein increasing the risk; 3) increased dietary fat is correlated with increased risk for breast cancer; the evidence for an effect of fat on colon cancer is equivocal in human and animal studies; 4) a deficiency of vitamin A may enhance lung and colon tumors in animal experiments but in human this is equivocal. Increasing vitamin A above normal levels, as an anticarcinogenic effect, has not been satisfactorily demonstrated in animal models. The synthetic retinoid, 13-cis retinoic acid, inhibits both colon and lung cancer in animal models; 5) zinc deficiency is associated with enhanced esophageal cancer in humans and markedly enhances animal tumors; selenium inhibits this form of neoplasia in animals, 6) diets low in lipotropes enhance liver cancer induced by a variety of hepatocarcinogens. Our data from studies in animal models agree in some cases with epidemiological observations, but disagree with others, particularly fat and colon cancer. Overall, some forms of cancer are enhanced by excessive calories, increased dietary protein and fat, and by deficiencies of vitamin A, selenium, zinc, and lipotropes. Decreasing total intake of calories, protein, and fat, and ensuring adequate dietary levels of vitamin A, selenium, zinc, and lipotropes decreases risk for some forms of cancer.
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PMID:The role of nutrients in cancer causation. 243 54

The modulation of clonal growth of cells of 15 human lung cancer lines was examined by coculture with different recombinant lymphokines, monokines, and several agents which induce differentiation in other malignant cell systems. Recombinant human tumor necrosis factor alpha (TNF) was inhibitory to all non-small cell lung cancer cell lines with a 50% effective dose of clonal inhibition (ED50) in the range of 30-2000 units/ml. Two representative squamous lines (SK-MES and P3) had 150 to 250 high affinity (Kd approximately equal to pM) cell surface TNF receptors. In contrast, clonal growth of small cell lung cancer lines was not inhibited by TNF, and two representative lines (H69c and R592) expressed negligible cell surface TNF receptors. Recombinant alpha, beta, and gamma interferons (4000 units/ml) each inhibited greater than or equal to 30% clonal growth of more than 50% of the non-small cell lung cancer lines. TNF (100-1000 units/ml) in combination with gamma-interferon was synergistic in the inhibition of clonal growth of these cells. Further studies showed that synergism of clonal inhibition occurred even when the cells were initially exposed to gamma-interferon, washed, and plated in soft agar with TNF. All-trans-retinoic acid (ED50, 5 X 10(-7)-10(-6) M), dimethyl sulfoxide (ED50, 1.2-1.6%), and 12-O-tetradecanoylphorbol-13-acetate (ED50, 5 X 10(-8)-10(-10) M) inhibited clonal proliferation of 7 of 9, 7 of 9, and 8 of 9 non-small cell lung cancer lines, respectively. In contrast, clonal proliferation of cells of small cell lung cancer lines was decreased only slightly at almost all concentrations of each of the agents. Interleukin-1 and -2 and granulocyte-monocyte colony-stimulating factor had no effect on the clonal growth of any of the lung cancer lines. Our results suggest that TNF in combination with gamma-interferon may be therapeutically active for some patients with non-small cell lung cancer, but small cell lung cancer probably will be unresponsive to all the agents that we examined.
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PMID:Effect of recombinant monokines, lymphokines, and other agents on clonal proliferation of human lung cancer cell lines. 303 6

Human lung tumors from 28 patients were investigated by sucrose density analysis for the presence of cellular retinoic acid-binding proteins. In the tumor-free lung tissue and in most of the 20 squamous cell carcinoma and in 1 small cell carcinoma specimens tested no specific binding of retinoic acid was detectable, whereas these binding proteins were observed in 5 adeno- and 1 large cell carcinoma. The amount of retinoic acid-binding protein was slightly increased in 1 bronchial adenoma considered to be a semimalignant tumor. These findings suggest that the occurrence of retinoic acid-binding proteins within lung carcinomas may be related to the histological type of lung cancer. Thus, the antineoplastic effects of retinoic acid suspected to be mediated by specific binding proteins are not generally to be expected on lung cancer.
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PMID:Relationship between cellular retinoic acid-binding protein and histology of human lung tumors. 609 82

Cellular retinoic acid-binding protein (CRABP) was detected in the cytosol of 11 human non-small-cell lung cancer specimens. Neither normal lung nor a small-cell lung cancer specimen contained this binding protein. The quality of CRABP per milligram of cytosol protein ranged from 48.3 to 426.5 fmol.
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PMID:Cellular retinoic acid-binding protein in human lung carcinomas. 626 83

Pre-treatment of metastatic human lung cancer cell subline (PGCL3) with all trans retinoic acid (RA) resulted in inhibition of cell growth in vitro and invasion through the reconstituted basement membrane. RA was also noticed to inhibit the experimental metastatic ability of PGCL3. Data showed that 5/6, 3/6 and 2/6 of the nude mice developed lung colonization in the control, the 5 mumol/L and the 10 mumol/L RA treated PGCL3 cells respectively. Data from DNA-RNA dot blot hybridization further showed that the 10 mumol/L RA treated cells expressed high levels of the human tissue inhibitors of metalloproteinases (Timp-1 and Timp-2) in comparing to the untreated cells. These results may help to clarify the mechanism of RA-induced inhibition effect on tumor invasion and metastasis.
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PMID:[The inhibition effect of retinoic acid on the invasion and metastasis abilities of metastatic human lung cancer cell subline]. 772 Jan 13

Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer.
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PMID:Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer. 779

Retinoids, natural or synthetic derivatives of vitamin A, have been studied as cancer chemopreventive agents and as therapeutic agents in the treatment of solid tumors. Intensive clinical research has focused on the role of retinoids in preventing second primary tumors following head and neck or lung cancer. The frequent occurrence of second primary tumors in these areas provides clinical support for the hypothesis of field carcinogenesis. Based on evidence of its efficacy in reversing oral premalignancy, the synthetic retinoid 13-cis-retinoic acid (13cRA) was studied in a 1-year trial to prevent the incidence of new cancers in patients who had been treated for squamous cell carcinoma (SCC) of the head and neck. Second primary tumors developed in only 4% of 49 patients treated with 13cRA, as compared with 24% of 51 patients treated with placebo (P = .005). These findings have led to two ongoing large-scale trials of 13cRA in North America. One study, performed through the M.D. Anderson Cancer Center and its affiliated Community Clinical Oncology Program and the institutions of the Radiation Therapy Oncology Group (RTOG), will determine whether long-term administration of low-dose 13cRA will prevent second primary tumors following an initial head and neck cancer. Another intergroup study using a similar randomized double-blind design is being performed among patients who have undergone resection of a stage I non-small-cell lung cancer. In Europe, a large chemoprevention study called Euroscan is currently examining the efficacy of another retinoid, retinyl palmitate, in preventing second primary tumors following head and neck or lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retinoid chemoprevention of second primary tumors. 783 82

The effects of retinoic acid (RA) are mainly mediated by its nuclear receptors, the RA receptors (RARs) and retinoid X receptors (RXRs) that regulate target gene expression by binding to specific RA-response elements (RAREs). RAR beta is the best characterized RA-responsive gene. Due to the presence of a RARE (beta RARE) in its promoter, the expression of the RAR beta 2 is markedly increased in response to RA in most epithelial tissues, including lung. Recently, it was observed that the RAR beta gene is not expressed in a number of human lung cancer cell lines, suggesting a possible correlation between abnormal expression of the RAR beta gene and lung cancer development. In this study, we investigate the RA response in human lung cancer cell lines. Here we report that the expression of the RAR beta gene cannot be regulated by RA in the majority of human lung cancer cell lines examined, while the general response to RA is intact. The nonresponsiveness of the RAR beta gene results from different defects in the response mechanism. Interestingly, we find in some cell lines a differential responsiveness of the beta RARE such that the element is inactive in its natural promoter context but active when linked to the heterologous tk promoter. Importantly, we also observe that the presence of retinoid receptors is not sufficient for the induction of the RAR beta gene. This suggests that specific factors determine the RA responsiveness in the context of its natural promoter. Our observation that the RA nonresponsiveness of the RAR beta promoter is a common feature of human lung cancer cell lines suggests that balanced RAR beta expression is an essential feature for the maintenance of a normal state of lung tissue.
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PMID:A specific defect in the retinoic acid response associated with human lung cancer cell lines. 792 14


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